US Pat. No. 9,463,215

ROMIDEPSIN FORMULATIONS AND USES THEREOF

Celgene Corporation, Sum...

1. A formulation comprising romidepsin in a concentration of 1 mg/mL to 10 mg/mL, propylene glycol (PG), ethanol (EtOH) and
an acetate buffer, wherein said formulation is stable for at least 6 months at ambient temperature wherein the ratio of PG,
EtOH and the acetate buffer is 30% of PG, 30% of EtOH, and 40% of the acetate buffer, and wherein a pH of the formulation
is in a range from 4.0 to 4.5.
US Pat. No. 9,468,605

FORMULATIONS OF (+)-2-[1-(3-ETHOXY-4-METHOXYPHENYL)-2-METHYLSULFONYLETHYL]-4-ACETYLAMINOISOINDOLINE-1,3-DIONE

Celgene Corporation, Sum...

1. An immediate-release oral dosage form comprising about 10-30% by weight of apremilast, about 40-50% by weight of lactose,
about 20-30% by weight of cellulose, about 1-5% by weight of carboxymethyl cellulose, about 1-5% by weight of fumed silica
and about 0.1-2% by weight of magnesium stearate and about 1-5% by weight of a coat, wherein about 100% of said apremilast
is released in about 1 hour in an aqueous buffer solution of about pH 3 with a paddle speed of 75 rpm.
US Pat. No. 9,056,103

METHODS USING 3-(4-AMINO-1-OXO-1,3-DIHYDRO-ISOINDOL-2-YL)-PIPERIDINE-2,6-DIONE FOR TREATMENT OF CERTAIN LEUKEMIAS

Celgene Corporation, Sum...

1. A method of treating leukemia, which comprises administering to a patient having leukemia escalating doses of 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione,
or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein a starting dose is between about 1 mg per
day and about 10 mg per day, and a maximum dose is between about 10 mg per day wherein the 3-(4-amino-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione
or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof is administered for 21 days followed by seven days
rest in a 28 day cycle, and wherein the leukemia is chronic lymphocytic leukemia.

US Pat. No. 9,056,120

METHODS OF TREATING MYELODYSPLASTIC SYNDROMES WITH A COMBINATION THERAPY USING LENALIDOMIDE AND AZACITIDINE

Celgene Corporation, Sum...

1. A method of treating myelodysplastic syndrome, which comprises administering to a patient in need thereof about 1 mg to
about 25 mg per day of a compound having the formula:

or a pharmaceutically acceptable salt, solvate or stereoisomer thereof.

US Pat. No. 9,181,216

4?-O-SUBSTITUTED ISOINDOLINE DERIVATIVES AND COMPOSITIONS COMPRISING AND METHODS OF USING THE SAME

Celgene Corporation, Sum...

1. A compound of formula:
or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
Y is C?O or CH2; and

R1 is alkyl substituted with one or more groups selected from alkoxy, halo, carboxy, alkylaminocarbonyl, alkoxycarbonyl, nitro,
nitrile, haloalkyl, hydroxy, and alkylsulfonyl.

US Pat. No. 9,067,912

SYNTHESIS OF 3-(5-AMINO-2-METHYL-4-OXOQUINAZOLIN-3(4H)-YL)PIPERIDINE-2,8-DIONE

Celgene Corporation, Sum...

1. A method for preparing 3-(5-amino-2-methyl-4-oxoquinazolin-3(4H)-yl)piperidine-2,6-dione, or an enantiomer or a mixture
of enantiomers thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or polymorph thereof; comprising the step
of reducing 3-(2-methyl-5-nitro-4-oxoquinazolin-3(4H)-yl)piperidine-2,6-dione via transfer hydrogenation to form 3-(5-amino-2-methyl-4-oxoquinazolin-3(4H)-yl)piperidine-2,6-dione,
or an enantiomer or a mixture of enantiomers thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or polymorph
thereof.

US Pat. No. 9,101,579

INHIBITION OF DRUG RESISTANT CANCER CELLS

Celgene Corporation, Sum...

1. A method of treating melanoma in a patient by overcoming resistance of the melanoma cells to a serine/threonine protein
kinase B-Raf (B-Raf) kinase inhibitor, comprising administering to the melanoma patient a histone deacetylase (HDAC) inhibitor,
wherein the B-Raf kinase inhibitor is sorafenib, wherein the HDAC inhibitor is romidepsin, and wherein romidepsin is administered
to the patient after pretreatment with sorafenib.

US Pat. No. 9,272,035

METHODS AND COMPOSITIONS USING PDE4 INHIBITORS FOR THE TREATMENT AND MANAGEMENT OF AUTOIMMUNE AND INFLAMMATORY DISEASES

Celgene Corporation, Sum...

1. A method of treating rheumatoid arthritis, which comprises administering to a patient in need of such treatment a therapeutically
effective amount of a first active agent, wherein the first active agent is a compound of formula A:
or a pharmaceutically acceptable salt thereof, and a therapeutically effective amount of an additional active agent, wherein
the additional active agent is cyclosporine A.

US Pat. No. 9,480,676

USE OF PDE4 INHIBITORS AND COMBINATIONS THEREOF FOR THE TREATMENT OF CYSTIC FIBROSIS

Celgene Corporation, Sum...

1. A method of treating cystic fibrosis, which comprises administering to a patient in need of such treatment (i) a therapeutically
effective amount of a first active agent which is a compound of formula (III):

or a pharmaceutically acceptable salt, a pharmaceutically acceptable hydrate, a pharmaceutically acceptable solvate, a pharmaceutically
acceptable clathrate, or a pharmaceutically acceptable polymorph thereof, and (ii) a therapeutically effective amount of a
cystic fibrosis transmembrane conductance regulator potentiator, a therapeutically effective amount of a cystic fibrosis transmembrane
conductance regulator corrector, or a combination thereof.

US Pat. No. 9,447,070

5-SUBSTITUTED ISOINDOLINE COMPOUNDS

Celgene Corporation, Sum...

1. A compound of formula (I):

and pharmaceutically acceptable salts, solvates, and stereoisomers thereof, wherein:
X is CH2 or C?O;

Z is: (CH2)m, wherein m is 0 or 1; or NH;

R1 is halogen or (C1-C6)alkyl, itself optionally substituted with one or more halogen; and

R2 is hydrogen; halogen; or (C1-C6)alkyl, itself optionally substituted with one or more halogen.

US Pat. No. 9,283,207

METHODS OF USING (+)-2-[1-(3-ETHOXY-4-METHOXYPHENYL)-2-METHYLSULFONYLETHYL]-4-ACETYLAMINOISOINDOLINE-1,3-DIONE

Celgene Corporation, Sum...

1. A method of treating a disease or disorder selected from Crohn's Disease or ulcerative colitis, the method comprising administering
to a patient having a Crohn's Disease or ulcerative colitis a therapeutically effective amount of a compound which is stereomerically
pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, or a pharmaceutically
acceptable salt thereof.
US Pat. No. 9,266,858

SYNTHESIS OF 3-(5-AMINO-2-METHYL-4-OXOQUINAZOLIN-3(4H)-YL)PIPERIDINE-2,6-DIONE

Celgene Corporation, Sum...

1. A method for preparing 3-(2-methyl-5-nitro-4-oxoquinazolin-3(4H)-yl)piperidine-2,6-dione, or an enantiomer or a mixture
of enantiomers thereof; comprising the step of reacting 2-methyl-5-nitro-4H-benzo[d][1,3]oxazin-4-one with 3-aminopiperidine-2,6-dione
or a salt thereof, and 1-propanephosphonic acid cyclic anhydride in a solvent selected from the group consisting of an amide,
hexamethylphosphoramide, dimethyl sulfoxide, and sulfolane, or a mixture thereof, to form 3-(2-methyl-5-nitro-4-oxoquinazolin-3(4H)-yl)piperidine-2,6-dione.

US Pat. No. 9,119,854

METHODS FOR TREATING CANCER USING COMBINATION THERAPY

Celgene Corporation, Sum...

1. A method for treating a cancer, comprising administering an effective amount of a substituted quinazolinone compound of
formula (I):
and pharmaceutically acceptable salts, solvates, and stereoisomers thereof, wherein:
R1 is: halo; —(CH2)nOH; (C1-C6)alkyl, optionally substituted with one or more halo; (C1-C6)alkoxy, optionally substituted with one or more halo; or —(CH2)nNHRa, wherein Ra is: hydrogen; (C1-C6)alkyl, optionally substituted with one or more halo; —(CH2)n-(6 to 10 membered aryl); —C(O)—(CH2)n-(6 to 10 membered aryl) or —C(O)—(CH2)n-(6 to 10 membered heteroaryl), wherein the aryl or heteroaryl is optionally substituted with one or more of: halo; —SCF3; (C1-C6)alkyl, itself optionally substituted with one or more halo; or (C1-C6)alkoxy, itself optionally substituted with one or more halo; —C(O)—(C1-C8)alkyl, wherein the alkyl is optionally substituted with one or more halo; —C(O)—(CH2)n-(C3-C10-cycloalkyl); —C(O)—(CH2)n—NRbRc, wherein Rb and Rc are each independently: hydrogen; (C1-C6)alkyl, optionally substituted with one or more halo; (C1-C6)alkoxy, optionally substituted with one or more halo; or 6 to 10 membered aryl, optionally substituted with one or more of:
halo; (C1-C6)alkyl, itself optionally substituted with one or more halo; or (C1-C6)alkoxy, itself optionally substituted with one or more halo; —C(O)—(CH2)n—O—(C1-C6)alkyl; or —C(O)—(CH2)n-(6 to 10 membered aryl);

R2 is: hydrogen; —(CH2)nOH; phenyl; —O—(C1-C6)alkyl; or (C1-C6 alkyl, optionally substituted with one or more halo;

R3 is: hydrogen; or (C1-C6)alkyl, optionally substituted with one or more halo; and

n is 0, 1, or 2; or
a substituted quinazolinone compound of formula (II):
and pharmaceutically acceptable salts, solvates, and stereoisomers thereof, wherein:
R4 is: halo; —(CH2)nOH; (C1-C6)alkyl, optionally substituted with one or more halo; or (C1-C6)alkoxy, optionally substituted with one or more halo;

R5 is: hydrogen; —(CH2)nOH; —O—(C1-C6)alkyl, or (C1-C6)alkyl, optionally substituted with one or more halo;

R6 is: hydrogen; or (C1-C6)alkyl, optionally substituted with one or more halo; and

n is 0, 1, or 2; or
a substituted quinazolinone compound of formula (III):
and pharmaceutically acceptable salts, solvates, and stereoisomers thereof, wherein:
Rd is:

hydrogen;
(C1-C6)alkyl, optionally substituted with one or more halo;

—C(O)—(CH1-C8)alkyl, wherein the alkyl is optionally substituted with one or more halo;

—C(O)—(CH2)n—(C3-C10-cycloalkyl);

—C(O)—(CH2)n—NReRf, wherein Re and Rf are each independently:

hydrogen;
(C1-C6)alkyl, optionally substituted with one or more halo; or

(C1-C6)alkoxy, optionally substituted with one or more halo; or

—C(O)—(CH2)n—O—(C1-C6)alkyl;

R7 is: hydrogen; —(CH2)nOH; phenyl; —O—(C1-C6)alkyl; or (C1-C6)or alkyl, optionally substituted with one or more halo;

R8 is: hydrogen; or (C1-C6)alkyl, optionally substituted with one or more halo; and

n is 0, 1, or 2 in combination with an effective amount of N-(3-(5-fluoro-2-(4-(2-methoxyethoxy)phenylamino)pyrimidin-4-ylamino)phenyl)acrylamide,
or a pharmaceutically acceptable salt thereof, to a patient having a cancer.

US Pat. No. 9,801,868

5-SUBSTITUTED ISOINDOLINE COMPOUNDS

Celgene Corporation, Sum...

1. A method of treating or managing a disease or disorder which comprises administering to a patient in need of such treatment
or management a therapeutically effective amount of a compound of formula (I):

or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
X is CH2 or C?O;

Z is: (CH2)m, wherein m is 0 or 1; or NH;

R1 is halogen or (C1-C6)alkyl, itself optionally substituted with one or more halogen; and

R2 is hydrogen; halogen; or (C1-C6)alkyl, itself optionally substituted with one or more halogen; and

wherein the disease or disorder is cancer or a disorder associated with angiogenesis.
US Pat. No. 9,226,913

METHODS OF TREATING CANCER USING A COMBINATION OF AN IMMUNOMODULATORY COMPOUND AND AN ARTEMISININ OR A DERIVATIVE THEREOF

Celgene Corporation, Sum...

1. A method of treating cancer, wherein the method comprises administering 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione,
and administering artemisinin or a derivative thereof, wherein the cancer is breast, colon or lung cancer, wherein the artemisinin
derivative is artesunate or artemisone, and wherein the combination exhibits a synergistic effect.

US Pat. No. 9,227,954

ISOINDOLINE COMPOUNDS AND METHODS OF THEIR USE

Celgene Corporation, Sum...

1. A compound of Formula II:
or a pharmaceutically acceptable salt, prodrug, or stereoisomer thereof, wherein:
X is CH2;

m is an integer of 0, 1, 2, or 3;
R4 is C3-10 cycloalkyl, 5 to 10 membered heterocyclyl, 5 to 10 membered heteroaryl, or C0-4 alkyl-NR41R42; wherein the cycloalkyl, heterocyclyl, and heteroaryl are each optionally substituted with one or more halogen, C1-6 alkyl, —CO—NR43R44, —COOR45, or C0-4 alkyl-C6-10 aryl, wherein the aryl itself may be optionally substituted with one or more halogen; and

R41, R42, R43, R44 and R45 are each independently hydrogen or C1-6 alkyl.

US Pat. No. 9,101,622

METHODS FOR TREATING NEWLY DIAGNOSED MULTIPLE MYELOMA 3-(4-AMINO-1-OXO-1,3-DIHYDRO-ISOINDOL-2-YL)-PIPERIDINE-2,6-DIONE IN COMBINATION WITH DEXAMETHASONE

Celgene Corporation, Sum...

1. A method of treating multiple myeloma, which comprises administering in a 28 day cycle to a patient having multiple myeloma:
(a) about 1 to about 50 mg per day of a compound having the formula:
or a pharmaceutically acceptable salt, solvate or stereoisomer thereof for 21 consecutive days followed by seven consecutive
days of rest from administration of said compound, and (b) a therapeutically effective amount of dexamethasone during such
28 day cycle, wherein the patient has not received previous treatment for multiple myeloma.

US Pat. No. 9,045,417

ISOTOPOLOGUES OF ISOINDOLE DERIVATIVES

Celgene Corporation, Sum...

1. A compound of formula:

or a pharmaceutically acceptable salt thereof, wherein:
at least one of Y1-Y25 is a hydrogen that is isotopically enriched with deuterium, and the others of Y1-Y25 are non-enriched hydrogen atoms.

US Pat. No. 9,283,215

METHODS FOR TREATING MULTIPLE MYELOMA USING 4-(AMINO)-2-(2,6-DIOXO(3-PIPERIDYL))-ISOINDOLINE-1,3-DIONE IN COMBINATION WITH ANTIBODIES

Celgene Corporation, Sum...

1. A method of treating multiple myeloma, which comprises administering to a patient having multiple myeloma (a) about 1 to
about 5 mg per day of a compound having the formula:
or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, and (b) a therapeutically effective amount of an antibody,
wherein the compound is administered in one or more cycles, each of which comprises administering the compound for a period
of time followed by a period of rest, wherein the multiple myeloma is relapsed, refractory, or relapsed and refractory.

US Pat. No. 9,050,324

METHODS FOR TREATING AMYLOIDOSIS WITH 3-(4-AMINO-1-OXO-1,3-DIHYDROISOINDOL-2-YL)-PIPERIDINE-2,6-DIONE

Celgene Corporation, Sum...

1. A method of treating amyloidosis, which comprises administering to a patient having amyloidosis: (a) from about 1 mg to
about 50 mg per day of a compound having the formula:

or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, and (b) a therapeutically effective amount of dexamethasone.

US Pat. No. 9,101,621

METHODS FOR TREATING MULTIPLE MYELOMA WITH 3-(4-AMINO-1-OXO-1,3-DIHYDRO-ISOINDOL-2-YL)-PIPERIDINE-2,6-DIONE AFTER STEM CELL TRANSPLANTATION

Celgene Corporation, Sum...

1. A method of treating multiple myeloma, which comprises administering to a patient having multiple myeloma about 1 to about
50 mg per day of a compound having the formula:
or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein the patient has previously received stem cell
transplantation.

US Pat. No. 9,051,110

PACKAGING FOR MEDICINE FOR CLINICAL TRIALS OR COMMERCIAL USE

Celgene Corporation, Sum...

12. A kit for preparing a package for receiving a vial, the kit comprising:
an inner portion that is flat and is foldable into a first shape configured to receive the vial therein; and
an outer portion that is flat and is foldable into a second shape configured to removably receive the first shape of the inner
portion, the outer portion defining an opening in at least the second shape,

the inner portion having an area for receiving an identifying mark or label that is viewable via the opening when the inner
and outer portions respectively are folded into the first and second shapes and the first shape is disposed within the second
shape so as to form the package.

US Pat. No. 9,221,788

SALTS AND SOLID FORMS OF (S)-3-(4- (4-(MORPHOLINOMETHYL)BENZYL)OXY)-1-OXOISOINDOLIN-2-YL)PIPERIDINE-2,6-DIONE AND COMPOSITIONS COMPRISING AND METHODS OF USING THE SAME

Celgene Corporation, Sum...

1. A solid form comprising a salt, hydrate, or solvate of Compound (I-S):
wherein the solid form is crystalline, wherein the solid form
comprises Compound (I-S) and water, having an XRPD pattern comprising peaks at approximately 8.31, 11.80, and 17.37 degrees
2?;

comprises Compound (I-S) and THF, having an XRPD pattern comprising peaks at approximately 11.80, 20.89, and 22.16 degrees
2?;

comprises a besylate salt of Compound (I-S), having an XRPD pattern comprising peaks at approximately 19.07, 20.71, and 23.96
degrees 2?;

comprises a DMSO solvate of a besylate salt of Compound (I-S), having an XRPD pattern comprising peaks at approximately 16.88,
18.14, and 20.02 degrees 2?;

comprises a D-tartrate salt of Compound (I-S), having an XRPD pattern comprising peaks at approximately 17.00, 19.73, and
25.86 degrees 2?;

comprises a hemi D-tartrate salt of Compound (I-S), having an XRPD pattern comprising peaks at approximately 6.21, 12.91,
and 16.32 degrees 2?;

comprises a L-tartrate salt of Compound (I-S), having an XRPD pattern comprising peaks at approximately 6.27, 10.90, and 15.32
degrees 2?;

comprises a tosylate salt of Compound (I-S), having an XRPD pattern comprising peaks at approximately 9.77, 15.41, and 19.25
degrees 2?; or

comprises a (+) camphorsulfonic acid salt of Compound (I-S), having an XRPD pattern comprising peaks at approximately 9.05,
14.61, and 16.82 degrees 2?.

US Pat. No. 9,393,238

METHODS FOR TREATING NON-HODGKIN'S LYMPHOMA WITH 3-(4-AMINO-1-OXO-1,3-DIHYDRO-ISOINDOL-2-YL)-PIPERIDINE-2,6-DIONE IN COMBINATION WITH A SECOND ACTIVE AGENT

Celgene Corporation, Sum...

1. A method of treating non-Hodgkin's lymphoma, which comprises administering to a patient having non-Hodgkin's lymphoma about
1 to about 50 mg per day of a compound having the formula:
or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, and a therapeutically effective amount of a second
active agent wherein the non-Hodgkin's lymphoma is follicular lymphoma and the second active agent is an anticancer agent.

US Pat. No. 9,394,274

PROCESSES FOR THE PREPARATION OF 4-AMINO-2-(2,6-DIOXOPIPERIDIN-3-YL)ISOINDOLINE-1,3-DIONE COMPOUNDS

Celgene Corporation, Sum...

1. A process for preparing a compound of Formula (XII):

comprising the step of cyclizing a compound of Formula (III):

with thionyl chloride and pyridine in CH2Cl2,

wherein R1 is H, F, benzyl, (C1-C8)alkyl, (C2-C8)alkenyl, or (C2-C8)alkynyl,

wherein the reaction temperature is from about ?40° C. to about ?30° C. for about 3 hours.

US Pat. No. 9,365,538

POLYMORPHIC FORMS OF 3-(4-AMINO-1-OXO-1,3 DIHYDRO-ISOINDOL-2-YL)-PIPERIDINE-2,6-DIONE

Celgene Corporation, Sum...

1. A polymorphic mixture comprising less than 20% by weight amorphous 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione
and greater than 80% by weight of an unsolvated crystalline 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione
having an X-ray powder diffraction pattern comprising peaks at approximately 8, 14.5, 16, 17.5, 20.5, 24, and 26 degrees 2?.

US Pat. No. 9,249,121

SOLID FORMS OF 3-(5-AMINO-2-METHYL-4-OXO-4H-QUINAZOLIN-3-YL)-PIPERIDINE-2,6-DIONE, AND THEIR PHARMACEUTICAL COMPOSITIONS AND USES

Celgene Corporation, Sum...

1. A method of treating inhibiting TNF? in a patient suffering from a disease or disorder comprising administering to the
patient a solid form of 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione:
or a stereoisomer thereof, or a pharmaceutically acceptable salt, solvate, hydrate, co-crystal, or clathrate thereof; wherein
the disease or disorder is cancer, a disorder associated with angiogenesis, pain, macular degeneration or a related syndrome,
a skin disease, a pulmonary disorder, an asbestos-related disorder, a parasitic disease, an immunodeficiency disorder, a CNS
disorder, CNS injury, atherosclerosis or a related disorder, dysfunctional sleep or a related disorder, hemoglobinopathy or
a related disorder, or a TNF? related disorder; and wherein the solid form has an X-ray powder diffraction pattern comprising:
peaks at approximately 14.6° 2?, 15.6° 2?, 16.7° 2?, 21.9° 2? and 30.0° 2? as shown in FIG. 1;

peaks at approximately 10.6° 2?, 14.7° 2?, 19.1° 2? and 25.9° 2? as shown in FIG. 4;

peaks at approximately 10.8° 2?, 15.1° 2?, 25.1° 2? and 26.6° 2? as shown in FIG. 7;

peaks at approximately 16.7° 2?, 21.7° 2?, 21.9° 2? and 25.8° 2? as shown in FIG. 10;

peaks at approximately 7.3° 2?, 14.6° 2?, 22.0° 2?, 30.0° 2? and 37.0° 2? as shown in FIG. 13;

peaks at approximately 14.5° 2?, 15.7° 2?, 22.7° 2? and 29.9° 2? as shown in FIG. 16; or

peaks at approximately 8.6° 2?, 13.1° 2?, 20.5° 2? and 26.3° 2? as shown in FIG. 18;
when analyzed using Cu K? X-ray radiation at 1.54 Å.
US Pat. No. 9,134,325

RESISTANCE BIOMARKERS FOR HDAC INHIBITORS

Celgene Corporation, Sum...

1. A method for identifying a cancer patient with an increased likelihood of a positive clinical response to romidepsin therapy
comprising:
obtaining a tumor sample from the cancer patient;
detecting the presence of TSPYL5 expression in said sample;
quantifying a level of said TSPYL5 expression in said sample; and
administering a therapeutically effective amount of romidepsin upon a determination that TSPYL5 expression in said sample
is lower than a defined expression threshold.

US Pat. No. 9,125,884

METHODS FOR TREATING CANCERS USING ORAL FORMULATIONS OF CYTIDINE ANALOGS

Celgene Corporation, Sum...

1. A method for treating a subject having non-small cell lung cancer, wherein the method comprises orally administering to
the subject a pharmaceutical composition comprising 5-azacytidine, or a pharmaceutically acceptable solvate or hydrate thereof
and at least one pharmaceutically acceptable excipient, wherein the pharmaceutical composition comprising 5-azacytidine is
a tablet comprising about 100 mg, about 200 mg, about 300 mg, about 400 mg, about 500 mg, or about 600 mg of 5-azacytidine;
and the method further comprises administering at least one additional therapeutic agent comprising a platinum agent.

US Pat. No. 9,433,606

SOLID FORMS COMPRISING (+)-2-[1-(3-ETHOXY-4-METHOXYPHENYL)-2-METHYLSULFONYLETHYL]-4-ACETYLAMINOISOINDOLINE-1,3-DIONE, COMPOSITIONS THEREOF, AND USES THEREOF

Celgene Corporation, Sum...

1. A method of treating sarcoidosis, the method comprising administering to a patient having sarcoidosis a therapeutically
effective amount of a Form B crystal form of the compound of Formula (I):
which is enantiomerically pure, and which has an X-ray powder diffraction pattern comprising peaks at about 10.1, 13.5, 20.7,
and 26.9 degrees 2?.
US Pat. No. 9,393,255

PHARMACEUTICAL COMPOSITIONS OF CYTIDINE ANALOGS AND METHODS OF USE THEREOF

Celgene Corporation, Sum...

1. A liquid pharmaceutical composition comprising 5-azacytidine prepared by reconstituting with cold sterile water, which
is substantially free of impurities, wherein the liquid pharmaceutical composition is a suspension, wherein the cold sterile
water is at a temperature of less than about 8° C.

US Pat. No. 9,353,080

POLYMORPHIC FORMS OF 3-(4-AMINO-1-OXO-1,3 DIHYDRO-ISOINDOL-2-YL)-PIPERIDINE-2,6-DIONE

Celgene Corporation, Sum...

1. A polymorphic mixture comprising less than 20% by weight amorphous 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione
and greater than 80% by weight crystalline 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione dihydrate.

US Pat. No. 9,434,689

PROCESSES FOR THE PREPARATION OF ISOINDOLE COMPOUNDS AND ISOTOPOLOGUES THEREOF

Celgene Corporation, Sum...

1. A process for the preparation of an enantiomerically enriched or enantiomerically pure aminosulfone compound of Formula
(III):
or a salt stereoisomer, or isotopologue thereof, wherein:
R1 and R2 are each independently hydrogen, halogen, substituted or unsubstituted (C1-C6)alkyl, substituted or unsubstituted (C1-C6)alkoxy, (C3-C18)cycloalkyl, (C3-C6)cycloalkoxy, cyano, —CF3, (C3-C18)cycloalkyl-(C1-C6)alkoxy, or an isotopologue thereof;

R3 is (C1-C6)alkyl, or an isotopologue thereof;

Y1 is hydrogen or deuterium; and

Y2 and Y3 are both hydrogen or both deuterium;

wherein not all of Y1, Y2, and Y3 are hydrogen;
comprising the step of
(a) reducing an enamine of Formula (II):
or a salt or isotopologue thereof, via hydrogenation with hydrogen gas or deuterium gas, in a solvent, and in the presence
of (1) a metal catalyst and a chiral ligand or (2) a chiral metal catalyst/ligand complex to form an enantiomerically enriched
or enantiomerically pure aminosulfone of Formula (III), or a salt or isotopologue thereof, wherein deuterium gas or a solvent
containing exchangeable deuterium for proton-deuterium exchange or both is used.

US Pat. No. 9,096,573

6-, 7-, OR 8-SUBSTITUTED QUINAZOLINONE DERIVATIVES AND COMPOSITIONS COMPRISING AND METHODS OF USING THE SAME

Celgene Corporation, Sum...

1. A compound of formula (II):
or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
R7 is : halo; —(CH2)nOH; or

(C1-C6)alkoyl, optionally substituted with one or more halo; or

—(CH2)nNHRd, wherein Rd is:

hydrogen;
(C1-C6)alkyl, optionally substituted with one or more halo;

—(CH2)n—(6 to 10 membered aryl);

—C(O)—(CH2)n—(6 to 10 membered aryl) or —C(O)—(CH2)n—(6 to 10 membered heteroaryl), wherein the aryl or heteroaryl is optionally substituted with one or more of: halo; —SCF3; (C1-C6)alkyl, itself optionally substituted with one or more halo; or (C1-C6)alkoxy, itself optionally substituted with one or more halo;

—C(O)—(C1-C8)alkyl, wherein the alkyl is optionally substituted with one or more halo;

—C(O)—(CH2)n—(C3-C 10-cycloalkyl);

—C(O)—(CH2)n—NReRf, wherein Re and Rf are each independently:

hydrogen;
(C1-C6)alkyl, optionally substituted with one or more halo;

(C1-C6)alkoxy, optionally substituted with one or more halo; or

6 to 10 membered aryl, optionally substituted with one or more of:
halo; (Ci-C6)alkyl, itself optionally substituted with one or more halo; or (C1-C6)alkoxy, itself optionally substituted with one or more halo;

—C(O)—(CH2)n—(C1-C6)alkyl; or

—C(O)—(CH2)n—(CH2)n-(6 to 10 membered aryl);

R8 is: hydrogen; —(CH2)nOH; phenyl; —O—(Ci-C6)alkyl; or (C1-C6)alkyl, optionally substituted with one or more halo;

R9 is: hydrogen; or (C1-C6)alkyl, optionally substituted with one or more halo; and

n is 0, 1, or 2.

US Pat. No. 9,085,551

SOLID FORMS OF 3-(4-NITRO-1-OXISOINDOLIN-2-YL)PIPERIDINE-2,6-DIONE

Celgene Corporation, Sum...

1. A solid form of crystalline Form C of the compound of Formula (I):

having an X-ray powder diffraction pattern having peaks located at 3, 4, 5, 6, 7, or all of the following approximate peak
positions: 10.25±0.10, 13.01±0.10, 15.40±0.10, 20.56±0.10, 21.07±0.10, 24.84±0.10, 25.78±0.10, and 26.17±0.10 degrees 2?,

or a pharmaceutically acceptable salt, hydrate, or solvate thereof.

US Pat. No. 9,796,698

ISOINDOLINE COMPOUNDS AND METHODS OF THEIR USE

Celgene Corporation, Sum...

1. A compound of Formula IV:
or a pharmaceutically acceptable salt, solvate, prodrug, or stereoisomer thereof, wherein:
X is C(?O) or CH2;

n is an integer of 0 or 1;
R8 is hydrogen or halo; and

R9 is hydrogen, amino, or 5 to 10 membered heteroaryl or heterocyclyl;

with the proviso that when n is 0, R9 is not hydrogen.

US Pat. No. 9,187,417

PROCESSES FOR THE PREPARATION OF (S)-1-(3-ETHOXY-4-METHOXYPHENYL)-2-METHANESULFONYLETHYLAMINE

Celgene Corporation, Sum...

1. A process for preparing a compound of Formula (I):

or a pharmaceutically acceptable salt, hydrate, solvate, or polymorph thereof, wherein:
R is —CH(C1-C6alkyl)Ar or hydrogen;

R1 is C1-C6alkyl;

each of R2, R3, R4, R5, and R6 is at each occurrence independently hydrogen, halo, C1-C6alkyl, C1-C6alkoxy, —CF3, —CN or —NO2; and

Ar is aryl,
which comprises:
(a) coupling an optionally substituted benzonitrile with a dialkylsulfone;
(b) hydrolyzing the coupled product to afford a beta-ketosulfone;
(c) reacting the beta-ketosulfone with a chiral auxiliary to form a chiral enamine;
(d) reducing the chiral enamine to afford an N-protected aminosulfone; and
(e) optionally deprotecting the N-protected aminosulfone.

US Pat. No. 9,309,220

PROCESSES FOR THE PREPARATION OF (S)-3-(4- (4-(MORPHOLINOMETHYL)BENZYL)OXY)-1-OXOISOINDOLIN-2-YL)PIPERIDINE-2,6-DIONE AND PHARMACEUTICALLY ACCEPTABLE FORMS THEREOF

Celgene Corporation, Sum...

1. A process for preparing an enantiomerically enriched or enantiomerically pure compound of Formula (I):

or a pharmaceutically acceptable form thereof, comprising
(step_1.1) transforming an enantiomerically enriched or enantiomerically pure compound of Formula (II):

or a salt thereof, wherein
(i) Z1 is NHY, and Z2 is OR; or

(ii) Z1 is OR, and Z2 is NHY; wherein

R is substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroalkyl,
substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl,
substituted or unsubstituted aralkyl, or a suitable protecting group of a carboxy group; and

Y is hydrogen, or a suitable amino protecting group;
to an enantiomerically enriched or enantiomerically pure compound of Formula (III), or a salt thereof:

wherein
(i) Z3 is NHY, and Z4 is OH; or

(ii) Z3 is OH, and Z4 is NHY;

under conditions suitable for ester to acid transformation, wherein step 1.1 occurs in the presence of an acid;
(step 1.2) cyclizing the enantiomerically enriched or enantiomerically pure compound of Formula (III) to an enantiomerically
enriched or enantiomerically pure compound of Formula (I-a):


under conditions suitable for cyclization;
(step 1.3) where Y is an amino protecting group, deprotecting the enantiomerically enriched or enantiomerically pure compound
of Formula (I-a) to an enantiomerically enriched or enantiomerically pure compound of Formula (I) under conditions suitable
for deprotection; and

(step 1.4) optionally transforming the enantiomerically enriched or enantiomerically pure compound of Formula (I) to a pharmaceutically
acceptable salt thereof under conditions suitable for salt formation.

US Pat. No. 9,303,014

SYNTHESIS OF 3-(5-AMINO-2-METHYL-4-OXOQUINAZOLIN-3(4H)-YL)PIPERIDINE-2,6-DIONE

Celgene Corporation, Sum...

1. N-(3-(2,6-Dioxopiperidin-3-yl)-2-methyl-4-oxo-3,4-dihydroquinazolin-5-yl)formamide, or an enantiomer or a mixture of enantiomers
thereof; or a solvate, hydrate, or polymorph thereof.
US Pat. No. 9,468,664

ROMIDEPSIN FORMULATIONS AND USES THEREOF

Celgene Corporation, Sum...

1. A formulation comprising romidepsin in a concentration of 1 mg/mL to 10 mg/mL, propylene glycol (PG), ethanol (EtOH) and
a citrate buffer, wherein said formulation is stable for at least 6 months at ambient temperature wherein the ratio of PG,
EtOH and the citrate buffer is 70% of PG, 20% of EtOH, and 10% of the citrate buffer, and wherein a pH of the formulation
is in a range from 4.5 to 5.0.

US Pat. No. 9,408,831

METHODS FOR TREATING RESPIRATORY VIRAL INFECTION

Celgene Corporation, Sum...

1. A method of treating, ameliorating, or delaying the onset of one or more symptoms associated with or resulting from a respiratory
viral infection in a subject, comprising administering to the subject a compound, or a pharmaceutically acceptable salt, solvate,
hydrate, or stereoisomer thereof, wherein the compound is

and wherein the respiratory viral infection is influenza infection, rhinovirus infection, coronavirus infection, or paramyxovirus
infection.

US Pat. No. 9,365,640

METHODS FOR THE TREATMENT OF CANCER AND INFLAMMATORY DISEASES USING CEREBLON AS A PREDICTOR

CELGENE CORPORATION, Sum...

1. A method of selecting the group of cancer patients based on the level of CRBN expression within the cancer, wherein said
method comprises:
obtaining a biological sample of the cancer from the patient;
determining whether CRBN is present in the sample, wherein said determining is performed by contacting the cancer with an
isolated antibody that immunospecifically binds to an epitope in CRBN, wherein the epitope has the amino acid sequence SEQ
ID NO:1, and wherein the antibody comprises: (i) a heavy chain having the amino acid sequence depicted in SEQ ID NO:5 or 9,
or (ii) a light chain having the amino acid sequence depicted in SEQ ID NO:7 or 11;

diagnosing the patient as having a drug-sensitive cancer if a higher than baseline level of the CRBN is determined to be present
in the sample; and

administering a therapeutically effective amount of the drug to a patient diagnosed as having a drug-sensitive cancer;
wherein the cancer patients are multiple myeloma, non-Hodgkin's lymphoma, diffuse large B-cell lymphoma, melanoma or solid
tumor patients; and

wherein the drug is thalidomide, lenalidomide, pomalidomide or 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione,
a stereoisomer thereof, or a pharmaceutically acceptable salt, solvate, hydrate, co-crystal, clathrate, or polymorph thereof.

US Pat. No. 9,192,662

METHODS USING IMMUNOMODULATORY COMPOUNDS FOR MODULATING LEVEL OF CD59

Celgene Corporation, Sum...

1. A method of treating or managing a disease associated with CD59 deficiency comprising administering to a patient a therapeutically
effective amount of an immunomodulatory compound, wherein the immunomodulatory compound is 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione
or 4-amino-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione, and wherein the disease or disorder is paroxysmal nocturnal hemoglobinuria.
US Pat. No. 9,795,650

ROMIDEPSIN FORMULATIONS AND USES THEREOF

Celgene Corporation, Sum...

1. A method of treating peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL) in a subject comprising administering
to the subject a formulation comprising romidepsin in a concentration of 1 mg/mL to 10 mg/mL, propylene glycol (PG), ethanol
(EtOH) and a citrate buffer, wherein said formulation is stable for at least 6 months at ambient temperature, and wherein
the ratio of PG, EtOH and the citrate buffer in the formulation is 70% of PG, 20% of EtOH, and 10% of the citrate buffer,
and wherein a pH of the formulation is in a range from 4.5 to 5.0.

US Pat. No. 9,309,219

ARYLMETHOXY ISOINDOLINE DERIVATIVES AND COMPOSITIONS COMPRISING AND METHODS OF USING THE SAME

Celgene Corporation, Sum...

1. A method for inhibiting TNF-? secretion in a patient suffering from cancer, which comprises administering to the patient
a TNF-alpha secretion inhibitory effective amount of a compound of formula (I):

or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
X is C?O or CH2;

R1 is —Y—R3;

R2 is H or (C1-C6)alkyl;

Y is: 6 to 10 membered aryl optionally substituted with one or more halogen;
R3 is: —(CH2)n-aryl, —O—(CH2)n-aryl or —(CH2)n—O-aryl, wherein the aryl is optionally substituted with one or more: (C1-C6)alkyl, itself optionally substituted with one or more halogen; (C1-C6)alkoxy, itself substituted with one or more halogen; oxo; amino; carboxyl; cyano; hydroxyl; halogen; 6 to 10 membered aryl
or heteroaryl, optionally substituted with one or more (C1-C6)alkyl, (C1-C6)alkoxy or halogen; —CONH2; or —COO—(C1-C6)alkyl, wherein the alkyl may be optionally substituted with one or more halogen;

—(CH2)n-heterocycle, —O—(CH2)n-heterocycle or —(CH2)n—O-heterocycle, wherein the heterocycle is optionally substituted with one or more: (C1-C6)alkyl, itself optionally substituted with one or more halogen; (C1-C6)alkoxy, itself substituted with one or more halogen; oxo; amino; carboxyl; cyano; hydroxyl; halogen; 6 to 10 membered aryl
or heteroaryl, optionally substituted with one or more (C1-C6)alkyl, (C1-C6)alkoxy or halogen; —CONH2; or —COO—(C1-C6)alkyl, wherein the alkyl may be optionally substituted with one or more halogen; or

—(CH2)n-heteroaryl, —O—(CH2)n-heteroaryl or —(CH2)n—O-heteroaryl, wherein the heteroaryl is optionally substituted with one or more: (C1-C6)alkyl, itself optionally substituted with one or more halogen; (C1-C6)alkoxy, itself substituted with one or more halogen; oxo; amino; carboxyl; cyano; hydroxyl; halogen; 6 to 10 membered aryl
or heteroaryl, optionally substituted with one or more (C1-C6)alkyl, (C1-C6)alkoxy or halogen; —CONH2; or —COO—(C1-C6)alkyl, wherein the alkyl may be optionally substituted with one or more halogen; and

n is 0, 1, 2 or 3.

US Pat. No. 9,757,355

ORAL DOSAGE FORMS OF CYCLOPROPANECARBOXYLIC ACID {2-[(1S)-1-(3-ETHOXY-4-METHOXY-PHENYL)-2-METHANESULFONYL-ETHYL]-3-OXO-2,3-DIHYDRO-1H-ISOINDOL-4-YL}-AMIDE

Celgene Corporation, Sum...

1. An oral dosage form consisting of about 9% by weight of a compound of formula (I):
or a pharmaceutically acceptable salt thereof, about 34% by weight of mannitol, about 5% by weight of sodium croscarmellose,
about 1% by weight of calcium stearate and about 51% by weight of polyvinylpyrrolidone-vinylacetate copolymer.
US Pat. No. 9,498,472

METHODS USING 3-(4-AMINO-1-OXO-1,3-DIHYDRO-ISOINDOL-2-YL)-PIPERIDINE-2,6-DIONE FOR TREATMENT OF CERTAIN LEUKEMIAS

Celgene Corporation, Sum...

1. A method of treating acute myelogenous leukemia in a human, which comprises cyclically administering for 21 days followed
by seven days rest in a 28 day cycle to a human having acute myelogenous leukemia a therapeutically effective amount of 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione,
or a pharmaceutically acceptable salt or solvate thereof at an amount of about 1 mg/day to about 50 mg/day.

US Pat. No. 9,133,161

PROCESSES FOR PREPARING ISOINDOLINE-1,3-DIONE COMPOUNDS

Celgene Corporation, Sum...

1. A process for preparing a compound of Formula I:

or an enantiomer or a mixture of enantiomers thereof; or a pharmaceutically acceptable salt thereof;
comprising the step of reacting a compound of Formula Ia:

with 3-aminopiperidine-2,6-dione, or an enantiomer or a mixture of enantiomers thereof; or a salt thereof, in the presence
of triethylamine; to form the compound of Formula I;

wherein R1 is hydroxyl.

US Pat. No. 9,126,906

ASYMMETRIC SYNTHETIC PROCESSES FOR THE PREPARATION OF AMINOSULFONE COMPOUNDS

Celgene Corporation, Sum...

1. A process for preparing an enantiomerically enriched compound of Formula (I):

or a salt, solvate, isotopologue, or polymorph thereof, wherein R1 and R2 are each independently hydrogen, halogen, substituted or unsubstituted (C1-C6)alkyl, substituted or unsubstituted (C1-C6)alkoxy, (C3-C18)cycloalkyl, (C3-C6)cycloalkoxy, cyano, —CF3, or (C3-C18)cycloalkyl-(C1-C6)alkoxy, or an isotopologue thereof; and R3 is (C1-C6)alkyl, or an isotopologue thereof; comprising the step of reducing an enamine of Formula (II):


or a salt or isotopologue thereof, via hydrogenation in the presence of (1) a metal catalyst and a chiral ligand, or (2) a
chiral metal catalyst/ligand complex to form the compound of Formula (I) with an enantiomeric excess of at least 10%.

US Pat. No. 9,371,309

POLYMORPHIC FORMS OF 3-(4-AMINO-1-OXO-1,3 DIHYDRO-ISOINDOL-2-YL)-PIPERIDINE-2,6-DIONE

Celgene Corporation, Sum...

1. A polymorphic mixture comprising less than 20% by weight amorphous 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione
and greater than 80% by weight of crystalline 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione hemihydrate.
US Pat. No. 9,611,465

PHARMACEUTICAL COMPOSITION CONTAINING CORE FACTOR INVOLVED IN PROLIFERATION AND DIFFERENTIATION OF CENTRAL NERVOUS CELL

CELGENE CORPORATION, Sum...

1. A method for screening for a therapeutic drug for a disease of cerebral cortex or a surgical injury of cerebral cortex,
comprising:
contacting a test substance with a ubiquitin ligase complex comprising cereblon (CRBN);
measuring a ubiquitin ligase activity of the ubiquitin ligase complex;
selecting the test substance that increased the ubiquitin ligase activity of the ubiquitin ligase complex as compared with
a ubiquitin ligase activity of the ubiquitin ligase complex without contacting the test substance; and

identifying the substance as a potential therapeutic drug for a disease of cerebral cortex or a surgical injury of cerebral
cortex.

US Pat. No. 9,550,766

ISOINDOLINE COMPOUNDS AND METHODS OF THEIR USE

Celgene Corporation, Sum...

1. A compound of Formula III:

or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
X is C(?O) or CH2;

m is an integer of 0, 1, 2, or 3;
R5 and R6 are each independently: hydrogen, halo, C1-6 alkyl, oxo, —NO2, C1-6 alkoxy, —Z—C1-6 alkyl, C0-6 alkyl-(5 to 10 membered heteroaryl), C0-6 alkyl-(5 to 6 membered heterocyclyl), C0-6 alkyl-OH, C0-4 alkyl-NH2, —NHCO—C1-6 alkyl, —OR21, or —(CH2—Y)0-2-(5 to 10 membered heteroaryl),

wherein Z is S or SO2;

wherein R21 is as defined above;

wherein each heteroaryl and heterocyclyl above is optionally substituted with one or more C1-6 alkyl; and

wherein the alkyl or alkoxy above may be optionally substituted with one or more: halogen; cyano; nitro; amino; C1-6 alkylidenedioxy; C1-6 alkoxy, itself optionally substituted with one or more halogens; or C1-6 alkylthio, itself optionally substituted with one or more halogens;

R7 is —COR71 or —PO(OR72)(OR73);

R71 is C1-10 alkyl, C6-10 aryl, or 5 to 6 membered heterocyclyl; wherein the alkyl, aryl, heterocyclyl may be optionally substituted with one or more
amino, C1-6 alkylamino, di(C1-6 alkyl)amino, or —COOR74; and

R72, R73, and R74 are each independently hydrogen or C1-10 alkyl.

US Pat. No. 9,387,195

METHODS FOR TREATING DISEASES USING ISOINDOLINE COMPOUNDS

Celgene Corporation, Sum...

1. A method of treating alopecia areata in a human, which comprises administering to a patient having alopecia areata a therapeutically
effective amount of a compound which is (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione,
or a pharmaceutically acceptable salt or solvate thereof, substantially free of its (?)-enantiomer.

US Pat. No. 9,586,929

6-, 7-, OR 8-SUBSTITUTED QUINAZOLINONE DERIVATIVES AND COMPOSITIONS COMPRISING AND METHODS OF USING THE SAME

Celgene Corporation, Sum...

1. A compound of formula (VI):

or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
R18 is: halo; —(CH2)nOH; (C1-C6)alkyl, optionally substituted with one or more halo;

(C1-C6)alkoxy, optionally substituted with one or more halo; or —(CH2)nNHRm, wherein Rm is:

hydrogen;
(C1-C6)alkyl, optionally substituted with one or more halo;

—(CH2)n-(6 to 10 membered aryl);

—C(O)—(CH2)n-(6 to 10 membered aryl) or —C(O)—(CH2)n-(6 to 10 membered heteroaryl), wherein the aryl or heteroaryl is optionally substituted with one or more of: halo; —SCF3; (C1-C6)alkyl, itself optionally substituted with one or more halo; or (C1-C6)alkoxy, itself optionally substituted with one or more halo;

—C(O)—(C1-C8)alkyl, wherein the alkyl is optionally substituted with one or more halo;

—C(O)—(CH2)n-(C3-C10-cycloalkyl);

—C(O)—(CH2)n—NRnRo, wherein Rn and Ro are each independently:

hydrogen;
(C1-C6)alkyl, optionally substituted with one or more halo;

(C1-C6)alkoxy, optionally substituted with one or more halo; or

6 to 10 membered aryl, optionally substituted with one or more of: halo; (C1-C6)alkyl, itself optionally substituted with one or more halo; or (C1-C6)alkoxy, itself optionally substituted with one or more halo;

—C(O)—(CH2)n—O—(C1-C6)alkyl; or

—C(O)—(CH2)n—O—(CH2)n-(6 to 10 membered aryl);

R19 is: hydrogen; —(CH2)nOH; phenyl; —O—(C1-C6)alkyl; or (C1-C6)alkyl, optionally substituted with one or more halo;

R20 is: hydrogen; or (C1-C6)alkyl, optionally substituted with one or more halo; and n is 0, 1, or 2.

US Pat. No. 9,532,977

CONTROLLED RELEASE ORAL DOSAGE FORMS OF POORLY SOLUBLE DRUGS AND USES THEREOF

Celgene Corporation, Sum...

1. A controlled release oral dosage form comprising:
(i) a compound of formula (I):
or a pharmaceutically acceptable polymorph, solvate or hydrate thereof, in an amount of about 10% by weight;
(ii) sodium carboxymethyl cellulose in an amount of about 34.5% by weight;
(iii) poly(butyl methacylate-co-2-dimethylaminoethyl methacrylate-co-methyl methacrylate) (1:2:1) in an amount of about 5%
by weight;

(iv) sodium alginate in an amount of about 19% by weight;
(v) sodium bicarbonate in an amount of about 5% by weight;
(vi) citric acid in an amount of about 8% by weight;
(vii) croscarmellose sodium in an amount of about 5% by weight;
(viii) magnesium stearate in an amount of about 1.5% by weight;
(ix) mannitol in an amount of about 11.5% by weight and
(x) silicon dioxide in an amount of about 0.5% by weight.
US Pat. No. 9,539,303

TREATMENT OF RAS-EXPRESSING TUMORS

Celgene Corporation, Sum...

1. A method of treating a Ras-expressing tumor comprising the steps of administering to a subject suffering from the Ras-expressing
tumor:
a) a therapeutically effective amount of romidepsin; and
b) a therapeutically effective amount of gemcitabine;
wherein the Ras-expressing tumor is a blood borne tumor selected from the group consisting of leukemia, multiple myeloma,
and myelodysplastic syndrome.

US Pat. No. 9,642,836

ISOTOPOLOGUES OF ISOINDOLE DERIVATIVES

Celgene Corporation, Sum...

1. A method of treating arthritis, osteoarthritis, inflammatory bowel disease, ankylosing spondylitis, rosacea, acne, pain,
sarcoidosis, psoriasis, dermatitis, or chronic obstructive pulmonary disease, comprising administering to a patient a compound
which is:

or a pharmaceutically acceptable salt thereof, wherein:
at least one of Y1-Y25 is a hydrogen that is isotopically enriched with deuterium, and the others of Y1-Y25 are non-enriched hydrogen atoms.

US Pat. No. 9,586,897

PROCESSES FOR THE PREPARATION OF (S)-1-(3-ETHOXY-4-METHOXYPHENYL)-2-METHANESULFONYLETHYLAMINE

Celgene Corporation, Sum...

1. A compound of Formula (III):

or a pharmaceutically acceptable salt, hydrate, or solvate thereof, wherein:
R1 is C1-C6alkyl;

R5 is —OCH2CH3; and

each of R2, R3, R4, and R6 is at each occurrence independently hydrogen, halo, C1-C6alkyl, C1-C6alkoxy, —CF3, —CN or —NO2.

US Pat. No. 9,518,094

ROMIDEPSIN SOLID FORMS AND USES THEREOF

Celgene Corporation, Sum...

1. A crystalline form of romidepsin characterized by:
XRPD characteristic peaks at about 9.0 2?, 10.3 2?, 11.7 2?, and 20.4 2?;
a differential scanning calorimetry (DSC) thermogram having endotherm at ˜255° C.; or
a thermogravimetric analysis (TGA) thermogram exhibiting a weight loss of ˜10.9%.
US Pat. No. 9,724,330

METHODS OF USING (+)-2-[1-(3-ETHOXY-4-METHOXYPHENYL)-2-METHYLSULFONYLETHYL]-4-ACETYLAMINOISOINDOLINE-1,3-DIONE

Celgene Corporation, Sum...

1. A method of treating an autoimmune disease, the method comprising administering to a patient having the autoimmune disease
a therapeutically effective amount of stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl) -2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione.
US Pat. No. 9,587,281

CEREBLON ISOFORMS AND THEIR USE AS BIOMARKERS FOR THERAPEUTIC TREATMENT

CELGENE CORPORATION, Sum...

1. A method for determining whether a subject having a multiple myeloma is sensitive to a treatment with pomalidomide or a
pharmaceutically acceptable salt thereof, wherein said method comprises
(a) obtaining a multiple myeloma sample from the subject;
(b) determining the level of an isoform of CRBN in the multiple myeloma sample, the isoform of CRBN comprising a single exon
6 deletion and comprising exons 1-5 and 7-11;

(c) diagnosing the subject as being sensitive to the treatment with pomalidomide or a pharmaceutically acceptable salt thereof
if the isoform of CRBN was determined to be less than a baseline level in the multiple myeloma sample; and

(d) administering an effective amount of pomalidomide or a pharmaceutically acceptable salt thereof to the subject diagnosed
as being sensitive to the treatment with pomalidomide or a pharmaceutically acceptable salt thereof.

US Pat. No. 9,499,514

ANTIPROLIFERATIVE COMPOUNDS AND METHODS OF USE THEREOF

Celgene Corporation, Sum...

1. A compound of Formula I:
or an enantiomer or a mixture of enantiomers thereof, or a pharmaceutically acceptable salt, solvate, hydrate, co-crystal,
clathrate, or polymorph thereof, wherein:
R1 is optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl or optionally substituted
heterocyclyl;

R2 and R3 are each halo;

where the substituents on R1, when present, are one to three groups Q, where each Q is independently alkyl, halo, haloalkyl, alkoxyalkyl, oxo, hydroxyl,
alkoxy, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally
substituted heterocyclylalkyl, optionally substituted aryl, optionally substituted heteroaryl, —R4OR5, —R4OR5—R4OR5, —R4N(R6)(R7), —R4SR5, —R4OR4N(R6)(R7), —R4OR4C(J)N(R6)(R7), —C(J)R9 or R4S(O)tR8;

each R4 is independently alkylene, alkenylene or a direct bond;

each R5 is independently hydrogen, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, aryl, heteroaryl, heterocyclyl or heterocyclylalkyl,
where alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, aryl, heteroaryl, heterocyclyl or heterocyclylalkyl groups
in R5 are each independently optionally substituted with 1-3 Q1 groups, where each Q1 is independently alkyl, haloalkyl or halo;

R6 and R7 are selected as follows:

i) R6 and R7 are each independently hydrogen or alkyl; or

ii) R6 and R7 together with the nitrogen atom on which they are substituted form a 5 or 6-membered heterocyclyl or heteroaryl ring, optionally
substituted with one or two halo, alkyl or haloalkyl;

R8 is alkyl, haloalkyl, or hydroxyalkyl;

R9 is alkyl or aryl;

J is O or S; and
t is 1 or 2.
US Pat. No. 9,782,451

ROMIDEPSIN FORMULATIONS AND USES THEREOF

Celgene Corporation, Sum...

1. A method of treating peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL) in a subject comprising administering
to the subject a formulation comprising romidepsin in a concentration of 1 mg/mL to 10 mg/mL, propylene glycol (PG), ethanol
(EtOH) and an acetate buffer, wherein said formulation is stable for at least 6 months at ambient temperature, and wherein
the ratio of PG, EtOH and the acetate buffer in the formulation is 30% of PG, 30% of EtOH, and 40% of the acetate buffer,
and wherein a pH of the formulation is in a range from 4.0 to 4.5.

US Pat. No. 9,695,145

PROCESSES FOR THE PREPARATION OF ISOTOPOLOGUES OF 3-(4-((4- MORPHOLINOMETHYL)BENZYL)OXY)-1-OXOISOINDOLIN-2-YL)PIPERIDINE-2,6-DIONE AND PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF

Celgene Corporation, Sum...

1. A compound of the formula:

or a pharmaceutically acceptable salt or solvate thereof, wherein:
at least one of Y1, Y2, Y3, Y4, Y5, Y6, Y7, Y8, Y9, Y10, Y11, Y12, Y13, Y14, Y15, Y16, Y17, Y18, Y19, Y20, Y21, Y22, Y23, Y24, Y25, Y26, and Y27 is a hydrogen that is isotopically enriched with deuterium, and the others of Y1, Y2, Y3, Y4, Y5, Y6, Y7, Y8, Y9, Y10, Y11, Y12, Y13, Y14, Y15, Y16, Y17, Y18, Y19, Y20, Y21, Y22, Y23, Y24, Y25, Y26, and Y27 are non-enriched hydrogen atoms, provided that the compound is not


US Pat. No. 9,695,146

SOLID FORMS COMPRISING 4-AMINO-2-(2,6-DIOXOPIPERIDINE-3-YL)ISOINDOLINE-1,3-DIONE AND A COFORMER, COMPOSITIONS AND METHODS OF USE THEREOF

Celgene Corporation, Sum...

1. A solid form comprising (a) 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione (pomalidomide); and (b) a coformer;
wherein
the coformer is gallic acid and the solid form has an X-ray powder diffraction (XRPD) pattern comprising peaks at 22.98, 26.16,
and 26.90 degrees 2?±0.2 degrees 2?;

the coformer is vanillin and the solid form has an XRPD pattern comprising peaks at 13.09, 17.30, and 25.61 degrees 2?±0.2
degrees 2?;

the coformer is cyclamic acid and the solid form has an XRPD pattern comprising peaks at 6.42, 7.88, and 15.73 degrees 2?±0.2
degrees 2?;

the coformer is D-glucose and the solid form has an XRPD pattern comprising peaks at 17.09, 20.68, and 25.52 degrees 2?±0.2
degrees 2?;

the coformer is propyl gallate and the solid form has an XRPD pattern comprising peaks at 7.78, 25.23, and 25.61 degrees 2?±0.2
degrees 2?;

the coformer is saccharin and the solid form has an XRPD pattern comprising peaks at 15.98, 19.09, and 25.10 degrees 2?±0.2
degrees 2?;

the coformer is sodium lauryl sulfate and the solid form has an XRPD pattern comprising peaks at 2.66, 5.30, and 7.93 degrees
2?±0.2 degrees 2?;

the coformer is magnesium bromide and the solid form has an XRPD pattern comprising peaks at 3.23, 28.76, and 29.95 degrees
2?±0.2 degrees 2?;

the coformer is malonic acid and the solid form has an XRPD pattern comprising peaks at 12.23, 16.63, and 25.58 degrees 2?±0.2
degrees 2?;

the coformer is maltol and the solid form has an XRPD pattern comprising peaks at 16.51, 17.09, and 25.73 degrees 2?±0.2 degrees
2?;

the coformer is methyl paraben and the solid form has an XRPD pattern comprising peaks at 18.73, 25.69, and 26.70 degrees
2?±0.2 degrees 2?; or

the coformer is zinc chloride and the solid form has an XRPD pattern comprising peaks at 2.38, 17.17, and 25.71 degrees 2?±0.2
degrees 2?.

US Pat. No. 9,629,849

SALTS AND SOLID FORMS OF (S)-3-(4-((4-(MORPHOLINOMETHYL)BENZYL)OXY)-1-OXOISOINDOLIN-2-YL)PIPERIDINE-2,6-DIONE AND COMPOSITIONS COMPRISING AND METHODS OF USING THE SAME

Celgene Corporation, Sum...

1. A method of treating cancer, an immune-related disease or disorder, an inflammatory disease or disorder, or a symptom thereof
in a subject, comprising administering to the subject a therapeutically effective amount of a solid form comprising a HCl
salt of Compound (I-S):
or a salt, hydrate, anhydrate, or solvate of the HCl salt, wherein the solid form is crystalline, wherein the solid form
is Form A crystal form characterized by an XRPD pattern comprising peaks at approximately 15.09, 15.94, and 22.30 degrees
2?;

is Form B crystal form characterized by an XRPD pattern comprising peaks at approximately 7.11, 14.20, and 20.71 degrees 2?;
is Form C crystal form characterized by an XRPD pattern comprising peaks at approximately 6.55, 13.14, and 13.37 degrees 2?;
is Form D crystal form characterized by an XRPD pattern comprising peaks at approximately 13.52, 14.16, and 25.00 degrees
2?;

is Form E crystal form characterized by an XRPD pattern comprising peaks at approximately 9.82, 17.06, and 17.73 degrees 2?;
is Form F crystal form characterized by an XRPD pattern comprising peaks at approximately 13.71, 14.22, and 20.87 degrees
2?;

is Form G crystal form characterized by an XRPD pattern comprising peaks at approximately 6.85, 20.20, and 20.60 degrees 2?;
is Form H crystal form characterized by an XRPD pattern comprising peaks at approximately 6.83, 20.19, and 20.58 degrees 2?;
is Form I crystal form characterized by an XRPD pattern comprising peaks at approximately 13.95, 23.39, and 24.10 degrees
2?;

is Form J crystal form characterized by an XRPD pattern comprising peaks at approximately 4.86, 13.48, and 20.06 degrees 2?;
or

is Form K crystal form characterized by an XRPD pattern comprising peaks at approximately 7.09, 14.03, and 14.22 degrees 2?;
wherein the cancer, immune-related disease or disorder, or inflammatory disease or disorder is lupus, scleroderma, Sjögren
syndrome, ANCA-induced vasculitis, anti-phospholipid syndrome, myasthenia gravis, systemic lupus erythematosus (SLE), cutaneous
lupus erythematosus (CLE), discoid lupus erythematosus (DLE), drug-induced lupus, or multiple myeloma.

US Pat. No. 9,624,271

ROMIDEPSIN SOLID FORMS AND USES THEREOF

Celgene Corporation, Sum...

1. Amorphous romidepsin, wherein the amorphous romidepsin is obtained from an isopropanol-trifluoroethanol/methanol mixture.
US Pat. No. 9,616,019

NANOSUSPENSION OF A POORLY SOLUBLE DRUG VIA MICROFLUIDIZATION PROCESS

Celgene Corporation, Sum...

1. A stable, aqueous suspension having an enhanced bioavailability consisting of:
particles of cyclopropyl-N-{2-[(1S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-3-oxoisoindoline-4-yl}carboxamide
having a mean particle size of less than 800 nm,

sodium lauryl sulfate (SLS) in a concentration of 0.2%, and
hydropropylmethylcellulose (HPMC) in a concentration of 0.5%,wherein said suspension is suitable for long term storage; andwherein said suspension has a relative exposure that is 147% of the exposure of the suspension in the absence of SLS.

US Pat. No. 9,682,952

ISOTOPOLOGUES OF 3-(5-AMINO-2-METHYL-4-OXOQUINAZOLIN-3(4H)-YL) PIPERIDINE-2-6-DIONE AND METHODS OF PREPARATION THEREOF

Celgene Corporation, Sum...

1. A compound of the formula:
or a pharmaceutically acceptable salt thereof, wherein:
at least one of Yl, Y2, Y3, Y4, Y6, Y7, Y8, Y9, Y10, Y11, Y12, Y13 and Y14 is a hydrogen that is isotopically enriched with deuterium, and the others of Y1, Y2, Y3, Y4, Y5, Y6, Y7, Y8, Y9, Y10, Y11, Y12, Y13 and Y14 are non-enriched hydrogen atoms.

US Pat. No. 9,662,321

METHODS FOR TREATING NEWLY DIAGNOSED MULTIPLE MYELOMA WITH 3-(4-AMINO-1-OXO-1,3-DIHYDROISOINDOL-2-YL)-PIPERIDINE-2,6-DIONE IN COMBINATION WITH SECOND ACTIVE AGENTS

Celgene Corporation, Sum...

1. A method of treating multiple myeloma, which comprises administering in a 28 day cycle to a patient having multiple myeloma:
(a) about 1 to about 50 mg per day of a compound having the formula:
or a pharmaceutically acceptable salt, solvate or stereoisomer thereof for 21 consecutive days followed by seven consecutive
days of rest from administration of the compound, (b) a therapeutically effective amount of dexamethasone during the 28 day
cycle, and (c) a therapeutically effective amount of a proteasome inhibitor during the 28 day cycle.

US Pat. No. 9,751,853

SOLID FORMS OF 3-(5-AMINO-2-METHYL-4-OXO-4H-QUINAZOLIN-3-YL)-PIPERIDINE-2,6-DIONE, AND THEIR PHARMACEUTICAL COMPOSITIONS AND USES

Celgene Corporation, Sum...

1. A method of treating or managing a disease or disorder comprising administering to a patient having the disease or disorder
a solid form comprising a hydrochloride salt of 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione:
having an X-ray powder diffraction pattern comprising peaks at approximately 8.6° 2?, 13.1° 2?, 20.5° 2? and 26.3° 2?, wherein
the disease or disorder is leukemia, lymphoma, myeloma, myelodysplastic syndrome, or myeloproliferative disease.
US Pat. No. 9,693,987

METHODS FOR TREATING CANCERS USING ORAL FORMULATIONS OF CYTIDINE ANALOGS

Celgene Corporation, Sum...

1. A method for treating a subject having non-small cell lung cancer, wherein the method comprises orally administering to
the subject a pharmaceutical composition comprising 5-azacytidine, or a pharmaceutically acceptable solvate or hydrate thereof
and at least one pharmaceutically acceptable excipient, wherein the pharmaceutical composition comprising 5-azacytidine is
a tablet; and the method further comprises administering at least one additional therapeutic agent comprising trastuzumab,
rituximab, bevacizumab, pertuzumab, tositumomab, edrecolomab, G250, gemtuzumab ozogamicin, alemtuzumab, or yttrium-90-ibritumomab
tiuxetan.

US Pat. No. 9,688,623

PROCESSES FOR THE PREPARATION OF (S)-1-(3-ETHOXY-4-METHOXYPHENYL)-2-METHANESULFONYLETHYLAMINE

Celgene Corporation, Sum...

1. A compound of Formula (IV):
or a pharmaceutically acceptable salt, hydrate, solvate, or polymorph thereof, wherein:
R is C1-C6alkyl;

R1 is C1-C6alkyl;

each of R2, R3, R4, R5, and R6 is at each occurrence independently hydrogen, halo, C1-C6alkyl, C1-C6alkoxy, —CF3, —CN or —NO2; and

Ar is aryl.
US Pat. No. 9,694,015

METHODS FOR THE TREATMENT OF LOCALLY ADVANCED BREAST CANCER

Celgene Corporation, Sum...

1. A method of treating or managing locally advanced breast cancer comprising administering to a patient in need of such treatment
or management a therapeutically effective amount of 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione, or
an enantiomer or mixture of enantiomers thereof; or a pharmaceutically acceptable salt, co-crystal, or clathrate thereof.

US Pat. No. 9,732,064

5-SUBSTITUTED QUINAZOLINONE DERIVATIVES AND COMPOSITIONS COMPRISING AND METHODS OF USING THE SAME

Celgene Corporation, Sum...

1. A method of treating a cancer characterized by enhanced TNF-? activity in a patient having the cancer, comprising administering
to the patient a compound of formula (III):

or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
Rd is:

hydrogen;
(C1-C6)alkyl, optionally substituted with one or more halo;

—C(O)—(C1-C8)alkyl, wherein the alkyl is optionally substituted with one or more halo;

—C(O)—(CH2)n—(C3-C10-cycloalkyl);

—C(O)—(CH2)n—NReRf, wherein Re and Rf are each independently:

hydrogen;
(C1-C6)alkyl, optionally substituted with one or more halo; or

(C1-C6)alkoxy, optionally substituted with one or more halo; or

—C(O)—(CH2)n—O—(C1-C6)alkyl;

R7 is: hydrogen; —(CH2)nOH; phenyl; —O—(C1-C6)alkyl; or (C1-C6)alkyl, optionally substituted with one or more halo;

R8 is: hydrogen; or (C1-C6)alkyl, optionally substituted with one or more halo; and

n is 0, 1, or 2; and
wherein the cancer is leukemia, lymphoma, myeloma, myelodysplastic syndrome, myeloproliferative disease, a cancer of skin,
a cancer of ovary, a cancer of prostate, a cancer of brain, a cancer of kidney, a cancer of pancreas, a cancer of bladder,
a cancer of head and neck, a cancer of liver, a cancer of lung, or a cancer of colon or rectum.

US Pat. No. 9,808,450

SOLID FORMS COMPRISING 3-(4-AMINO-1-OXO-1,3-DIHYDRO-ISOINDOL-2-YL)-PIPERIDINE-2,6-DIONE AND A COFORMER, COMPOSITIONS AND METHODS OF USE THEREOF

Celgene Corporation, Sum...

1. A crystalline solid form comprising (a) 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione, or a pharmaceutically
acceptable salt, solvate, hydrate, stereoisomer, prodrug, or clathrate thereof; and (b) a coformer; wherein the coformer is
benzoic acid, glycolic acid, hippuric acid, magnesium bromide, sodium lauryl sulfate, vanillic acid, or zinc chloride.

US Pat. No. 9,969,713

SOLID FORMS OF 3-(5-AMINO-2-METHYL-4-OXO-4H-QUINAZOLIN-3-YL)-PIPERIDINE-2,6-DIONE, AND THEIR PHARMACEUTICAL COMPOSITIONS AND USES

Celgene Corporation, Sum...

1. A method of treating or managing refractory or resistant multiple myeloma in a patient comprising administering to the patient a solid form comprising a hydrochloride salt of 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione:having an X-ray powder diffraction pattern comprising peaks at approximately 8.6°2?, 13.1°2?, 20.5°2? and 26.3°2?.

US Pat. No. 9,808,451

ANTIPROLIFERATIVE COMPOUNDS AND METHODS OF USE THEREOF

Celgene Corporation, Sum...

1. A pharmaceutical composition comprising a compound of Formula I:

or an enantiomer or a mixture of enantiomers thereof, or a pharmaceutically acceptable salt, solvate, or hydrate, thereof,
wherein:

R1 is optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl or optionally substituted
heterocyclyl;

R2 and R3 are each halo;

where the substituents on R1, when present, are one to three groups Q, where each Q is independently alkyl, halo, haloalkyl, alkoxyalkyl, oxo, hydroxyl,
alkoxy, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally
substituted heterocyclylalkyl, optionally substituted aryl, optionally substituted heteroaryl, —R4OR5, —R4OR5—R4OR5, —R4N(R6)(R7), —R4SR5, —R4OR4N(R6)(R7), —R4OR4C(J)N(R6)(R7), —C(J)R9 or R4S(O)tR8;

each R4 is independently alkylene, alkenylene or a direct bond;

each R5 is independently hydrogen, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, aryl, heteroaryl, heterocyclyl or heterocyclylalkyl,
where alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, aryl, heteroaryl, heterocyclyl or heterocyclylalkyl groups
in R5 are each independently optionally substituted with 1-3 Q1 groups, where each Q1 is independently alkyl, haloalkyl or halo;

R6 and R7 are selected as follows:

i) R6 and R7 are each independently hydrogen or alkyl; or

ii) R6 and R7 together with the nitrogen atom on which they are substituted form a 5 or 6-membered heterocyclyl or heteroaryl ring, optionally
substituted with one or two halo, alkyl or haloalkyl;

R8 is alkyl, haloalkyl, or hydroxyalkyl;

R9 is alkyl or aryl;

J is O or S; and
t is 1 or 2.
US Pat. No. 9,857,359

METHODS FOR DETERMINING DRUG EFFICACY USING CEREBLON-ASSOCIATED PROTEINS

CELGENE CORPORATION, Sum...

1. A method of assessing the efficacy of a compound in treating a disease or disorder, comprising:
(a) administering a compound to a subject having a disease or disorder;
(b) obtaining a first cell sample from the subject after administering the compound;
(c) determining the level of IKZF1 and/or IKZF3 in the first cell sample by measuring the protein level of IKZF1 and/or IKZF3;
and

(d) comparing the level of IKZF1 and/or IKZF3 from step (c) to the level of the same protein obtained from a reference cell
sample,

wherein a decrease in the level of IKZF1 and/or IKZF3 as compared to the reference is indicative of the efficacy of the compound
in treating the disease or disorder;

wherein the disease or disorder is a blood cancer; and
wherein the compound is thalidomide, lenalidomide, pomalidomide, 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione
or 3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, or a pharmaceutically acceptable salt-thereof.

US Pat. No. 9,834,538

6-, 7-, OR 8-SUBSTITUTED QUINAZOLINONE DERIVATIVES AND COMPOSITIONS COMPRISING AND METHODS OF USING THE SAME

Celgene Corporation, Sum...

1. A compound of formula (I):

or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
R1 is hydrogen;

R4 is halo; —(CH2)nOH; (C1-C6)alkyl, optionally substituted with one or more halo; (C1-C6)alkoxy, optionally substituted with one or more halo; or

—(CH2)nNHRa, wherein Ra is:

hydrogen;
(C1-C6)alkyl, optionally substituted with one or more halo;

—(CH2)n-(6 to 10 membered aryl);

—C(O)—(CH2)n-(6 to 10 membered aryl) or —C(O)—(CH2)n-(6 to 10 membered heteroaryl), wherein the aryl or heteroaryl is optionally substituted with one or more of: halo; —SCF3; (C1-C6)alkyl, said alkyl itself optionally substituted with one or more halo; or (C1-C6)alkoxy, said alkoxy itself optionally substituted with one or more halo;

—C(O)—(C1-C8)alkyl, wherein the alkyl is optionally substituted with one or more halo;

—C(O)—(CH2)n—(C3-C10-cycloalkyl);

—C(O)—(CH2)n—NRbRc, wherein Rb and Rc are each independently:

hydrogen;
(C1-C6)alkyl, optionally substituted with one or more halo;

(C1-C6)alkoxy, optionally substituted with one or more halo; or

6 to 10 membered aryl, optionally substituted with one or more of: halo;
 (C1-C6)alkyl, itself optionally substituted with one or more halo; or

 (C1-C6)alkoxy, itself optionally substituted with one or more halo;

—C(O)—(CH2)n—O—(C1-C6)alkyl; or

—C(O)—(CH2)n—O—(CH2)n-(6 to 10 membered aryl);

R2 and R3 together form a 5 or 6 membered ring, optionally substituted with one or more of:

halo; (C1-C6)alkyl, optionally substituted with one or more halo; and (C1-C6)alkoxy, optionally substituted with one or more halo;

R5 is: hydrogen; —(CH2)nOH; phenyl; —O—(C1-C6)alkyl; or (C1-C6)alkyl, optionally substituted with one or more halo;

R6 is: hydrogen; or (C1-C6)alkyl, optionally substituted with one or more halo; and

n is 0, 1, or 2.

US Pat. No. 9,884,062

SALTS AND SOLID FORMS OF (S)-3-(4-((4-(MORPHOLINOMETHYL)BENZYL)OXY)-1-OXOISOINDOLIN-2-YL)PIPERIDINE-2,6-DIONE AND COMPOSITIONS COMPRISING AND METHODS OF USING THE SAME

Celgene Corporation, Sum...

1. A method of treating cancer, an immune-related disease or disorder, an inflammatory disease or disorder, or a symptom thereof
in a subject, comprising administering to the subject a therapeutically effective amount of a solid form comprising a salt,
hydrate, or solvate of Compound (I-S):
wherein the solid form is crystalline, wherein the solid form
comprises Compound (I-S) and water, having an XRPD pattern comprising peaks at approximately 8.31, 11.80, and 17.37 degrees
2?;

comprises Compound (I-S) and THF, having an XRPD pattern comprising peaks at approximately 11.80, 20.89, and 22.16 degrees
2?;

comprises a besylate salt of Compound (I-S), having an XRPD pattern comprising peaks at approximately 19.07, 20.71, and 23.96
degrees 2?;

comprises a DMSO solvate of a besylate salt of Compound (I-S), having an XRPD pattern comprising peaks at approximately 16.88,
18.14, and 20.02 degrees 2?;

comprises a D-tartrate salt of Compound (I-S), having an XRPD pattern comprising peaks at approximately 17.00, 19.73, and
25.86 degrees 2?;

comprises a hemi D-tartrate salt of Compound (I-S), having an XRPD pattern comprising peaks at approximately 6.21, 12.91,
and 16.32 degrees 2?;

comprises a L-tartrate salt of Compound (I-S), having an XRPD pattern comprising peaks at approximately 6.27, 10.90, and 15.32
degrees 2?;

comprises a tosylate salt of Compound (I-S), having an XRPD pattern comprising peaks at approximately 9.77, 15.41, and 19.25
degrees 2?; or

comprises a (+) camphorsulfonic acid salt of Compound (I-S), having an XRPD pattern comprising peaks at approximately 9.05,
14.61, and 16.82 degrees 2?;

wherein the cancer, immune-related disease or disorder, or inflammatory disease or disorder is lupus, scleroderma, Sjögren
syndrome, ANCA-induced vasculitis, anti-phospholipid syndrome, myasthenia gravis, systemic lupus erythematosus (SLE), cutaneous
lupus erythematosus (CLE), discoid lupus erythematosus (DLE), drug-induced lupus, or multiple myeloma.

US Pat. No. 9,822,094

ARYLMETHOXY ISOINDOLINE DERIVATIVES AND COMPOSITIONS COMPRISING AND METHODS OF USING THE SAME

Celgene Corporation, Sum...

1. A compound of formula (IV):
or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein:
X is NR11 or NR12 when only one of R11 and R12 is attached to X, or X is CR11R12 when both R11 and R12 are attached to X;

Y is CH2 or C?O;

R11 and R12 are each independently hydrogen, —(C1-C6)alkyl, —(C1-C6)alkyl-(C3-C6)cycloalkyl, —(C1-C6)alkoxy, —(C6-C10)aryl, —CO(C1-C6)alkyl, —CO(C3-C6)cycloalkyl, —CO(C6-C10)aryl, —COO(C1-C6)alkyl, halogen, hydroxyl, oxo, 3 to 10 membered heterocycle, 6 to 10 membered heteroaryl, —NHCO(C1-C6)alkyl, —(CH2)n-phenyl, —SO2(C1-C6)alkyl, —SO2(C3-C6)cycloalkyl, —SO2(C6-C10)aryl or —NR14R15, wherein the alkyl, aryl or heteroaryl portion of each of the groups may be optionally substituted with one or more halogen,
hydroxyl or —(C1-C6)alkoxy;

R13 is hydrogen or —(C1-C6)alkyl;

R14 and R15 are each independently hydrogen or —(C1-C6)alkyl; and

n is 0, 1, 2 or 3.
US Pat. No. 9,993,467

FORMULATIONS OF 4-AMINO-2-(2,6-DIOXOPIPERIDINE-3-YL)ISOINDOLINE-1,3-DIONE

Celgene Corporation, Sum...

1. An oral dosage form in the form of a capsule which comprises: 1) pomalidomide at an amount of 0.1 to 3 weight percent of the total weight of the composition; 2) a binder or filler at an amount of 90 to 99 weight percent of total weight of the composition, wherein the binder or filler is a mixture of starch and mannitol; andwherein the ratio of mannitol:starch in the dosage form is from about 1:1 to about 1:1.5.

US Pat. No. 9,884,042

FORMULATIONS OF CYCLOPROPANECARBOXYLIC ACID {2-[(1S)-1-(3-ETHOXY-4-METHOXY-PHENYL)-2-METHANESULFONYL-ETHYL]-3-OXO-2,3-DIHYDRO-1H-ISOINDOL-4-YL}-AMIDE

Celgene Corporation, Sum...

1. An oral dosage form comprising: 1) an amorphous solid dispersion of a compound of formula (I):
or a pharmaceutically acceptable salt thereof, in a hydrophilic polymer; and 2) a pharmaceutically acceptable carrier or excipient;
and
wherein the dosage form comprises from about 5% to about 10% by weight of the compound of formula (I);
wherein the dispersion consists of from about 15% to about 25% by weight of the compound of formula (I) and from about 75%
to about 85% by weight of hydrophilic polymer;

wherein the dosage form comprises from about 33% to about 67% percent by weight of the amorphous solid dispersion; and
wherein the dosage form comprises 24% by weight of microcrystalline cellulose; wherein maximum-compactibility grade microcrystalline
cellulose is present at an amount of 10% by weight of the total dosage form and the remaining portion of the microcrystalline
cellulose is of a lower compactibility grade than the maximum-compactibility grade.

US Pat. No. 9,872,854

METHODS FOR THE TREATMENT OF PSORIATIC ARTHRITIS USING APREMILAST

Celgene Corporation, Sum...

1. A method of treating psoriatic arthritis, which comprises orally administering to a patient having psoriatic arthritis
escalating doses of stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione,
or a pharmaceutically acceptable polymorph, salt or solvate thereof, wherein the method consists of the following dosing schedule:
(i) 10 mg in the morning on the first day of administration;
(ii) 10 mg in the morning and 10 mg after noon on the second day of administration;
(iii) 10 mg in the morning and 20 mg after noon on the third day of administration;
(iv) 20 mg in the morning and 20 mg after noon on the fourth day of administration;
(v) 20 mg in the morning and 30 mg after noon on the fifth day of administration; and
(vi) 30 mg in the morning and 30 mg after noon on the sixth and every subsequent day of administration.
US Pat. No. 10,047,151

METHODS FOR THE TREATMENT OF CANCER AND INFLAMMATORY DISEASES USING CEREBLON AS A PREDICTOR

CELGENE CORPORATION, Sum...

1. An isolated antibody or antigen binding fragment thereof that immunospecifically binds to an epitope in CRBN, wherein the epitope has the amino acid sequence SEQ ID NO:1, and wherein the isolated antibody comprises(i) a heavy chain having complementarity determining regions (CDRs) consisting of the amino acids of the CDRs of SEQ ID NO: 5 and a light chain having complementarity determining regions (CDRs) consisting of the amino acids of the CDRs of SEQ ID NO: 7; or
(ii) a heavy chain having complementarity determining regions (CDRs) consisting of the amino acids of the CDRs of SEQ ID NO: 9 and a light chain having complementarity determining regions (CDRs) consisting of the amino acids of the CDRs of SEQ ID NO: 11.

US Pat. No. 9,968,596

ANTIPROLIFERATIVE COMPOUNDS AND METHODS OF USE THEREOF

Celgene Corporation, Sum...

1. A method of synthesizing a compound of Formula I:or an enantiomer or a mixture of enantiomers thereof, or a pharmaceutically acceptable salt, solvate or hydrate thereof, comprising contacting
wherein R1 is optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl or optionally substituted heterocyclyl;
R2 and R3 are each halo;
where the substituents on R1, when present, are one to three Q groups, where each Q is independently alkyl, halo, haloalkyl, alkoxyalkyl, oxo, hydroxyl, alkoxy, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted aryl, optionally substituted heteroaryl, —R4OR5, —R4OR5—R4OR5, —R4N(R6)(R7), —R4SR5, —R4OR4N(R6)(R7), —R4OR4C(J)N(R6)(R7), —C(J)R9 or R4S(O)tR8;
each R4 is independently alkylene, alkenylene or a direct bond;
each R5 is independently hydrogen, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, aryl, heteroaryl, heterocyclyl or heterocyclylalkyl, where alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, aryl, heteroaryl, heterocyclyl or heterocyclylalkyl groups in R5 are each independently optionally substituted with 1-3 Q1 groups, where each Q1 is independently alkyl, haloalkyl or halo;
R6 and R7 are selected as follows:
i) R6 and R7 are each independently hydrogen or alkyl; or
ii) R6 and R7 together with the nitrogen atom on which they are substituted form a 5 or 6-membered heterocyclyl or heteroaryl ring, optionally substituted with one or two halo, alkyl or haloalkyl;
R8 is alkyl, haloalkyl, or hydroxyalkyl;
R9 is alkyl or aryl;
J is O or S; and
t is 1 or 2.
US Pat. No. 9,839,632

METHODS AND COMPOSITIONS USING 4-AMINO-2-(2,6-DIOXO-PIPERIDINE-3-YL)-ISOINDOLINE-1,3-DIONE FOR TREATMENT AND MANAGEMENT OF CENTRAL NERVOUS SYSTEM CANCERS

Celgene Corporation, Sum...

1. A method of increasing macrophages or natural killer cells in tumor microenvironment in a human having a central nervous
system cancer, which comprises administering to a human in need thereof a therapeutically effective amount of 4-amino-2-(2,6-dioxo-piperidine-3-yl)-isoindoline-1,3-dione.
US Pat. No. 10,093,647

CRYSTALLINE 4-AMINO-2-(2,6-DIOXOPIPERIDINE-3-YL)ISOINDOLINE-1,3-DIONE DIHYDRATE, COMPOSITIONS AND METHODS OF USE THEREOF

Celgene Corporation, Sum...

1. Crystalline 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione dihydrate, having an X-ray powder diffraction pattern comprising peaks at 13.9, 16.6, and 25.5 degrees 2?±0.2 degrees 2?.
US Pat. No. 10,093,649

CRYSTALLINE 4-AMINO-2-(2,6-DIOXOPIPERIDINE-3-YL)ISOINDOLINE-1,3-DIONE MONOHYDRATE, COMPOSITIONS AND METHODS OF USE THEREOF

Celgene Corporation, Sum...

1. Crystalline 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione monohydrate, having an X-ray powder diffraction pattern comprising peaks at 11.8, 17.1, and 24.2 degrees 2?±0.2 degrees 2?.
US Pat. No. 9,968,627

SOLID FORMS COMPRISING 4-AMINO-1-?-D-RIBOFURANOSYL-1,3,5-TRIAZIN-2(1H)-ONE AND A COFORMER, COMPOSITIONS AND METHODS OF USE THEREOF

Celgene Corporation, Sum...

1. A solid form comprising (a) 4-amino-1-?-D-ribofuranosyl-1,3,5-triazin-2(1H)-one, or a pharmaceutically acceptable salt, solvate, hydrate, stereoisomer, prodrug, or clathrate thereof; and (b) a conformer selected from the group consisting of glycine, propyl gallate, and nicotinamide.

US Pat. No. 9,920,027

4?-O-SUBSTITUTED ISOINDOLINE DERIVATIVES AND COMPOSITIONS COMPRISING AND METHODS OF USING THE SAME

Celgene Corporation, Sum...

1. A compound of formula:

or a pharmaceutically acceptable salt, solvate, prodrug, clathrate, or stereoisomer thereof, wherein:
Y is C?O or CH2; and

R1 is alkenyl, alkynyl, bicyclic aryl, cycloalkyl, cycloalkylalkyl, arylaminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl,
alkoxycarbonyl, or cycloalkylcarbonyl; and wherein R1 is optionally substituted with one or more groups selected from alkoxy, halo, alkyl, carboxy, alkylaminocarbonyl, alkoxycarbonyl,
nitro, amine, nitrile, haloalkyl, hydroxy, and alkyl sulfonyl.

US Pat. No. 9,828,361

ARYLMETHOXY ISOINDOLINE DERIVATIVES AND COMPOSITIONS COMPRISING AND METHODS OF USING THE SAME

Celgene Corporation, Sum...

1. A compound of the formula:
or a pharmaceutically acceptable salt or stereoisomer thereof.

US Pat. No. 10,064,863

FORMULATIONS OF 3-(5-AMINO-2-METHYL-4-OXO-4H-QUINAZOLIN-3-YL)-PIPERIDINE-2,6-DIONE

Celgene Corporation, Sum...

1. An oral dosage form in the form of a capsule, said dosage form comprising a composition, wherein the composition comprises: Compound A (3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione), or an enantiomer or a mixture of enantiomers thereof, a pharmaceutically acceptable salt, solvate, hydrate, co-crystal, clathrate, or polymorph thereof, at an amount of about 0.5 to about 5 weight percent of the total weight of the composition; a binder or filler selected from microcrystalline cellulose, starch, and mannitol at an amount of about 90 to 98 weight percent of total weight of the composition, stearic acid in an amount of about 0 to 2 weight percent of total weight of the composition, and a disintegrant selected from crospovidone Type A and colloidal silicon dioxide at an amount of about 1 to 5 weight percent of total weight of the composition.

US Pat. No. 10,016,436

ANIMAL AND HUMAN ANTI-MALARIAL AGENTS

Celgene Corporation, Sum...

1. A Purine Compound of formula (I),
or a pharmaceutically acceptable salt, tautomer, isotopologue, or stereoisomer thereof, wherein
R1 is CR1aR1bR1c, wherein R1a and R1b are (C1-4)alkyl and R1c is H or (C1-4)alkyl; or R1a and R1b form a 3-6 membered cycloalkyl or 3-6 membered heterocyclyl, and R1c is H or (C1-4)alkyl;
R2 is L-R2a or L-R2b,
L is a bond or (C1-2 alkyl);
R2a is 3-6 membered N-containing heterocyclyl or heteroaryl, each optionally substituted with one or more (C1-4)alkyl, or (C1-4)alkyl-NR2,
R2b is (C1-4 branched or unbranched alkyl)-NR2,
R3 is phenyl or pyridyl, substituted with at least one halogen, CN, (C1-4)alkyl, or O(C1-4)alkyl, wherein the alkyl is optionally fluorinated; and
R is H or (C1-4) alkyl;
provided the Purine Compound is not
4-(2-(isopropylamino)-8-((2,4,6-trifluorophenyl)amino)-9H-purin-9-yl)pyrrolidin-2-one;
N2-cyclopentyl-N8-(2-fluorophenyl)-9-(piperidin-4-yl)-9H-purine-2,8-diamine; or
N2-cyclohexyl-N8-(2-fluorophenyl)-9-(piperidin-4-ylmethyl)-9H-purine-2,8-diamine.

US Pat. No. 10,001,483

METHODS FOR THE TREATMENT OF KAPOSI'S SARCOMA OR KSHV-INDUCED LYMPHOMA USING IMMUNOMODULATORY COMPOUNDS, AND USES OF BIOMARKERS

Celgene Corporation, Sum...

1. A method of treating or managing Kaposi's sarcoma-associated herpesvirus (KSHV) induced lymphoma, comprising:identifying a patient having KSHV-induced lymphoma sensitive to treatment with a compound of the formula:

or a pharmaceutically acceptable salt, solvate or stereoisomer thereof;
wherein said identifying comprises measuring a level of major histocompatibility complex class I (MHC-1) in a biological sample obtained from the patient, wherein a decreased level of MHC-1 relative to a control sample indicates a likelihood that the patient is sensitive to treatment with the compound; and
(ii) administering to the patient a therapeutically effective amount of the compound in a 28 day cycle comprising 21 consecutive days of administration followed by seven consecutive days of rest.

US Pat. No. 9,938,254

ANTIPROLIFERATIVE COMPOUNDS, AND THEIR PHARMACEUTICAL COMPOSITIONS AND USES

Celgene Corporation, Sum...

8. A compound of Formula B-I:or a stereoisomer or mixture of stereoisomers, tautomer, pharmaceutically acceptable salt, solvate, hydrate, co-crystal, clathrate, isotopologue or polymorph thereof, wherein:each R? is independently H or optionally substituted alkyl; or optionally substituted cycloalkyl;
R? is H or optionally substituted alkyl;
R1 is optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl or optionally substituted heterocyclyl;
R2 and R3 are each halo;
where the substituents on R1, when present are one to three groups Q, where each Q is independently alkyl, halo, haloalkyl, hydroxyl, alkoxy, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, —R4OR5, —R4SR5, —R4N(R6)(R7), R4OR4N(R6)(R7) or R4OR4C(J)N(R6)(R7);
J is O or S;
each R4 is independently alkylene, alkenylene or a direct bond;
each R5 is independently hydrogen, alkyl, haloalkyl or hydroxyalkyl; and
R6 and R7 are each independently hydrogen or alkyl or R6 and R7 together with the nitrogen atom on which they are substituted form a 5 or 6-membered heterocyclyl or heteroaryl ring, optionally substituted with one or two halo, alkyl or haloalkyl.

US Pat. No. 9,822,093

PROCESSES FOR THE PREPARATION OF 4-AMINO-2-(2,6-DIOXOPIPERIDIN-3-YL)ISOINDOLINE-1,3-DIONE COMPOUNDS

Celgene Corporation, Sum...

1. A process for preparing a compound of Formula (I):

or a pharmaceutically acceptable free amine, salt, or stereoisomer thereof, comprising the step of cyclizing a compound of
Formula (II) or (IIA):


or a salt thereof with a cyclizing agent of Formula (V):

wherein R1 is H, F, benzyl, (C1-C8)alkyl, (C2-C8)alkenyl, or (C2-C8)alkynyl; and each of X and Y is independently an unsubstituted or substituted imidazolyl, benzimidazolyl or benzotriazolyl;

wherein, the compound of Formula (II) or (IIA) is prepared by reducing a compound of Formula (III) or (IIIA) respectively:

with a reducing agent, wherein R1 is H, F, benzyl, (C1-C8)alkyl, (C2-C8)alkenyl, or (C2-C8)alkynyl;

wherein the compound of Formula (III) or (IIIA) is prepared by reacting 3-nitrophthalic anhydride with a compound of Formula
(IV) or (IVA) respectively:


wherein R1 is H, F, benzyl, (C1-C8)alkyl, (C2-C8)alkenyl, or (C2-C8)alkynyl.

US Pat. No. 10,034,872

METHODS OF TREATING MULTIPLE MYELOMA WITH IMMUNOMODULATORY COMPOUNDS IN COMBINATION WITH ANTIBODIES

Celgene Corporation, Sum...

1. A method of treating multiple myeloma in a patient having multiple myeloma and having received stem cell transplantation, which comprises:a. determining the minimal residual disease (MRD) status of the patient following the stem cell transplantation, wherein the patient has received induction therapy with a compound having the formula:

or a pharmaceutically acceptable salt, solvate or stereoisomer thereof before receiving the stem cell transplantation; and
b. wherein if the patient is MRD positive, administering to the patient about 1 to about 50 mg per day of the compound
or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, in combination with a therapeutically effective amount of an anti-CS1 antibody.
US Pat. No. 9,975,872

PROCESSES FOR THE PREPARATION OF (S)-3-(4-((4-(MORPHOLINOMETHYL)BENZYL)OXY)-1-OXOISOINDOLIN-2-YL)PIPERIDINE-2,6-DIONE AND PHARMACEUTICALLY ACCEPTABLE FORMS THEREOF

Celgene Corporation, Sum...

1. A process to increase the enantiopurity of (S)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione hydrochloride or a solvate thereof, comprising recrystallization or trituration of a first sample of (S)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione hydrochloride or a solvate thereof in methanol, resulting in a second sample of (S)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione hydrochloride or a solvate thereof, wherein the second sample has a higher enantiomeric excess (ee) than the first sample.

US Pat. No. 9,974,780

SOLID FORMS COMPRISING 4-AMINO-2-(2,6-DIOXOPIPERIDINE-3-YL)ISOINDOLINE-1,3-DIONE AND A COFORMER, COMPOSITIONS AND METHODS OF USE THEREOF

Celgene Corporation, Sum...

1. A method of treating multiple myeloma, the method comprising administering to a patient a solid form comprising (a) 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione (pomalidomide); and (b) a coformer; whereinthe coformer is gallic acid and the solid form has an X-ray powder diffraction (XRPD) pattern comprising peaks at 22.98, 26.16, and 26.90 degrees 2?±0.2 degrees 2?;
the coformer is vanillin and the solid form has an XRPD pattern comprising peaks at 13.09, 17.30, and 25.61 degrees 2?±0.2 degrees 2?;
the coformer is cyclamic acid and the solid form has an XRPD pattern comprising peaks at 6.42, 7.88, and 15.73 degrees 2?±0.2 degrees 2?;
the coformer is D-glucose and the solid form has an XRPD pattern comprising peaks at 17.09, 20.68, and 25.52 degrees 2?±0.2 degrees 2?;
the coformer is propyl gallate and the solid form has an XRPD pattern comprising peaks at 7.78, 25.23, and 25.61 degrees 2?±0.2 degrees 2?;
the coformer is saccharin and the solid form has an XRPD pattern comprising peaks at 15.98, 19.09, and 25.10 degrees 2?±0.2 degrees 2?;
the coformer is sodium lauryl sulfate and the solid form has an XRPD pattern comprising peaks at 2.66, 5.30, and 7.93 degrees 2?±0.2 degrees 2?;
the coformer is magnesium bromide and the solid form has an XRPD pattern comprising peaks at 3.23, 28.76, and 29.95 degrees 2?±0.2 degrees 2?;
the coformer is malonic acid and the solid form has an XRPD pattern comprising peaks at 12.23, 16.63, and 25.58 degrees 2?±0.2 degrees 2?;
the coformer is maltol and the solid form has an XRPD pattern comprising peaks at 16.51, 17.09, and 25.73 degrees 2?±0.2 degrees 2?;
the coformer is methyl paraben and the solid form has an XRPD pattern comprising peaks at 18.73, 25.69, and 26.70 degrees 2?±0.2 degrees 2?; or
the coformer is zinc chloride and the solid form has an XRPD pattern comprising peaks at 2.38, 17.17, and 25.71 degrees 2?±0.2 degrees 2?.

US Pat. No. 9,969,712

PROCESS FOR THE PREPARATION OF ISOTOPOLOGUES OF 3-(4-((4-(MORPHOLINOMETHYL)BENZYL)OXY)-1-OXOISOINDOLIN-2-YL)PIPERIDINE-2,6-DIONE AND PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF

Celgene Corporation, Sum...

1. A method of treating or managing a disease or disorder, comprising administering to a subject in need of such treatment or management a therapeutically effective amount of a compound of the formula:
or a pharmaceutically acceptable salt or solvate thereof, wherein:
at least one of Y1, Y2, Y3, Y4, Y5, Y6, Y7, Y8, Y9, Y1, Y11, Y12, Y13 Y14, Y15, Y16, Y17, Y18, Y19, Y20, Y21, Y22, Y23, Y24, Y25, Y26, and Y27 is a hydrogen that is isotopically enriched with deuterium, and the others of Y1, Y3, Y4, Y5, Y6, Y7, Y8, Y9, Y11, Y12, Y13 Y14, Y15, Y16, Y17, Y18, Y19, Y20, Y21, Y22, Y23, Y24, Y25, Y26, and Y27 are non-enriched hydrogen atoms, and
wherein the disease or disorder is an inflammatory or immune-related disease or disorder, or a cancer,
provided that the compound is not

US Pat. No. 9,925,207

METHODS OF TREATING MYELODYSPLASTIC SYNDROMES USING LENALIDOMIDE

Celgene Corporation, Sum...

1. A method of treating acute myeloid leukemia (AML) associated with a myelodysplastic syndrome, the method comprising administering to a patient having AML a therapeutically effective amount of 5-azacytidine, and a therapeutically effective amount of 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione or a pharmaceutically acceptable salt thereof wherein 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione is administered in an amount of about 5 mg to about 25 mg per day.
US Pat. No. 10,093,648

CRYSTALLINE 4-AMINO-2-(2,6-DIOXOPIPERIDINE-3-YL)ISOINDOLINE-1,3-DIONE HEMIHYDRATE, COMPOSITIONS AND METHODS OF USE THEREOF

Celgene Corporation, Sum...

1. Crystalline 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione hemihydrate, having an X-ray powder diffraction pattern comprising peaks at 12.0, 17.2, and 25.6 degrees 2?±0.2 degrees 2?.

US Pat. No. 10,010,555

ANIMAL AND HUMAN ANTI-TRYPANOSOMONAL AND ANTI-LEISHMANIA AGENTS

Celgene Corporation, Sum...

1. An Aminopurine Compound of formula (I):
or a pharmaceutically acceptable salt, tautomer, isotopologue, or stereoisomer thereof, wherein:
R1 is CR1aR1bR1c, wherein each of R1a R1b and R1c is independently (C1-4)alkyl, or(C1-4)alkyl(OR); or R1a and R1b and the carbon to which they are attached form a 3-6 membered cycloalkyl or 3-6 membered heterocyclyl, and R1c is (C1-4)alkyl;
R2 is cycloalkyl or aryl, substituted with at least one NR2, OR, CN, NRC(O)R, CH2OR, CH2NR2, CH2NRCOR, CH2NRCOOR?, or heterocyclylalkyl;
R3 is phenyl or pyridyl, optionally substituted with at least one halogen, CN, (C1-2)alkyl, or O(C1-2)alkyl, wherein the alkyl is optionally fluorinated;
R is H or (C1-4) alkyl; and
R? is (C1-4)alkyl;
provided the Aminopurine Compound is not
4-(2-(tert-butylamino)-8-((2,6-difluorophenyl)amino)-9H-purin-9-yl)cyclohexan-1-ol;
4-(2-(tert-butylamino)-8-((2,4,6-trifluorophenyl)amino)-9H-purin-9-yl)cyclohexan-1-ol; or
4-(2-(tert-butylamino)-8-((2,4-difluorophenyl)amino)-9H-purin-9-yl)cyclohexan-1-ol.

US Pat. No. 10,252,981

METHODS OF SYNTHESIS OF (1R,2R,5R)-5-AMINO-2-METHYLCYCLOHEXANOL HYDROCHLORIDE AND INTERMEDIATES USEFUL THEREIN

Celgene Corporation, Sum...

1. A method for preparing a compound of formula (A),
the method comprising the steps of:
(a) contacting a compound of formula (1),

with a compound of formula (2),

in the presence of a Lewis Acid in a solvent to provide a compound of formula (3),

(b) contacting the compound of formula (3) of step (a) with an aqueous base to provide a compound of formula (4),

(c) contacting the compound of formula (4) of step (b) with DMF and a chlorinating agent in an organic solvent, followed by treatment of the resulting acid chloride derivative with aqueous ammonia to provide a compound of formula (5),

(d) contacting the compound of formula (5) of step (c) with an aqueous solution of NaOH and NaOCl to provide a compound of formula (6),

(e) contacting the compound of formula (6) of step (d) with (+)-dibenzoyl-D-tartaric acid monohydrate in a solvent to provide a compound of formula (7),

(f) contacting the compound of formula (7) of step (e) with an aqueous base, followed by treatment of the resulting free base with Boc2O in an organic solvent to provide a compound of formula (8),

(g) contacting the compound of formula (8) of step (f) with a mixture of a reducing agent, a chiral auxiliary and a Lewis acid in a solvent, followed by treatment with an oxidant in the presence of a base to provide a compound of formula (9),
and(h) contacting the compound of formula (9) of step (g) with a solution of hydrochloric acid in a solvent to provide the compound of formula (A).

US Pat. No. 10,137,130

METHODS OF TREATMENT OF MALIGNANCIES

Celgene Corporation, Sum...

1. A method of treating acute myeloid leukemia in a subject comprising administering to the subject a mutant isocitrate dehydrogenase 2 (IDH2) inhibitor 2-methyl-1-[(4-[6-(trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl]amino}-1,3,5-triazin-2-yl)amino]propan-2-ol having the following formula:or a pharmaceutically acceptable salt, solvate, or tautomer thereof, wherein the acute myeloid leukemia is characterized by the presence of a mutant allele of IDH2 and the absence of a mutant allele of FLT3.

US Pat. No. 10,080,801

FORMULATIONS OF (S)-3-(4-((4-(MORPHOLINOMETHYL)BENZYL)OXY)-1-OXOISOINDOLIN-2-YL)PIPERIDINE-2,6-DIONE

Celgene Corporation, Sum...

1. An oral dosage form in the form of a capsule which comprises: 1) Compound A of the following structure:
or a pharmaceutically acceptable prodrug, salt, solvate, hydrate, clathrate, stereoisomer, tautomer, or racemic mixtures thereof, at an amount of about 0.1 to about 3 weight percent of the total weight of the dosage form; 2) a carrier or excipient at an amount of about 90 to 99.9 weight percent of total weight of the oral dosage form, wherein the carrier or excipient is a mixture of starch and lactose; and 3) a lubricant at an amount of 0.01 to 1 weight percent of total weight of the oral dosage form, wherein the lubricant is stearic acid.
US Pat. No. 10,227,325

ANTIPROLIFERATIVE COMPOUNDS, AND THEIR PHARMACEUTICAL COMPOSITIONS AND USES

Celgene Corporation, Sum...

1. A compound, wherein the compound is:(3-(5-((2,2-difluoro-2-(4-fluorophenyl)acetamido)methyl)-1-oxoisoindolin-2-yl)-2,6-dioxopiperidin-1-yl)methyl dihydrogen phosphate,
(3-(5-((2-(4-chlorophenyl)-2,2-difluoroacetamido)methyl)-1-oxoisoindolin-2-yl)-2,6-dioxopiperidin-1-yl)methyl dihydrogen phosphate,
(3-(5-((2,2-difluoro-2-(4-fluorophenyl)acetamido)methyl)-1-oxoisoindolin-2-yl)-2,6-dioxopiperidin-1-yl)methyl L-valinate,
(3-(5-((2-(4-chlorophenyl)-2,2-difluoroacetamido)methyl)-1-oxoisoindolin-2-yl)-2,6-dioxopiperidin-1-yl)methyl L-valinate,
or a stereoisomer or mixture of stereoisomers, tautomer, pharmaceutically acceptable salt, solvate, hydrate, co-crystal, clathrate, isotopologue or polymorph thereof.
US Pat. No. 10,150,816

CHIMERIC ANTIGEN RECEPTORS

CELGENE CORPORATION, Sum...

1. A polypeptide comprising (i) a transmembrane domain from PD-1, (ii) a CD3? intracellular signaling domain, and (iii) an extracellular domain that binds to an antigen on a tumor cell, wherein said extracellular domain is an antibody or an antigen-binding portion thereof, and wherein the intracellular domain and the extracellular domain of said polypeptide are not from PD-1, wherein said polypeptide, when expressed on the surface of a T lymphocyte, directs the T lymphocyte to kill a cell expressing said antigen.

US Pat. No. 10,328,077

TREATMENT OF RELAPSED AND/OR REFRACTORY SOLID TUMORS AND NON-HODGKIN'S LYMPHOMAS

Celgene Corporation, Sum...

1. A method for the treatment of human merkel cell carcinoma, gastric neuroendocrine carcinoma, or small cell lung cancer comprising the administration to a patient in need thereof an effective amount of a compound having the structure of Formula (I), or a pharmaceutically acceptable salt thereof,
wherein,
W is N, C—H, or C—F;
X is hydrogen, halogen, —CN, optionally substituted alkyl, optionally substituted alkynyl, optionally substituted carbocyclylalkynyl, optionally substituted aryl, or optionally substituted heteroaryl;
Y is hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, or optionally substituted cycloalkylalkyl;
Z is an optionally substituted group chosen from alkyl, carbocyclyl, C-attached heterocyclyl, N-attached heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, —O-heterocyclyl, —N(R)-heterocyclyl, —O-heterocyclylalkyl, —N(R)-heterocyclylalkyl, —N(R)(C1-C4alkylene)-NR2, —O(C1-C4alkylene)-NR2; and
R is hydrogen or C1-C4alkyl.

US Pat. No. 10,245,258

TREATMENT OF A HEMATOLOGIC MALIGNANCY WITH 2-(4-CHLOROPHENYL)-N-((2-(2,6-DIOXOPIPERIDIN-3-YL)-1-OXOISOINDOLIN-5-YL)METHYL)-2,2-DIFLUOROACETAMIDE

Celgene Corporation, Sum...

1. A method for treating, managing, or ameliorating a hematological cancer comprising administering to a subject in need thereof 2-(4-chlorophenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2,2-difluoroacetamide, which has the following structure:or a stereoisomer or mixture of stereoisomers, isotopologue, pharmaceutically acceptable salt, tautomer, solvate, hydrate, co-crystal, clathrate, or polymorph thereof (Compound 1), wherein Compound 1 is administered to the subject in a dose of about 0.1 mg to about 20 mg, and the subject is further administered one or more of calcium, calcitriol, or vitamin D supplementation.

US Pat. No. 10,245,266

3-(4-((4-MORPHOLINOMETHYL-BENZYL)OXY)-1-OXOISOINDOLIN-2-YL)PIPERIDINE-2,6-DIONE FOR THE TREATMENT OF SYSTEMIC LUPUS ERYTHEMATOSUS

Celgene Corporation, Sum...

1. A method for identifying a subject having systemic lupus erythematosus (SLE) who is likely to be responsive to a treatment with a compound of formula Ior a pharmaceutically acceptable salt, stereoisomer, tautomer or racemic mixture thereof, comprising:(a) determining the level of a biomarker in a first sample from the subject, wherein the biomarker is selected from the group consisting of CRBN, IKZF1 (Ikaros), and IKZF3 (Aiolos); and
(b) comparing the level of the biomarker in the first sample to a reference level of the biomarker; wherein the subject is likely to be responsive to the treatment if the level of the biomarker in the first sample is higher than the reference level of the biomarker.
US Pat. No. 10,238,690

MODIFIED T LYMPHOCYTES COMPRISING AN INDUCIBLE CASPASE AND METHODS OF APOPTOSIS

CELGENE CORPORATION, Sum...

1. A T lymphocyte comprising an artificial cell death polypeptide comprising an apoptosis-inducing domain, wherein said artificial cell death polypeptide is a transmembrane protein comprising an extracellular domain that comprises a CD20 epitope, a transmembrane domain, and an intracellular domain comprising said apoptosis-inducing domain, wherein said apoptosis-inducing domain is caspase 3, caspase 8 or caspase 9, wherein said polypeptide is dimerizable using an anti-CD20 antibody that binds to said CD20 epitope, and wherein when said antibody dimerizes said polypeptide, an apoptosis-inducing signal is generated in said T lymphocyte.

US Pat. No. 10,206,914

METHODS FOR TREATING MULTIPLE MYELOMA WITH 3-(4-AMINO-1-OXO-1,3-DIHYDROISOINDOL-2-YL)-PIPERIDINE-2,6-DIONE AFTER STEM CELL TRANSPLANTATION

Celgene Corporation, Sum...

1. A method of treating multiple myeloma, the method comprising administering to a patient having multiple myeloma about 1 to about 50 mg per day of a compound having the formula:or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein the patient has previously received hematopoietic stem cell transplantation.
US Pat. No. 10,195,249

ACTIVIN-ACTRII ANTAGONISTS AND USES FOR TREATING BONE AND OTHER DISORDERS

Celgene Corporation, Sum...

1. A method for treating vascular calcification in a subject in need thereof, wherein the method comprises administering a therapeutically effective amount of an ActRIIA inhibitor to the subject, wherein the ActRIIA inhibitor is a polypeptide comprising an amino acid sequence selected from the group consisting of:a. 90% identical to SEQ ID NO:2;
b. 95% identical to SEQ ID NO:2;
c. 98% identical to SEQ ID NO:2;
d. SEQ ID NO:2;
e. 90% identical to SEQ ID NO:3;
f. 95% identical to SEQ ID NO:3;
g. 98% identical to SEQ ID NO:3;
h. SEQ ID NO:3;
i. 90% identical to SEQ ID NO:6;
j. 95% identical to SEQ ID NO:6;
k. 98% identical to SEQ ID NO:6;
l. SEQ ID NO:6;
m. 90% identical to SEQ ID NO:7;
n. 95% identical to SEQ ID NO:7;
o. 98% identical to SEQ ID NO:7;
p. SEQ ID NO:7;
q. 90% identical to SEQ ID NO:12;
r. 95% identical to SEQ ID NO:12;
s. 98% identical to SEQ ID NO:12; and
t. SEQ ID NO:12.
US Pat. No. 10,189,808

SOLID FORMS OF 2-(4-CHLOROPHENYL)-N-((2-(2,6-DIOXOPIPERIDIN-3-YL)-1-OXOISOINDOLIN-5-YL)METHYL)-2,2-DIFLUOROACETAMIDE, AND THEIR PHARMACEUTICAL COMPOSITIONS AND USES

Celgene Corporation, Sum...

1. A solid form of 2-(4-chlorophenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2,2-difluoroacetamide or a tautomer thereof, which is Form C having an X-ray powder diffraction pattern comprising peaks at about 16.7, 16.9, 17.7 or 24.7 degrees 2?.

US Pat. No. 10,189,814

ARYLMETHOXY ISOINDOLINE DERIVATIVES AND COMPOSITIONS COMPRISING AND METHODS OF USING THE SAME

Celgene Corporation, Sum...

1. A method for treating or managing a disease or disorder for therapeutic benefit comprising administering to a patient a therapeutically effective amount of a compound of formula (IV):
or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein:
X is NR11 or NR12 when only one of R11 and R12 is attached to X, or X is CR11R12 when both R11 and R12 are attached to X;
Y is CH2 or C?O;
R11 and R12 are each independently hydrogen, —(C1-C6)alkyl, —(C1-C6)alkyl-(C3-C6)cycloalkyl, —(C1-C6)alkoxy, —(C6-C10)aryl, —CO(C1-C6)alkyl, —CO(C3-C6)cycloalkyl, —CO(C6-C10)aryl, —COO(C1-C6)alkyl, halogen, hydroxyl, oxo, 3 to 10 membered heterocycle, 6 to 10 membered heteroaryl, —NHCO(C1-C6)alkyl, —(CH2)n-phenyl, —SO2(C1-C6)alkyl, —SO2(C3-C6)cycloalkyl, —SO2(C6-C10)aryl or —NR14R15, wherein the alkyl, aryl or heteroaryl portion of each of the groups may be optionally substituted with one or more halogen, hydroxyl or —(C1-C6)alkoxy;
R13 is hydrogen or —(C1-C6)alkyl;
R14 and R15 are each independently hydrogen or —(C1-C6)alkyl; and
n is 0, 1, 2 or 3; and
wherein the disease or disorder is cancer, a disorder associated with angiogenesis, pain, macular degeneration, a skin disease, a parasitic disease, CNS injury, atherosclerosis, dysfunctional sleep, an infectious disease, or hemoglobinopathy.

US Pat. No. 10,159,675

CYCLING THERAPY USING 3-(5-AMINO-2-METHYL-4-OXO-4H-QUINAZOLIN-3-YL)-PIPERIDINE-2,6-DIONE

Celgene Corporation, Sum...

1. A method for treating, managing, and/or ameliorating lymphoma, while reducing an adverse effect associated with such treating, managing, and/or ameliorating, said method comprising administering to a patient in need thereof an effective amount of compound 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione, which has the following structure:or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, stereoisomer, tautomer or racemic mixture thereof, wherein the compound is administered to said subject in a cycling therapy, said cycling therapy comprising:an administration period of 5 days followed by a rest period of 2 days.
US Pat. No. 10,092,541

METHODS FOR THE TREATMENT OF DISEASES AMELIORATED BY PDE4 INHIBITION USING DOSAGE TITRATION OF APREMILAST

Celgene Corporation, Sum...

1. A method for treating a patient with stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, wherein the patient is suffering from psoriasis, the method consisting of:(a) administering to the patient stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione in an initial titration dosing schedule consisting of
(i) 10 mg in the morning on the first day of administration;
(ii) 10 mg in the morning and 10 mg after noon on the second day of administration;
(iii) 10 mg in the morning and 20 mg after noon on the third day of administration;
(iv) 20 mg in the morning and 20 mg after noon on the fourth day of administration;
(v) 20 mg in the morning and 30 mg after noon on the fifth day of administration; and
(b) on the sixth and every subsequent day, administering to the patient stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione at a dose of between about 40 mg/day and about 100 mg/day.

US Pat. No. 10,092,542

METHODS OF USING (+)-2-[1-(3-ETHOXY-4-METHOXYPHENYL)-2-METHYLSULFONYLETHYL]-4-ACETYLAMINOISOINDOLINE-1,3-DIONE

Celgene Corporation, Sum...

1. A method of treating or managing bone loss, which comprises administering to a patient a therapeutically effective amount of (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-4-acetylaminoisoindolin-1,3-dione:or a pharmaceutically acceptable salt thereof.
US Pat. No. 10,092,555

COMPOSITIONS AND METHODS FOR INDUCING CONFORMATIONAL CHANGES IN CEREBLON AND OTHER E3 UBIQUITIN LIGASES

CELGENE CORPORATION, Sum...

1. A method of identifying a test compound that induces a cereblon protein (CRBN) conformational change or an alteration of properties of a CRBN surface, wherein the method comprises:(a) (i) obtaining a first crystal of CRBN and a reference compound or an apo-CRBN crystal, and (ii) determining the three-dimensional structure of the first crystal by x-ray diffraction to obtain a first set of atomic coordinates;
(b) (i) obtaining a second crystal comprising CRBN and the test compound, and (ii) determining the three-dimensional structure of the second crystal by x-ray diffraction to obtain a second set of atomic coordinates; and
(c) employing on a computer, the structural coordinates from the first set of atomic coordinates and the second set of atomic coordinates and comparing the two sets with one another wherein identification of a test compound that induces a conformational change or alteration of properties of a CRBN surface is made by identifying a shift in the protein backbone or sidechains in the second set of atomic coordinates as compared to the first set atomic coordinates;
wherein the CRBN conformational change or the alteration of properties of the CRBN surface occurs in a CRBN modifying agent (CMA) binding pocket of the CRBN, or within an adjacent region thereof, and
wherein said first and second crystals comprising CRBN form in space group P212121 or /23 and are human or murine CRBN.
US Pat. No. 10,052,315

FORMULATIONS OF 2-(4-CHLOROPHENYL)-N-((2-(2,6-DIOXOPIPERIDIN-3-YL)-1-OXOISOINDOLIN-5-YL)METHYL)-2,2-DIFLUOROACETAMIDE

Celgene Corporation, Sum...

1. A lyophilized formulation comprising: Compound 1 (2-(4-chlorophenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2,2-difluoroacetamide), or a stereisomer or mixture of stereisomers, pharmaceutically acceptable salt, tautomer, prodrug, solvate, hydrate, co-crystal, clathrate, or polymorph thereof, a buffer and a bulking agent.

US Pat. No. 10,434,095

3-(1-OXO-4-((4-((3-OXOMORPHOLINO)METHYL)BENZYL)OXY)ISOINDOLIN-2-YL)PIPERIDINE-2,6-DIONE AND ISOTOPOLOGUES THEREOF

Celgene Corporation, Sum...

1. A compound of Formula (I):
or an isotopologue thereof, or an enantiomer or a mixture of enantiomers thereof, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof.
US Pat. No. 10,428,145

PD-1 BINDING PROTEINS AND METHODS OF USE THEREOF

Celgene Corporation, Sum...

1. An antibody or antigen-binding fragment thereof that binds to PD-1, wherein the antibody or antigen-binding fragment comprises:a light chain variable region (VL) comprising:
a VL complementarity determining region 1 (CDR1) comprising SEQ ID NO:1,
a VL CDR2 comprising SEQ ID NO:2, and
a VL CDR3 comprising SEQ ID NO:3; and
a heavy chain variable region (VH) comprising:
a VH CDR1 comprising SEQ ID NO:4,
a VH CDR2 comprising SEQ ID NO:5, and
a VH CDR3 comprising SEQ ID NO:6.

US Pat. No. 10,420,771

ANIMAL AND HUMAN ANTI-MALARIAL AGENTS

Celgene Corporation, Sum...

1. A method of treating malaria, comprising administering to a subject having malaria an effective amount of a compound of formula (I),
or a pharmaceutically acceptable salt, tautomer, isotopologue, or stereoisomer thereof, wherein
R1 is CR1aR1bR1c, wherein R1a and R1b are (C1-4)alkyl and R1c is H or (C1-4)alkyl; or R1a and R1b form a 3-6 membered cycloalkyl or 3-6 membered heterocyclyl, and R1c is H or (C1-4)alkyl;
R2 is L-R2a or L-R2b,L is a bond or (C1-2 alkyl);R2a is 3-6 membered N-containing heterocyclyl or heteroaryl, each optionally substituted with one or more (C1-4)alkyl, or (C1-4)alkyl-NR2;R2b is (C1-4 branched or unbranched alkyl)-NR2,R3 is phenyl or pyridyl, substituted with at least one halogen, CN, (C1-4)alkyl, or O(C1-4)alkyl, wherein the alkyl is optionally fluorinated; and
R is H or (C1-4) alkyl.

US Pat. No. 10,420,772

ANIMAL AND HUMAN ANTI-TRYPANOSOMONAL AND ANTI-LEISHMANIA AGENTS

Celgene Corporation, Sum...

1. A method for the treatment of trypanosomosis, trypanosomiasis, or leishmaniasis, the method comprising administering to a subject having trypanosomosis, trypanosomiasis, or leishmaniasis an effective amount of a compound of formula (I):
or a pharmaceutically acceptable salt, tautomer, isotopologue, or stereoisomer thereof, wherein:
R1 is CR1aR1bR1c, wherein each of R1a, R1b and R1c is independently (C1-4)alkyl, or (C1-4)alkyl(OR); or R1a and R1b and the carbon to which they are attached form a 3-6 membered cycloalkyl or 3-6 membered heterocyclyl, and R1c is (C1-4)alkyl;
R2 is cycloalkyl or aryl, substituted with at least one NR2, OR, CN, NRC(O)R, CH2OR, CH2NR2, CH2NRCOR, CH2NRCOOR?, or heterocyclylalkyl;
R3 is phenyl or pyridyl, optionally substituted with at least one halogen, CN, (C1-2)alkyl, or O(C1-2)alkyl, wherein the alkyl is optionally fluorinated;
R is H or (C1-4) alkyl; and
R? is (C1-4)alkyl.
US Pat. No. 10,376,503

SOLID FORMS COMPRISING 4-AMINO-2-(2,6-DIOXOPIPERIDINE-3-YL)ISOINDOLINE-1,3-DIONE AND A COFORMER, COMPOSITIONS AND METHODS OF USE THEREOF

Celgene Corporation, Sum...

1. A method of treating multiple myeloma, the method comprising administering to a patient dexamethasone in combination with a solid form comprising (a) 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione (pomalidomide); and (b) a coformer; whereinthe coformer is gallic acid and the solid form has an X-ray powder diffraction (XRPD) pattern comprising peaks at 22.98, 26.16, and 26.90 degrees 2?±0.2 degrees 2?;
the coformer is vanillin and the solid form has an XRPD pattern comprising peaks at 13.09, 17.30, and 25.61 degrees 2?±0.2 degrees 2?;
the coformer is cyclamic acid and the solid form has an XRPD pattern comprising peaks at 6.42, 7.88, and 15.73 degrees 2?±0.2 degrees 2?;
the coformer is D-glucose and the solid form has an XRPD pattern comprising peaks at 17.09, 20.68, and 25.52 degrees 2?±0.2 degrees 2?;
the coformer is propyl gallate and the solid form has an XRPD pattern comprising peaks at 7.78, 25.23, and 25.61 degrees 2?±0.2 degrees 2?;
the coformer is saccharin and the solid form has an XRPD pattern comprising peaks at 15.98, 19.09, and 25.10 degrees 2?±0.2 degrees 2?;
the coformer is sodium lauryl sulfate and the solid form has an XRPD pattern comprising peaks at 2.66, 5.30, and 7.93 degrees 2?±0.2 degrees 2?;
the coformer is magnesium bromide and the solid form has an XRPD pattern comprising peaks at 3.23, 28.76, and 29.95 degrees 2?±0.2 degrees 2?;
the coformer is malonic acid and the solid form has an XRPD pattern comprising peaks at 12.23, 16.63, and 25.58 degrees 2?±0.2 degrees 2?;
the coformer is maltol and the solid form has an XRPD pattern comprising peaks at 16.51, 17.09, and 25.73 degrees 2?±0.2 degrees 2?;
the coformer is methyl paraben and the solid form has an XRPD pattern comprising peaks at 18.73, 25.69, and 26.70 degrees 2?±0.2 degrees 2?; or
the coformer is zinc chloride and the solid form has an XRPD pattern comprising peaks at 2.38, 17.17, and 25.71 degrees 2?±0.2 degrees 2?.

US Pat. No. 10,335,495

BIOMOLECULE CONJUGATES

CELGENE CORPORATION, Sum...

1. A compound of Formula I
wherein
A is dibenzocyclooctynyl, cyclooct-4-ynoxyl, or (1R,8S,9S)-bicyclo[6.1.0]non-4-yn-9-ylmethyloxy;
D is a maytansinoid;
m is 1;
E is

wherein:
J is an amino acid or peptide;
h is an integer from 0 to 30;
d, e, g, j, and k are each independently an integer from 1 to 30;
each R4 is independently H, alkyl, —N(R3)2, —SR3, and C1-C8 alkoxy, aryl;
each of R3 or R3? is H, C1-C8 alkyl; and
“d is 5” and “R3? is H” are not satisfied simultaneously.
US Pat. No. 10,338,077

METHODS FOR DETERMINING DRUG EFFICACY FOR TREATMENT OF CANCER RATION OF CEREBLON ASSOCIATED PROTEINS

CELGENE CORPORATION, Sum...

1. A method of treating a cancer with lenalidomide in a subject, comprising:(a) obtaining a sample from the subject;
(b) measuring mRNA level of cereblon (CRBN);
(c) measuring mRNA level of IKZF1;
(d) determining the ratio of the mRNA level of CRBN to the mRNA level of IKZF1; and
(e) diagnosing the subject as being likely to be responsive to lenalidomide if the ratio of the mRNA level of CRBN to the mRNA level of IKZF1 is higher than 3;
(f) administering lenalidomide to the subject diagnosed as being likely to be responsive to lenalidomide,
wherein the cancer is an Adult T-cell Leukemia (ATL).
US Pat. No. 10,300,042

APREMILAST FOR THE TREATMENT OF A LIVER DISEASE OR A LIVER FUNCTION ABNORMALITY

Celgene Corporation, Sum...

1. A method of treating or managing a patient having fatty liver disease; hepatic fibrosis; hemochromatosis; acute porphyria; sclerosis cholangitis; cholestatic jaundice; primary biliary cirrhosis; Wilson's disease; or hepatic steatosis, wherein the method comprises orally administering to the patient an effective amount of stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, or a pharmaceutically acceptable prodrug or salt thereof.

US Pat. No. 10,463,672

SALTS AND SOLID FORMS OF (S)-3-(4-((4-(MORPHOLINOMETHYL)BENZYL)OXY)-1-OXOISOINDOLIN-2-YL)PIPERIDINE-2,6-DIONE AND COMPOSITIONS COMPRISING AND METHODS OF USING THE SAME

Celgene Corporation, Sum...

1. A method of treating cancer, an immune-related disease or disorder, an inflammatory disease or disorder, or a symptom thereof in a subject, comprising administering to the subject a therapeutically effective amount of a solid form comprising a racemic Compound (I):or a hydrate or anhydrate thereof, wherein the solid form is crystalline, wherein the solid formcomprises racemic Compound (I), having an XRPD pattern comprising peaks at approximately 4.95, 8.96, and 14.83 degrees 2?; or
comprises racemic Compound (I) and water, having an XRPD pattern comprising peaks at approximately 14.01, 17.28, and 26.21 degrees 2?;
wherein the cancer, immune-related disease or disorder, or inflammatory disease or disorder is lupus, scleroderma, Sjögren syndrome, ANCA-induced vasculitis, anti-phospholipid syndrome, myasthenia gravis, systemic lupus erythematosus (SLE), cutaneous lupus erythematosus (CLE), discoid lupus erythematosus (DLE), drug-induced lupus, or multiple myeloma.

US Pat. No. 10,463,683

ISOTOPOLOGUES OF 5-AZACYTIDINE

Celgene Corporation, Sum...

1. A compound of the formula:
or a pharmaceutically acceptable salt thereof, wherein:
Y1 is a hydrogen isotopically enriched with deuterium, and Y2, Y3, Y4, Y5, Y6, and Y7 are non-enriched hydrogen atoms.
US Pat. No. 10,449,187

FORMULATIONS OF 2-(4-CHLOROPHENYL)-N-((2-(2,6-DIOXOPIPERIDIN-3-YL)-1-OXOISOINDOLIN-5-YL)METHYL)-2,2-DIFLUOROACETAMIDE

Celgene Corporation, Sum...

1. A method of treating a cancer comprising administering to a mammal having cancer a lyophilized formulation comprising: Compound 1 (2-(4-chlorophenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2,2-difluoroacetamide), or a stereoisomer or mixture of stereoisomers, pharmaceutically acceptable salt, tautomer, prodrug, solvate, hydrate, co-crystal, clathrate, or polymorph thereof, a buffer and a bulking agent, wherein the cancer is a solid tumor and the method further comprises administering calcium, calcitriol, and vitamin D supplementation.

US Pat. No. 10,385,037

4?-O-SUBSTITUTED ISOINDOLINE DERIVATIVES AND COMPOSITIONS COMPRISING AND METHODS OF USING THE SAME

Celgene Corporation, Sum...

1. A compound having the formula:or a pharmaceutically acceptable salt, solvate, clathrate, or stereoisomer thereof.

US Pat. No. 10,357,489

ANTIPROLIFERATIVE COMPOUNDS AND METHODS OF USE THEREOF

Celgene Corporation, Sum...

1. A compound, wherein the compound is Compound 1of formulaor an enantiomer, mixture of enantiomers, tautomer, isotopolog, or pharmaceutically acceptable salt thereof.
US Pat. No. 10,272,117

METHODS OF USING AN ACTIVATOR OF CEREBLON FOR NEURAL CELL EXPANSION AND THE TREATMENT OF CENTRAL NERVOUS SYSTEM DISORDERS

Celgene Corporation, Sum...

1. A method for assessing efficacy of a Bromodomain Containing 7 (BRD7) antagonist or an Ikaros antagonist in treating a central nervous system (CNS) cell defective disease, disorder or condition, or a symptom thereof, in a patient, comprising:(i) administering the BRD7 antagonist or Ikaros antagonist to the patient; and
(ii)(A) comparing a CNS cell mass in the patient before and after administration of the BRD7 antagonist or Ikaros antagonist,
wherein an increase in CNS cell mass after administration of the BRD7 antagonist or Ikaros antagonist as compared to before administration of the BRD7 antagonist or Ikaros antagonist is indicative of the efficacy of the BRD7 antagonist or Ikaros antagonist in treating the CNS-cell defective disease, disorder or condition, or symptom thereof; or
(ii)(B) comparing expression level of a Yamanaka factor, Nanog, NeuroD, Zic3, Elavl3, and/or a BAM factor in the patient before and after administration of the BRD7 antagonist or Ikaros antagonist, wherein an increase in the expression levels of the Yamanaka factor, Nanog, NeuroD, Zic3, Elavl3, and/or BAM factor after administration of the BRD7 antagonist or Ikaros antagonist as compared to before administration of the BRD7 antagonist or Ikaros antagonist is indicative of the efficacy of the BRD7 antagonist or Ikaros antagonist in treating the CNS-cell defective disease, disorder or condition, or symptom thereof.

US Pat. No. 10,266,514

PROCESSES FOR THE PREPARATION OF 4-AMINO-2-(2,6-DIOXOPIPERIDIN-3-YL)ISOINDOLINE-1,3-DIONE COMPOUNDS

Celgene Corporation, Sum...

1. A process for preparing a compound of Formula (I):
or a pharmaceutically acceptable free amine, salt, or stereoisomer thereof, comprising the step of cyclizing a compound of Formula (II) or (IIA):

or a salt thereof with a cyclizing agent of Formula (V):

wherein R1 is H, F, benzyl, (C1-C8)alkyl, (C2-C8)alkenyl, or (C2-C8)alkynyl; and each of X and Y is independently an unsubstituted or substituted imidazolyl, benzimidazolyl or benzotriazolyl;
wherein, the compound of Formula (II) or (IIA) is prepared by reducing a compound of Formula (III) or (IIIA) respectively:

with a reducing agent.