US Pat. No. 9,066,948

OXADIAZOLO[3,2-A]PYRIMIDINES AND THIADIAZOLO[3,2-A]PYRIMIDINES

THE UNITED STATES OF AMER...

6. A pharmaceutical composition comprising a compound according to claim 1, in combination or association with a pharmaceutically acceptable diluent or carrier.

US Pat. No. 9,133,461

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF THE ALAS1 GENE

Alnylam Pharmaceuticals, ...

1. A double-stranded ribonucleic acid (dsRNA) for inhibiting expression of ALAS1, wherein said dsRNA comprises a sense strand
and an antisense strand, wherein:
(i) the antisense strand is complementary to at least nucleotides 871-889 of SEQ ID NO:1 and comprises SEQ ID NO:1296,
(ii) the sense strand comprises at least 15 contiguous nucleotides from SEQ ID NO:1295,
(iii) a ligand and linker with a structure as shown below is attached to the 3? end of the sense strand of the dsRNA
and
(iv) the dsRNA comprises one or more nucleotides with a modification chosen from a 2?-O-methyl modified nucleotide, a 2?-fluoro
modified nucleotide, or both.

US Pat. No. 9,303,044

7-(PIPERAZIN-1-YL)-5H-[1,3,4]THIADIAZOLO[3,2-A]PYRIMIDIN-5-ONES FOR THE TREATMENT OF THROMBOTIC DISORDERS

THE UNITED STATES OF AMER...

10. A pharmaceutical composition comprising the compound of claim 1, in combination or association with a pharmaceutically acceptable diluent or carrier.
US Pat. No. 9,492,514

CERAMIDE LEVELS IN THE TREATMENT AND PREVENTION OF INFECTIONS

Icahn School of Medicine ...

1. A method for improving pathogenic clearance in a subject having Cystic Fibrosis, COPD, and/or an open wound, said method
comprising:
selecting a subject having Cystic Fibrosis, COPD, and/or an open wound and
administering to said selected subject a therapeutically effective amount of ceramidase under conditions effective to reduce
ceramide and improve pathogenic clearance of a Pseudomonas pathogen in said selected subject.

US Pat. No. 9,217,136

CHIMERIC NEWCASTLE DISEASE VIRUSES AND USES THEREOF

Icahn School of Medicine ...

1. A chimeric Newcastle disease virus (NIV), comprising a packaged genome which encodes a heterologous interferon antagonist
and a modified F protein with a mutated cleavage site, wherein the heterologous interferon antagonist and the modified F protein
are expressed by the virus.
US Pat. No. 9,114,139

DOSE ESCALATION ENZYME REPLACEMENT THERAPY FOR TREATING ACID SPHINGOMYELINASE DEFICIENCY

Icahn School of Medicine ...

1. A method for reducing sphingomyelin accumulation in one or more organs of a human subject having an acid sphingomyelinase
deficiency (ASMD), comprising:
(a) administering at least one initial dose of recombinant human acid sphingomyelinase (rhASM) to the human subject, wherein
the initial dose is from 0.025 mg/kg to 0.275 mg/kg; and

(b) subsequent to the administration of the at least one initial dose, administering a higher dose of rhASM to the human subject,
wherein the higher dose is from 0.1 mg/kg to 3.0 mg/kg higher than the initial dose.

US Pat. No. 9,631,193

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF THE ALAS1 GENE

ALNYLAM PHARMACEUTICALS, ...

1. A method of treating a disorder related to ALAS1 expression, comprising administering to a subject in need of such treatment
a therapeutically effective amount of a double-stranded ribonucleic acid (dsRNA), wherein said dsRNA comprises a sense strand
and an antisense strand, each of which are 15-30 nucleotides in length, wherein the antisense strand comprises a region of
complementarity to an ALAS1 RNA and comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from
SEQ ID NO: 1296, and wherein the antisense strand is complementary to at least nucleotides 871-889 of SEQ ID NO: 1.
US Pat. No. 9,655,954

DOSE ESCALATION ENZYME REPLACEMENT THERAPY FOR TREATING ACID SPHINGOMYELINASE DEFICIENCY

Icahn School of Medicine ...

1. A method for reducing sphingomyelin accumulation in one or more organs of a human subject having an acid sphingomyelinase
deficiency (ASMD), comprising:
(a) administering at least one initial dose of recombinant human acid sphingomyelinase (rhASM) to the human subject, wherein
the initial dose is 0.3 mg/kg; and

(b) subsequent to the administration of the at least one initial dose, administering a higher dose of rhASM to the human subject
if the human subject has a total bilirubin concentration of less than or equal to 2.1 mg/dL and the human subject does not
experience a severe related adverse event, wherein the higher dose is from 0.1 mg/kg to 3.0 mg/kg higher than the initial
dose.

US Pat. No. 9,321,772

SUBSTITUTED PYRAZOLO[3,4-D]PYRIMIDINES AND USES THEREOF

The Regents of the Univer...

1. A compound having the formula:

wherein
R1 and R2 are independently hydrogen or substituted or unsubstituted alkyl;

R3 is independently substituted or unsubstituted alkyl;

R5 is independently
halogen, —CN, —CXa3, —S(O)2H, —NO, —NO2, —C(O)H, —C(O)NH2, —S(O)2NH2, —OH, —SH, —SO2Cl, —SO3H, —SO4H, —NHNH2, —ONH2, —NHC?(O)NHNH2, —NHC?(O)NH2, —NHSO2H, —NHC?(O)H, —NHC(O)—OH, —NHOH, —OCF3, —OCHF2, —CO2H, or substituted or unsubstituted (C1-C6) alkyl;
R6 is independently
halogen, —CN, —CXb3, —S(O)2H, —NO, —NO2, —C(O)H, —C(O)NH2, —S(O)2NH2, —OH, —SH, —SO2Cl, —SO3H, —SO4H, —NHNH2, —ONH2, —NHC?(O)NHNH2, —NHC?(O)NH2, —NHSO2H, —NHC?(O)H, —NHC(O)—OH, —NHOH, —OCF3, —OCHF2, or —CO2H;
L1 is independently a bond or substituted or unsubstituted alkylene;

z1 is independently an integer from 0 to 4;
z2 is independently an integer from 2 to 5; and
Xa and Xb are independently —F, —Cl, —Br, or —I.

US Pat. No. 9,200,076

USE OF FSH RECEPTOR LIGANDS FOR DIAGNOSIS AND THERAPY OF CANCER

INSERM (INSTITUT NATIONAL...

1. A method for collecting imaging data, the method comprising administering a patient an imaging agent comprising a detectably
labeled follicle stimulating hormone (FSH) receptor ligand; and collecting imaging data in said patient.
US Pat. No. 9,539,220

METHODS FOR TREATING SUICIDAL IDEATION

Icahn School of Medicine ...

1. A method of treating recurrent thoughts of death, suicidal ideation or suicidal attempts, consisting of intranasally administering
to a patient who suffers from at least one of said recurrent thoughts of death, suicidal ideation or suicidal attempts a composition
consisting of ketamine at a dosage sufficient to alleviate said recurrent thoughts of death, suicidal ideation or suicidal
attempts and at least one pharmaceutically acceptable excipient.
US Pat. No. 9,322,064

NUCLEIC ACIDS, METHODS AND KITS FOR THE DIAGNOSIS OF DYT6 PRIMARY TORSION DYSTONIA

Icahn School of Medicine ...

1. A method for detecting the presence of a THAP1 mutation in a biological sample from a human subject, comprising:
(a) obtaining a biological sample from a human subject;
(b) contacting a THAP1 nucleic acid coding sequence in a biological sample with an oligonucleotide that specifically hybridizes
to a human THAP1 nucleic acid sequence comprising a c.86G>C mutation of SED ID NO:4. and

(c) detecting hybridization of the THAP1 nucleic acid with the oligonucleotide, wherein detecting hybridization is indicative
of a mutation of THAP1 nucleic acid in a biological sample from a human subject and wherein the mutation is c86G>C of SEQ
ID NO:4.

US Pat. No. 9,592,207

INTRANASAL ADMINISTRATION OF KETAMINE TO TREAT DEPRESSION

Icahn School of Medicine ...

1. A method of treating depression comprising intranasally administering a dose of ketamine effective to alleviate depression
to a patient afflicted with depression that has not responded to at least two adequate antidepressant treatments.
US Pat. No. 9,655,953

TARGETED PROTEIN REPLACEMENT FOR THE TREATMENT OF LYSOSOMAL STORAGE DISORDERS

Icahn School of Medicine ...

1. A nucleic acid comprising a nucleotide sequence encoding a fusion protein comprising a mammalian acid sphingomyelinase
or active fragment thereof covalently attached to a targeting moiety, wherein the targeting moiety binds to an extracellular
portion of Intracellular Adhesion Molecule-1 (ICAM-1) or Platelet Endothelial Cell Adhesion Molecule (PECAM-1).
US Pat. No. 9,254,273

COMPOSITIONS AND METHODS FOR TREATING ALZHEIMER'S DISEASE AND RELATED DISORDERS AND PROMOTING A HEALTHY NERVOUS SYSTEM

Icahn School of Medicine ...

1. A method of treating an individual identified as being at risk of developing Alzheimer's disease comprising providing said
identified individual with D-pinitol in an amount and for a sufficient period of time, to reduce the likelihood that said
identified individual will develop said Alzheimer's disease, wherein the individual has a symptom of Non-Insulin Dependent
Diabetes Mellitus (NIDDM) or a symptom of cognitive impairment comprising a learning or memory deficit.
US Pat. No. 10,035,984

CHIMERIC NEWCASTLE DISEASE VIRUSES AND USES THEREOF

Icahn School of Medicine ...

1. A chimeric Newcastle disease virus (NDV), comprising a packaged genome which encodes a heterologous interferon antagonist, wherein the heterologous interferon antagonist is expressed by the virus, and wherein the packaged genome encodes a cytokine, and wherein the cytokine is expressed by the virus.

US Pat. No. 9,532,989

OXADIAZOLO[3,2-A]PYRIMIDINES AND THIADIAZOLO[3,2-A]PYRIMIDINES

THE UNITED STATES OF AMER...

1. A method for the treatment of a thrombotic disorder comprising administering to a subject having a thrombotic disorder
or at risk of thrombotic disorder an effective amount of a compound according to Formula P-I, in free or pharmaceutically
acceptable salt form, or a pharmaceutical composition comprising a compound of Formula P-I and a pharmaceutically acceptable
diluent or carrier, such that platelet aggregation and/or adhesion is reduced; wherein Formula P-I is:
wherein:
i) A is S, N(H), CH2, or O;

ii) R1 is:

phenyl optionally substituted with one or more nitro, —C(O)N(R5)(R6) and/or —N(R5)(R6), and Y is a —C1-C4alkylene or arylene;

phenyl substituted with one or more nitro and/or —N(R5)(R6), and Y is a single bond;

phenyl substituted with —C(O)OR3 and Y is a —C1-C4alkylene or arylene;

heteroaryl wherein said heteroaryl group is optionally substituted with one or more —C1-C4alkyl, and Y is a single bond or —C1-C4alkylene;

heteroaryl wherein said heteroaryl group is substituted with halo, —C(O)OH, —CH2C(O)OH, or —NH2, and Y is arylene;

pyrazolyl, isoxazolyl, furyl or thienyl and Y is arylene wherein said pyrazolyl, isoxazolyl, furyl or thienyl is optionally
substituted with one or more —C1-C4alkyl, —C0-4alkyl-C(O)OH, —N(R13)(R14), or halo; or

—C(O)N(R4)(CH2)1-4—C(O)OR3 and Y is a single bond, —C1-C4alkylene or arylene,

—C(O)N(R4)(CH2)1-4—N(R13)(R14) and Y is a single bond, —C1-C4alkylene or arylene;

—N(R4)—C(O)-heteroaryl wherein said heteroaryl is optionally substituted with halo and Y is a single bond, —C1-C4alkylene, or arylene;

—N(R4)—C1-4alkylene-heteroaryl and Y is a single bond, —C1-C4alkylene, or arylene;

—N(R10)—C(O)—[C(R11)(R12)]1-4—N(R13)(R14) and Y is a single bond, —C1-C4alkylene, or arylene;

—N(R10)—C(O)—C3-10heterocycloalkyl and Y is a single bond, —C1-C4alkylene or arylene;

—N(R4)(CH2)1-4—C(O)OR4 and Y is C1-C4alkylene or arylene;

—N(R4)C(O)C(H)(NH2)CH2CH2—C(O)OR3 and Y is arylene;

—N(R4)C(O)C(H)(NH2)CH2-heteroaryl and Y is arylene;

—N(R4)C(O)C(H)(CH3)—NH2 and Y is arylene;

—N(R4)C(O)CH2CH2C(H)(NH2)—COOH and Y is arylene;

—N(R4)C(O)—C(H)(NH2)CH2CH2—COOH and Y is arylene; or

—N(R4)C(O)-heteroaryl (—N(H)C(O)isoxazolyl) and Y is arylene;

iii) R2 is H, halo or —C1-C4alkyl;

iv) Ra, Ra?, Rb, Rb?, Rc, Rd, Rd?, Re, and Re? are independently H or C1-C4alkyl;

v) R3, R4, R5 and R6 are independently H or C1-C4alkyl;

vi) R10, R11, R12, R13 and R14 are independently H or C1-4alkyl.

US Pat. No. 9,314,484

METHODS AND COMPOSITIONS FOR CANCER IMMUNOTHERAPY USING FLAGELLIN-TUMOR ASSOCIATED ANTIGEN FUSION PROTEIN EXPRESSING TUMOR CELLS

Icahn School of Medicine ...

3. A method for treating a cancer in a patient in need of such treatment comprising administering to said patient a composition
comprising a tumor cell expressing a fusion protein, wherein said fusion protein comprises:
a flagellin or fragment thereof and a tumor associated antigen (TAA), in an effective amount for eliciting an anti-tumor immune
response,

wherein the flagellin or fragment thereof is capable of binding to one or more of Toll-like receptor-5 (TLR5), Naip5 or Ipaf.
US Pat. No. 9,233,154

T-HELPER CELL TYPE 17 LINEAGE-SPECIFIC ADJUVANTS, COMPOSITIONS AND METHODS

Icahn School of Medicine ...

1. A method for generating a TH17-inducing dendritic cell (DC) that secretes interleukin-6 (IL-6) and transforming growth factor beta (TGF-?), wherein the
combined amount of IL-6 and TGF-? secreted by the TH17-inducing DC is effective for inducing a TH17 response when the TH17-inducing DC is administered to a subject, the method comprising administering to a DC in vitro a Toll-like receptor (TLR)
agonist and an apoptotic cell-associated agent in a combined amount effective for generating the TH17-inducing DC.
US Pat. No. 9,494,572

METHOD AND COMPOSITIONS FOR TREATING CANCER AND RELATED METHODS

Icahn School of Medicine ...

1. A method for treatment of neoplastic disease comprising administering a subject suffering from said neoplastic disease
a first amount of an anti epidermal growth factor receptor (anti-EGFR) agent and one or both of a second amount of an agent
that increases activity of Krüppel-like factor 6 (KLF6) and/or a third amount of an agent that increases activity of transcription
factor forkhead box O1 (FOXO1) wherein said first and said second and/or third amounts together comprise a therapeutically
effective amount of an active combination of agents to treat said neoplastic disease.
US Pat. No. 9,387,242

CHIMERIC VIRUSES PRESENTING NON-NATIVE SURFACE PROTEINS AND USES THEREOF

Icahn School of Medicine ...

1. A chimeric Newcastle Disease Virus (NDV), comprising a packaged genome comprising a nucleotide sequence encoding an F-fusion
protein, wherein the F-fusion protein comprises the transmembrane and cytoplasmic domains of an NDV F protein and at least
one epitope of an ectodomain of a protective antigen of an infectious agent other than NDV or an antigen associated with a
disease that is anchored by the C-terminus of the antigen, so that the F-fusion protein is expressed and incorporated into
the chimeric NDV, and wherein the antigen is not a paramyxovirus antigen.
US Pat. No. 9,352,006

METHODS AND COMPOSITIONS FOR TREATING TUMORS USING MYELOID DERIVED SUPPRESSOR CELLS

Icahn School of Medicine ...

1. A composition comprising an isolated myeloid derived suppressor cell (MDSC) loaded with an oncolytic virus.
US Pat. No. 9,217,157

RECOMBINANT INFLUENZA VIRUSES AND USES THEREOF

Icahn School of Medicine ...

1. A pathogenic recombinant influenza virus comprising a nucleic acid sequence comprising a modified influenza virus nonstructural
(NS) gene segment or the complement thereof, wherein the modified influenza virus NS gene segment comprises in 3? to 5? order:
(a) (i) an influenza virus nonstructural protein 1 (NS1) open reading frame (ORF) lacking a stop codon, (ii) a heterologous
nucleotide sequence encoding a detectable substance, (iii) a cleavage site, and (iv) an influenza virus nuclear export protein
(NEP) ORF, wherein the modified influenza virus NS gene segment has one or more mutations in either the splice acceptor site,
the splice donor site, or both the splice acceptor and splice donor sites that prevents splicing of mRNA, and wherein the
modified influenza virus NS gene segment encodes (1) a fusion protein comprising NS1 and the detectable substance and (2)
a protein comprising NEP; or

(b) (i) an influenza virus NS1 ORF lacking a stop codon, (ii) a linker, (iii) a heterologous nucleotide sequence encoding
a detectable substance, (iv) a cleavage site, and (v) an influenza virus NEP ORF, wherein the modified influenza virus NS
gene segment has one or more mutations in either the splice acceptor site, the splice donor site, or both the splice acceptor
and splice donor sites that prevents splicing of mRNA, and wherein the modified influenza virus NS gene segment encodes (1)
a fusion protein comprising NS1, the amino acids encoded by the linker, and the detectable substance, and (2) a protein comprising
NEP.

US Pat. No. 9,216,189

ANTIBODIES WHICH BIND TYPE I CANNABINOID RECEPTOR/ANGIOTENSIS II RECEPTOR HETEROMERS

Icahn School of Medicine ...

1. An isolated monoclonal antibody which specifically binds to a type I cannabinoid receptor (CB1R)/angiotensin II receptor (AT1R) heteromer.

US Pat. No. 9,096,585

ANTIVIRAL COMPOUNDS AND USES THEREOF

Icahn School of Medicine ...

1. A method of treating or managing a viral infection, or preventing, treating or managing a pathological state resulting
from a viral infection in a human subject comprising administering to a human subject in need thereof an effective amount
of a compound of formula A3-H:

or a pharmaceutically acceptable salt, or stereoisomer thereof, wherein:
R1 and R2 are at each occurrence independently a C1-C8 alkyl group; or

R1 and R2, together with the nitrogen atom R1 and R2 are bound to, form a 3 to 10membered heterocyclic ring; and

R3 is substituted or unsubstituted indole, wherein the viral infection is a positive-sens, single-stranded RNA virus infection,
and wherein the virus is a member of flavivirus family.

US Pat. No. 9,352,033

METHODS FOR THE PROPAGATION OF MODIFIED INFLUENZA VIRUSES IN EMBRYONATED EGGS

Icahn School of Medicine ...

1. A method for vaccine production comprising:
(a) propagating in an embryonated chick egg six to nine days old a genetically engineered, attenuated influenza virus, in
which the genome of the attenuated influenza virus encodes a truncated NS1 protein of between 90 and 130 amino acid residues
of the first N-terminal 90 to 130 amino acid residues of an NS1 protein of the same or a different influenza virus strain,
so that the genetically engineered, attenuated influenza virus expresses the truncated NS1 protein and has an impaired interferon
antagonist phenotype, wherein the N-terminal amino acid of the NS1 protein of the same or a different influenza virus strain
is 1, and wherein the influenza virus is not influenza C virus; and

(b) collecting progeny virus,
wherein the virus is grown to sufficient quantities and under conditions that are free from contamination, such that the progeny
virus is suitable for formulation into a vaccine.

US Pat. No. 9,387,240

ATTENUATED NEGATIVE STRAND VIRUSES WITH ALTERED INTERFERON ANTAGONIST ACTIVITY FOR USE AS VACCINES AND PHARMACEUTICALS

Icahn School of Medicine ...

1. A genetically engineered attenuated influenza virus, the genome of which encodes a truncated NS1 that is between 90 and
100 amino acid residues of the first N-terminal 90 to 100 amino acid residues of an NS1 protein of an influenza virus strain,
so that the genetically engineered influenza virus expresses the truncated NS1 protein and has an impaired interferon antagonist
phenotype, wherein the N-terminal amino acid of the NS1 protein of the influenza virus strain is 1.
US Pat. No. 9,371,366

INFLUENZA VIRUS VACCINES AND USES THEREOF

Icahn School of Medicine ...

1. A chimeric influenza virus hemagglutinin (HA) polypeptide comprising:
(a) the stem domain of the HA from influenza virus A/California/4/2009 (H1N1) and the globular head domain of the HA from
an A/Vietnam/1203/2004 (H5), A/Indonesia/5/2005 (H5), A/Anhui/1/2005 (H5), A/Bar headed goose/Quinghai/1A/2005 (H5), A/turkey/Turkey/1/2005
(H5), or A/Whooperswan/Mongolia/244/2005 (H5) influenza virus;

(b) the stem domain of the HA from influenza virus A/Victoria/361/2011 (H3N2), A/harbor seal/Massachusetts/1/2011 (H3N8),
or A/Indiana/10/2011 (H3N2) and the globular head domain of the HA from an influenza virus of the H5 subtype;

(c) the stem domain of the HA from influenza virus A/Victoria/361/2011 (H3N2), A/harbor seal/Massachusetts/1/2011 (H3N8),
or A/Indiana/10/2011 (H3N2) and the globular head domain of the HA from an influenza virus of the H7 subtype;

(d) the stem domain of the HA from influenza virus B/Malaysia/2506/2004, B/Florida/4/2006, B/Wisconsin/1/2010, or B/Brisbane/60/2008
and the globular head domain of the HA from an influenza virus of the H5 subtype;

(e) the stem domain of the HA from influenza virus B/Malaysia/2506/2004, B/Florida/4/2006, B/Wisconsin/1/2010, or B/Brisbane/60/2008
and the globular head domain of the HA from an influenza virus of the H7 subtype; or

(f) the stem domain of the HA from influenza virus B/Malaysia/2506/2004, B/Florida/4/2006, B/Wisconsin/1/2010, or B/Brisbane/60/2008
and the globular head domain of the HA from a different strain of influenza B virus.

US Pat. No. 9,481,896

STEM CELL GENE TARGETING

ICAHN SCHOOL OF MEDICINE ...

1. A method for modifying a human Rosa26 gene in an isolated human stem cell, which method comprises introducing an expression
cassette comprising a nucleic acid sequence encoding a protein, such that said nucleic acid sequence is operatively linked
to a promoter heterologous to the human Rosa26 gene, or the endogenous human Rosa26 promoter.

US Pat. No. 9,265,780

METHOD OF ENHANCING LYSOSOMAL ?-GALACTOSIDASE A

ICAHN SCHOOL OF MEDICINE ...

1. A method of enhancing the activity of lysosomal ?-galactosidase A in mammalian cells comprising administering to a mammalian
subject in need thereof an effective amount of at least one calystegine compound represented by the formula:
wherein
R1 is H or CH3;

R2 is OH or H;

R3 is H or OH; and

R4 is H or OH.

US Pat. No. 9,175,069

MONOCLONAL ANTIBODIES AGAINST INFLUENZA VIRUS GENERATED BY CYCLICAL ADMINISTRATION AND USES THEREOF

Icahn School of Medicine ...

1. A hybridoma
(a) designated 7A7 deposited under provisions of the Budapest Treaty with the American Type Culture Collection (ATCC, 10801
University Blvd., Manassas, Va. 20110-2209) on May 22, 2009 (ATCC Accession No. PTA-10058),

(b) designated 12D1 deposited under provisions of the Budapest Treaty with the American Type Culture Collection (ATCC, 10801
University Blvd., Manassas, Va. 20110-2209) on May 22, 2009 (ATCC Accession No. PTA-10059),

(c) designated 39A4 deposited under provisions of the Budapest Treaty with the American Type Culture Collection (ATCC, 10801
University Blvd., Manassas, Va. 20110-2209) on May 22, 2009 (ATCC Accession No. PTA-10060), or

(d) designated 66A6 deposited under provisions of the Budapest Treaty with the American Type Culture Collection (ATCC, 10801
University Blvd., Manassas, Va. 20110-2209) on May 26, 2010 (ATCC Accession No. PTA-11046).

US Pat. No. 9,155,784

ANTI-TNF-? THERAPY FOR THE MUCOPOLYSACCHARIDOSES AND OTHER LYSOSOMAL DISORDERS

Icahn School of Medicine ...

1. A method of treating a subject with a lysosomal storage disorder, said method comprising:
selecting a subject with a lysosomal storage disorder and
administering to the selected subject an agent for an enzyme replacement therapy, and an agent for an anti-TNF-? treatment
under conditions effective to treat the lysosomal storage disorder in the selected subject.

US Pat. No. 9,051,359

INFLUENZA VIRUS VACCINES AND USES THEREOF

Icahn School of Medicine ...

1. A vaccine comprising a polypeptide, wherein said polypeptide comprises:
a. an influenza hemagglutinin HA1 domain that comprises an HA1 N-terminal stem segment covalently linked to a linker of 1
to 50 heterologous residues that is in turn covalently linked to an HA1 C-terminal stem segment; said HA1 domain in tertiary
or quaternary association with

b. an influenza hemagglutinin HA2 domain, andwherein the vaccine induces antibodies which are cross-reactive among HA subtypes.
US Pat. No. 9,844,592

BACTERIAL RNAS AS VACCINE ADJUVANTS

ICAHN SCHOOL OF MEDICINE ...

1. A vaccine composition comprising a nonviable immunogen and an adjuvant, wherein said adjuvant comprises at least one of
an mRNA of prokaryotic origin and an RNA of prokaryotic origin, wherein the RNA has structural features comprising a 3? stem-loop
structure, at least one of intramolecular base-pairing and nucleotide modifications, no 5? cap, no 5? tri-phosphate group
and no 3? poly(A) tail, and wherein the immunogen is an extracellular pathogen.
US Pat. No. 9,549,975

GENETICALLY ENGINEERED SWINE INFLUENZA VIRUS AND USES THEREOF

Icahn School of Medicine ...

1. A genetically engineered attenuated swine influenza virus having an impaired interferon antagonist phenotype, wherein the
virus comprises a swine influenza virus NS1 gene with a mutation resulting in a swine influenza virus NS1 protein having a
deletion of between 90 and 94 amino acid residues from the carboxy-terminus of NS1, wherein the swine influenza virus NS1
gene is from A/Swine/Texas/4199-2/98.
US Pat. No. 9,134,297

METHOD AND COMPOSITIONS FOR TREATING CANCER AND RELATED METHODS

Icahn School of Medicine ...

1. A method of enhancing sensitivity to an anti epidermal growth factor receptor (anti-EGFR) agent comprising administering
to a subject in need thereof a first agent, wherein said first agent increases activity of Krüppel-like factor 6 (KLF6) in
an amount effective for said enhancing sensitivity to said anti-EGFR agent.
US Pat. No. 9,540,612

METHODS FOR PROGRAMMING DIFFERENTIATED CELLS INTO HEMATOPOIETIC STEM CELLS

Icahn School of Medicine ...

1. A method for programming a differentiated cell into a hematopoietic stem cell, the method comprising introducing a combination
of transcription factors in the differentiated cell, wherein the combination comprises GATA binding protein 2 (GATA2), growth
factor independent 1B (GFI1B), and c-Fos.

US Pat. No. 9,724,328

METHODS AND COMPOSITIONS FOR TREATMENT OF LIPID STORAGE DISORDERS

Icahn School of Medicine ...

1. A method comprising: administering to a subject with a lipid storage disorder a pharmaceutically effective amount of bryostatin
1.

US Pat. No. 9,540,358

TRICYCLIC COMPOUNDS AS ANTICANCER AGENTS

ICAHN SCHOOL OF MEDICINE ...

1. A compound of formula (I):

wherein:
X is selected from the group consisting of: —(CH2—CH2)—, and —CH?CH—;

Y is

R1, R2, R3, and R4 are independently selected from the group consisting of: H, halo, —N3, —NR6R7, (C1-C6)alkyl, (C1-C6)haloalkyl, —OR6, —C(O)R6, —OC(O)R6, —C(O)NR6R7, —C(O)OR6, —SR6, —SO2R6, and —SO2NR6R7;

R5 is —(CR15R16)p-Qq-(CR15R16)n-p—Z or


Q is chosen from —O—, —NR14— and


each R6 and R7 is independently selected from the group consisting of: H and (C1-C6)alkyl;

R14 is H or (C1-C3)alkyl;

R15 and R16, in each occurrence are chosen independently from H, OH, cyano, amino, (C1-C3)alkylamino, (C1-C3)dialkylamino, (C1-C3)alkyl, (C1-C3)haloalkyl, (C1-C3)haloalkoxy, and (C1-C3)alkoxy, or, taken together, two of R14, R15 and R16 may form a three to seven membered non-aromatic carbocycle or heterocycle wherein said three to seven membered carbocycle
or heterocycle may be additionally substituted with one or two substituents chosen from OH, F, cyano, amino, (C1-C3)alkylamino, (C1-C3)dialkylamino, (C1-C3)alkyl, (C1-C3)haloalkyl, (C1-C3)haloalkoxy, and (C1-C3)alkoxy;

n is an integer from 2 to 4;
p is zero, 1 or 2;
q is zero or 1;
t is zero, 1 or 2;
u is 2;
v is 1, 2 or 3;
with the proviso that when q is zero and R15 and R16, in all of their occurrences are H, n is not 4;

Z is selected from the group consisting of: —NHSO2R17, —NHC(O)NR8R9, —S(O)2NR8R9, substituted or unsubstituted cyclic carbamate; substituted or unsubstituted cyclic urea, cyanoguanidine;

R8 and R9 are independently selected from H, substituted or unsubstituted (C1-C6)alkyl, and substituted or unsubstituted (C3-C7) cycloalkyl; and

R17 is chosen from phenyl and monocyclic heteroaryl, said phenyl and monocyclic heteroaryl optionally substituted with one or
two substituents chosen from OH, halogen, cyano, nitro, (C1-C3)alkylamino, (C1-C3)dialkylamino, (C1-C3)acylamino, (C1-C3)alkylsulfonyl, (C1-C3)alkylthio, (C1-C3)alkyl, (C1-C3)haloalkyl, (C1-C3)haloalkoxy, and (C1-C3)alkoxy.

US Pat. No. 9,072,822

SPINAL SHIELD IMPLANT AND TREATMENT OF SPINAL METASTASES

ICAHN SCHOOL OF MEDICINE ...

1. A radiation shield for use in treatment of a patient having spinal metastatic disease comprising:
a body that defines a hollow space that is configured to receive a spinal cord of the patient such that the body surrounds
the spinal cord of the patient, the body including an axially extendable section that is slidably adjustable along a surface
of the body so as to increase a surface area of the shield by extending the extendable section in a longitudinal direction
relative to the body and the spinal cord resulting in a greater length of the patient's spinal cord being shielded, the body
being shaped to accommodate spinal cord nerves when implanted.

US Pat. No. 10,131,695

INFLUENZA VIRUS VACCINES AND USES THEREOF

Icahn School of Medicine ...

1. A chimeric influenza virus hemagglutinin (HA) polypeptide comprising an HA stem domain and an HA globular head domain, wherein the HA globular head domain is from a different influenza virus subtype than the influenza virus subtype of the HA stem domain, wherein(a) the HA stem domain comprises (i) an HA1 N-terminal stem segment, wherein the HA1 N-terminal stem segment consists of amino acid residues HA1N-term through Ap; and (ii) an HA1 C-terminal stem segment, wherein the HA1 C-terminal stem segment consists of amino acid residues Aq through HA1C-term; and
(b) the HA globular head domain comprises the amino acid residues between Ap and Aq of an HA1 domain: and
wherein HA1N-term is the N-terminal amino acid of a mature HA0 protein lacking a signal peptide; wherein HA1C-term is the C-terminal amino acid of an HA1 domain; and wherein Ap is the Cys that corresponds to amino acid position 52 of an HA1 domain using H3 numbering; and wherein Aq is the Cys that corresponds to amino acid position 277 of an HA1 domain using H3 numbering.
US Pat. No. 9,855,290

ANTIBODIES WHICH BIND TYPE I CANNABINOID RECEPTOR/ANGIOTENSIN II RECEPTOR HETEROMERS AND METHODS OF USE

Icahn School of Medicine ...

1. A method of treating a liver fibrosis in a mammal, comprising administering to the mammal in need of such treatment an
effective amount of a monoclonal antibody that specifically binds to a type I cannabinoid receptor (CB1R)/angiotensin II receptor (AT1R) heteromer.
US Pat. No. 9,849,172

INFLUENZA VIRUS VACCINES AND USES THEREOF

Icahn School of Medicine ...

1. A method of inducing an immune response to an influenza virus hemagglutinin (HA) in a subject comprising administering
to a subject a vaccine comprising a polypeptide, wherein said polypeptide comprises:
(a) an influenza hemagglutinin HA1 domain that comprises an HA1 N-terminal stem segment covalently linked to a linker of 1
to 50 heterologous residues that is in turn covalently linked to an HA1 C-terminal stem segment; said HA1 domain in tertiary
or quaternary association with

(b) an influenza hemagglutinin HA2 domain,
wherein the vaccine induces antibodies which are cross-reactive among HA subtypes, and wherein said polypeptide comprises
a disulfide bridge between Ap and Aq, wherein Ap is Cys that corresponds to amino acid position 52 of an HA1 domain using H3 numbering and Aq is Cys that corresponds to amino acid position 277 of an HA1 domain using H3 numbering.

US Pat. No. 9,845,320

BENZOTHIAZOLE OR BENZOXAZOLE COMPOUNDS AS SUMO ACTIVATORS

Icahn School of Medicine ...

1. A method of treating heart failure in a patient in need thereof, comprising administering to said patient a therapeutically
effective amount of a compound of Formula II:
or a pharmaceutically acceptable salt thereof; wherein:
Ar is aryl or heteroaryl, each of which is optionally substituted with 1, 2, 3, 4, 5, or 6independently selected R1a groups;

W is S or O;
Y is S or O;
each X is independently CH or N;
Z is O, S, or NRA;

RA is H or C1-4 alkyl;

R1, R2, R3, and R4 are each independently selected from hydrogen, halo, CN, nitro, hydroxy, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, amino, C1-6 alkylamino, di-C1-4-alkylamino, carboxy, carbamyl, C1-6 alkylcarbamyl, di(C1-4 alkyl)carbamyl, C1-6 alkylcarbonyl, C1-6 alkoxycarbonyl, C1-6 alkylcarbonyloxy, C1-6 alkylsulfonyl, C1-6 alkylcarbonylamino, C1-6alkylsulfonylamino, aminosulfonyl, C1-6 alkylaminosulfonyl, di-C1-4 alkylaminosulfonyl, aminosulfonylamino, C1-6 alkylaminosulfonylamino, and di-C1-4 alkylaminosulfonylamino; wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkylamino, di-C1-4-alkylamino, C1-6 alkylcarbamyl, di(C1-4 alkyl)carbamyl, and C1-6 alkylcarbonyl are each optionally substituted with 1, 2, or 3 groups independently selected from halo, CN, hydroxy, C1-3alkoxy, amino, C1-3 alkylamino, and di-C1-3-alkylamino; and

each R1a is independently selected from halo, CN, nitro, hydroxy, C1-6 alkyl, C1-6haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C2-6 heterocycloalkyl, phenyl, C1-6heteroaryl, C1-6 alkoxy, C1-6 haloalkoxy, amino, C1-6 alkylamino,di-C1-4-alkylamino, carboxy, carbamyl, C1-6 alkylcarbamyl, di(C1-4 alkyl)carbamyl, C1-6 alkylcarbonyl, C1-6 alkoxycarbonyl, C1-6 alkylcarbonyloxy, C1-6 alkylsulfonyl, C1-6 alkylcarbonylamino, C1-6 alkylsulfonylamino, aminosulfonyl, C1-6 alkylaminosulfonyl, di-C1-4 alkylaminosulfonyl, aminosulfonylamino, C1-6alkylaminosulfonylamino, and di-C1-4 alkylaminosulfonylamino; wherein said C1-6 alkyl, C1-6haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C2-6 heterocycloalkyl, phenyl, C1-6 heteroaryl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkylamino, C1-6 alkylcarbamyl, di(C1-4 alkyl)carbamyl, and C1-6 alkylcarbonyl are each optionally substituted with 1, 2, or 3groups independently selected from halo, CN, hydroxy, C1-3 alkoxy, amino, C1-3 alkylamino, and di-C1-3-alkylamino; or

two adjacent R1a taken together with the atoms to which they are attached can form a 3-7membered carbocyclic or 4-6 membered heterocyclic ring,
each of which is optionally substituted with 1, 2, 3, or 4 C1-3 alkyl groups.

US Pat. No. 9,745,553

MESODERM AND DEFINITIVE ENDODERM CELL POPULATIONS

ICAHN SCHOOL OF MEDICINE ...

1. A method of making a cell population enriched for hepatocytes comprising the steps of (a) culturing pluripotent stem cells
in the presence of activin to induce differentiation into endoderm lineages, (b) further culturing the cells of step (a) in
the presence of BMP-4 and bFGF and in the absence of serum to induce differentiation into a hepatic lineage, and (c) culturing
the cells from step (b) with one or more cytokines that promote hepatocyte growth to produce a population enriched for hepatocytes.
US Pat. No. 9,714,424

RNAI INHIBITION OF USP10 TO TREAT OCULAR DISORDERS

ICAHN SCHOOL OF MEDICINE ...

1. A method of attenuating expression of USP10 mRNA in an eye of a subject in an area of ocular wound healing, said method
comprising: administering to said eye of said subject a composition comprising an effective amount of siRNA directed against
USP10 mRNA or a plurality of siRNA directed against USP10 mRNA consisting of a length of 19 to 49 nucleotides and a pharmaceutically
acceptable carrier wherein the expression of USP10 mRNA is attenuated resulting in the degradation of one or more ?v integrin
proteins that are present and which degradation thereby results in inhibiting the persistence of myofibroblasts;
whereby scarring that would result in the absence of application of the siRNA directed against USP10 mRNA or the plurality
of siRNA directed against USP10 mRNA is reduced.

US Pat. No. 9,908,930

ANTIBODIES AGAINST INFLUENZA VIRUS HEMAGGLUTININ AND USES THEREOF

ICAHN SCHOOL OF MEDICINE ...

1. A monoclonal antibody that binds to a hemagglutinin of an influenza A virus strain of the H1 subtype, wherein the antibody
comprises
(a) a variable heavy (VH) domain having the amino acid sequence of SEQ ID NO:17;
(b) a variable light (VL) domain having the amino acid sequence of SEQ ID NO:25;
(c) a VH domain having the amino acid sequence of SEQ ID NO 17 and a VL domain having the amino acid sequence of SEQ ID NO:25;
or

(d) a VH complementarity determining region (CDR)1, VH CDR2, a VH CDR3 domain, a VL CDR1, a VL CDR2, and a VL CDR3 having
the amino acid sequences of SEQ ID NO:19, 21, 23, 27, 29 and 31, respectively.

US Pat. No. 9,796,717

TRICYCLIC HETEROCYCLES AS ANTICANCER AGENTS

ICAHN SCHOOL OF MEDICINE ...

1. A compound of formula (I):

R1, R2, R3, and R4 are independently selected from the group consisting of: H, halo, —N3, —NR6R7, (C1-C6)alkyl, (C1-C6)haloalkyl, —OR6, —C(O)R6, —OC(O)R6, —C(O)NR6R7, —C(O)OR6, —SR6, —SO2R6, and —SO2NR6R7;

R5 is —(CR15R16)p-Qq-(CR15R16)n-p—Z or


Q is chosen from —O—, —NR14— and


each R6 and R7 is independently selected from the group consisting of: H and (C1-C6)alkyl;

R14 is H or (C1-C3)alkyl;

R15 and R16, in each occurrence are chosen independently from H, OH, cyano, amino, (C1-C3)alkylamino, (C1-C3)dialkylamino, (C1-C3)alkyl, (C1-C3)haloalkyl, (C1-C3)haloalkoxy, and (C1-C3)alkoxy, or, taken together, two of R15 and R16 may form a three to seven membered heterocycle or non-aromatic carbocycle, wherein said three to seven membered carbocycle
or heterocycle may be additionally substituted with one or two substituents chosen from OH, F, cyano, amino, (C1-C3)alkylamino, (C1-C3)dialkylamino, (C1-C3)alkyl, (C1-C3)haloalkyl, (C1-C3)haloalkoxy, and (C1-C3)alkoxy;

n is an integer from 2 to 4;
p is zero, 1 or 2;
q is zero or 1;
t is zero, 1 or 2;
u is zero, 1 or 2, that when Y is
is 2;
v is 1, 2 or 3;
Z is selected from the group consisting of: —NHSO2R17, —NHC(O)NR8R9, —NHC(O)OR8, —S(O)2NR8R9, substituted or unsubstituted cyclic carbamate; substituted or unsubstituted cyclic urea, cyclic imide and cyanoguanidine;

R8 and R9 are independently selected from H, substituted or unsubstituted (C1-C6)alkyl, substituted or unsubstituted (C3-C7) cycloalkyl and substituted or unsubstituted (C5-C14)aryl; and

R17 is chosen from phenyl and monocyclic heteroaryl, said phenyl and monocyclic heteroaryl optionally substituted with one or
two substituents chosen from OH, halogen, cyano, nitro, (C1-C3)alkylamino, (C1-C3)dialkylamino, (C1-C3)acylamino, (C1-C3)alkylsulfonyl, (C1-C3)alkylthio, (C1-C3)alkyl, (C1-C3)haloalkyl, (C1-C3)haloalkoxy, and (C1-C3)alkoxy.

US Pat. No. 10,159,724

CERAMIDE LEVELS IN THE TREATMENT AND PREVENTION OF INFECTIONS

Icahn School of Medicine ...

1. A method for treating pathogenic infections in a subject having Cystic Fibrosis, COPD, and/or an open wound, said method comprising:selecting a subject having Cystic Fibrosis, COPD, and/or an open wound and
administering to said selected subject a ceramidase under conditions effective to reduce ceramide in said selected subject.

US Pat. No. 10,119,143

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF THE ALAS1 GENE

ALNYLAM PHARMACEUTICALS, ...

1. A double-stranded ribonucleic acid (dsRNA) for inhibiting expression of ALAS1, wherein said dsRNA comprises a sense strand and an antisense strand, the antisense strand comprising a region of complementarity to an ALAS1 RNA transcript,wherein the sense strand comprises the sequence and all of the modifications of csasgaaaGfaGfuGfuCfuCfaucuuaL96 (SEQ ID NO: 4160), and wherein the antisense strand comprises the sequence and all of the modifications of usAfsAfGfaUfgAfgAfcAfcUfcUfuUfcUfgsgsu (SEQ ID NO: 4161),
wherein c, a, g, u=2?-OMe ribonucleosides; Af, Cf, Gf, Uf=2?F ribonucleosides; s=phosphorothioate, and
wherein

US Pat. No. 9,884,806

CYCLIC VINYLOGOUS AMIDES AS BROMODOMAIN INHIBITORS

ICAHN SCHOOL OF MEDICINE ...

1. A compound of formula 1
wherein:
U is (CH2)n, where n=1, 2 or 3;

R1 is selected from the group consisting of: (C1-C10)alkyl, substituted (C1-C10)alkyl, and nitrile;

Cy is a carbocycle or heterocycle;
R11and R12 are independently selected from the group consisting of: H, (C1-C10)alkyl, (C1-C10)perfluoroalkyl, halogen, nitrile, hydroxy, (C1-C10)alkoxy, perfluoro(C1-C10)alkoxy, (C1-C10)alkylthio, amino, (C1-C10)alkylamino, (C1-C10)acylamino, aryl, heteroaryl, aminocarbonyl, carboxyl, and (C1-C10)alkoxycarbonyl; or

taken together, R11 and R12 may form a 5, 6,or 7-membered carbocycle or heterocycle wherein said carbocycle or heterocycle may be optionally substituted
with R2;

R2 is selected from the group consisting of: halogen, (C1-C4)alkyl, halo(C1-C4)alkyl, hydroxy, (C1-C4)alkoxy, halo(C1-C4)alkoxy, carboxy, amino, (C1-C4)alkylamino and di(C1-C4)alkylamino;

Y is selected from

L and L? are independently a bond or (CR3R4)m where R3 and R4 are independently selected from the group consisting of H and (C1-C4)alkyl, and m is 1or 2;

R10 is chosen from carbocycle and heterocycle, wherein said carbocycle or heterocycle is optionally substituted with R7 and/or R8;

R20 is —C(?O)OR R21;

R21 is chosen from H and (C1-C4)alkyl;

R5 and R6 are independently selected from the group consisting of hydrogen, hydroxy, (C1-C10)hydrcarbyl, halo(C1-C10)hydrocarbyl, and (C1-C10)alkoxy;

R7 and R8 are independently selected from the group consisting of: hydroxy, halogen, (C1-C4)alkyl, halo(C1-C4)alkyl, hydroxy(C1-C4)alkyl, (C1-C4)alkoxy, halo(C1-C4)alkoxy, (C1-C4)alkylthio, (C1-C4)alkylcarbonyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, cyano, oxo, (C1-C4)alkylsulfonyl, amino, (C1-C4)alkylamino, di(C1-C4)alkylamino, (C1-C4)acylamino, aminocarbonyl, carboxyl, and (C1-C4)alkoxycarbonyl, where each said alkyl, aryl, heteroaryl, cycloalkyl, or heterocycloalkyl, may be further optionally substituted
with hydroxy, oxo, carboxy, carboxy(C1-C4)alkyl, hydroxy(C1-C4)alkyl, (C1-C4)alkoxy, (C1-C4)alkoxycarbonyl, (C1-C4)alkoxycarbonyl(C1-C4)alkyl, amino, (C1-C4)alkylamino, di(C1-C4)alkylamino, amido, (C1-C4)alkylamido, di (C1-C4)alkylamido, halogen, (C1-C4)alkyl, halo(C1-C4)alkyl, aryl, heteroaryl, heterocycloalkyl, or cycloalkyl;

or, taken together, R5 and R6, or R7 and R8 may form a 5, 6, or 7-membered carbocycle or heterocycle, wherein said carbocycle or heterocycle is optionally substituted
with R9;

R9 is selected from the group consisting of: halogen, (C1-C4)alkyl, halo(C1-C4)alkyl, hydroxy, (C1-C4)alkoxy, halo(C1-C4)alkoxy, amino, (C1-C4)alkylamino and di(C1-C4)alkylamino.

US Pat. No. 10,125,364

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF THE ALAS1 GENE

ALYNYLAM PHARMACEUTICALS,...

1. A double-stranded ribonucleic acid (dsRNA) for inhibiting expression of ALAS1, comprising:(i) an antisense strand that comprises the sequence of SEQ ID NO: 1296;
(ii) a sense strand comprising at least 15 contiguous nucleotides from SEQ ID NO: 1295; and
(iii) a duplex region of 15-30 base pairs in length.
US Pat. No. 10,087,443

COMPOSITIONS AND METHODS FOR MODULATING NEURONAL EXCITABILITY AND MOTOR BEHAVIOR

ICAHN SCHOOL OF MEDICINE ...

1. A method for treating or reducing the likelihood of the development or occurrence of seizures in an individual with Dravet Syndrome, comprising administering to said individual a therapeutically effective amount of microRNA-128 (miR-128) having the nucleotide sequence of SEQ ID NO: 1.

US Pat. No. 10,065,951

SMALL MOLECULE TRANSCRIPTION MODULATORS OF BROMODOMAINS

Icahn School of Medicine ...

10. A method for ameliorating one or more symptoms of and/or ameliorating the underlying metabolic causes of symptoms of a neurological disorder in a patient where NF-kB is implicated in the pathology of the disorder, the method comprising administering a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt form thereof, to the patient.
US Pat. No. 9,708,373

INFLUENZA VIRUS VACCINE AND USES THEREOF

Icahn School of Medicine ...

1. A polypeptide comprising:
a. an influenza hemagglutinin HA1 domain that comprises an HA1 N-terminal stem segment covalently linked to a linker of 1
to 50 heterologous residues that is in turn covalently linked to an HA1 C-terminal short stem segment; said HA1 domain in
tertiary or quaternary association with

b. an influenza hemagglutinin HA2 domain;
wherein the HA1 N-terminal stem segment consists of amino acid residues corresponding approximately to amino acids HA1N-term through Ap of an HA1 domain and the HA1 C-terminal short stem segment consists of amino acid residues corresponding approximately to
amino acids Bq through HA1C-term of an HA1 domain, wherein HA1N-term is the N-terminal amino acid of the HA1 domain, wherein HA1C-term is the C-terminal amino acid of the HA1 domain, wherein Ap is Cys that corresponds to amino acid position 52 of an HA1 using H3 numbering, wherein Bq is Cys that corresponds to amino acid position 305 of an HA1 using H3 numbering, and wherein the polypeptide lacks an influenza
virus hemagglutinin globular head domain.

US Pat. No. 9,968,670

INFLUENZA VIRUS VACCINES AND USES THEREOF

ICAHN SCHOOL OF MEDICINE ...

1. A method of immunizing a subject against an influenza virus comprising:(a) administering to the subject an effective amount of a first immunogenic composition comprising a first chimeric hemagglutinin (HA) polypeptide, wherein the first chimeric HA polypeptide comprises the stem domain of the HA from influenza virus A/Perth/16/2009 (H3N2) and the globular head domain of the HA from an influenza virus A/Duck/Czech/1956 (H4); and
(b) subsequent to the administration of the first immunogenic composition to the subject, administering to the subject a second immunogenic composition comprising a second chimeric hemagglutinin (HA) polypeptide, wherein the second chimeric HA polypeptide comprises an influenza virus hemagglutinin stem domain and an influenza virus hemagglutinin globular head domain, wherein the influenza virus hemagglutinin globular head domain is heterologous to the influenza virus hemagglutinin stem domain;
and wherein the globular head domain of the first chimeric influenza virus HA polypeptide is different than the globular head domain of the second chimeric HA polypeptide.

US Pat. No. 9,937,186

SULFONAMIDES DERIVED FROM TRICYCLYL-2-AMINOCYCLOALKANOLS AS ANTICANCER AGENTS

ICAHN SCHOOL OF MEDICINE ...

1. A compound of formula (I):
wherein:
B is selected from the group consisting of: direct bond, —O—, —(CH2—O)—, —(O—CH2)—, —C(?O)N(CH3)— and —N(CH3)C(?O)—;
A is selected from N and CH;
T is a benzene ring or a five or six membered heteroaromatic ring;
U is a benzene ring or a five or six membered heteroaromatic ring;
n is zero, 1 or 2;
R1, R2, R3 and R4 are chosen independently from H, OH, halogen, cyano, nitro, (C1-C3)alkylamino, (C1-C3)dialkylamino, (C1-C3)acylamino, (C1-C3)alkylsulfonyl, (C1-C3)alkylthio, (C1-C3)alkyl, (C1-C3)haloalkyl, (C1-C3)haloalkoxy, —CC(?O)O(C1-C3)alkyl, and (C1-C3)alkoxy;
R5 and R6 are chosen independently from H, halogen, cyano, nitro, azido, (C1-C3)haloalkyl, (C1-C3)haloalkoxy, and (C1-C3) haloalkylthio.

US Pat. No. 9,895,373

SUBSTITUTED PYRAZOLO[3,4-D]PYRIMIDINES AND USES THEREOF

The Regents of the Univer...

1. A method of treating cancer in a subject in need thereof, wherein said cancer is thyroid cancer, familial medullary thyroid
cancer, medullary thyroid carcinoma, pheochromocytoma, primary hyperparathyroidism, parathyroid hyperplasia, or papillary
thyroid cancer, said method comprising administering to the subject an effective amount of a compound having the formula:

wherein
R1 and R2 are independently hydrogen or substituted or unsubstituted alkyl;

R3 is independently substituted or unsubstituted alkyl;

R5 is independently halogen, —CN, —CXa3, —S(O)2H, —NO, —NO2, —C(O)H, —C(O)NH2, —S(O)2NH2, —OH, —SH, —SO2Cl, —SO3H, —SO4H, —NHNH2, —ONH2, —NHC?(O)NHNH2, —NHC?(O) NH2, —NHSO2H, —NHC?(O)H, —NHC(O)—OH, —NHOH, —OCF3, —OCHF2, —CO2H, or substituted or unsubstituted (C1- C6) alkyl;

R6 is independently halogen, —CN, —CX b3, —S(O)2H, —NO, —NO2, —C(O)H, —C(O)NH2, —S(O)2NH2, —OH, —SH, —SO2Cl, —SO3H, —SO4H, —NHNH2, —ONH2, —NHC?(O)NHNH2, —NHC?(O)NH2, —NHSO2H, —NHC?(O)H, —NHC(O)—OH, —NHOH, —OCF3, —OCHF2, or —CO2H;

L1 is independently a bond or substituted or unsubstituted alkylene;

z1 is independently an integer from 0 to 4;
z2 is independently an integer from 0 to 5; and
Xa and Xb are independently —F, —Cl, —Br, or—I; and

wherein treating cancer is amelioration of cancer disease, cancer injury, cancer pathology, or cancer condition.

US Pat. No. 9,822,418

MUTATIONS IN PDGFRB AND NOTCH3 AS CAUSES OF AUTOSOMAL DOMINANT INFANTILE MYOFIBROMATOSIS

ICAHN SCHOOL OF MEDICINE ...

1. A method of treating a subject having one or more missense mutations in PDGFRB and/or NOTCH, said method comprising:
providing an isolated biological sample from a subject;
contacting the sample with one or more reagents suitable for detecting the presence of one or more missense mutations in PDGFRB
and/or NOTCH3;

detecting, in the sample, the presence of the one or more mutations in PDGFRB and/or NOTCH3 based on said contacting; and
administering a therapy suitable for treatment of infantile myofibromatosis to a subject identified as having one or more
mutations in PDGFRB and/or NOTCH3.

US Pat. No. 9,815,847

PYRIMIDINE COMPOUNDS AS KINASE INHIBITORS

Icahn School of Medicine ...

1. A compound of formula (I):

or a salt thereof, wherein:
R1 is CN, S(O)jAr1, or S(O)k(C1-6 alkylene)Ar1;

j is 0, 1 or 2;
k is 0, 1 or 2;
each Ar1 is independently C6-10 aryl or 5-10 membered heteroaryl, each of which is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents independently
selected from Cy1, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, halo, C1-6 haloalkyl, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, C(?NRe1)NRc1Rd1, NRc1C(?NRe1)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1NRc1S(O)Rb1, NRc1S(O)2Rb1, NRc1S(O)2NRc1Rd1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1 and S(O)2NRc1Rd1;

each Cy1 is independently C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl or 4-10 membered heterocycloalkyl, each of which is unsubstituted or substituted by 1,
2, 3, 4 or 5 substituents independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, halo, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, C(?NRe1)NRc1Rd1, NRc1C(?NRe1)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, NRc1S(O)2NRc1Rd1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, S(O)2NRc1Rd1 and oxo;

A is NR2B;

R2A is C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ar2 or (C1-6 alkylene)Ar2;

R2B is H, C1-6 alkyl, C(O)C1-6 alkyl, Cy2A, C(O)Cy2A, (C1-6 alkylene)Cy2A and C(O)(C1-6 alkylene)Cy2A;

or R2A and R2B, together with the N atom to which they are attached, form a 5-, 6-, or 7-membered heterocycloalkyl group, which is unsubstituted
or substituted by 1, 2, 3, 4 or 5 substituents independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, halo, CN, NO2, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, C(?NRe2)NRc2Rd2, NRc2C(?NRe2)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2Rb2, NRc2S(O)2NRc2Rd2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, S(O)2NRc2Rd2 and oxo;

Ar2 is C6-10 aryl or 5-10 membered heteroaryl, each of which is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents independently
selected from Cy2B, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, halo, CN, NO2, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, C(?NRe2)NRc2Rd2, NRc2C(?NRe2)NRc2Rd2 NRc2Rd2, NRc2C(O)Rb2 NRc2C(O)ORa2 NRc2C(O)NRc2Rd2 NRc2S(O)Rb2, NRc2S(O)2Rb2, NRc2S(O)2NRc2Rd2S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2 and S(O)2NRc2Rd2;

Cy2A is C6-10 aryl, C3-7 cycloalkyl, 5-10 membered heteroaryl, or 5-10 heterocycloalkyl, each of which is unsubstituted or substituted by 1, 2, 3,
4 or 5 substituents independently selected from Cy2B, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, halo, CN, NO2, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, C(?NRe2)NRc2Rd2, NRc2C(?NRe2)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2Rb2, NRc2S(O)2NRc2Rd2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, S(O)2NRc2Rd2 and oxo;

each Cy2B is independently C6-10 aryl, C3-7 cycloalkyl, 5-10 membered heteroaryl, or 5-10 heterocycloalkyl, each of which is unsubstituted or substituted by 1, 2, 3,
4 or 5 substituents independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, halo, CN, NO2, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, C(?NRe2)NRc2Rd2, NRc2C(?NRe2)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2Rb2, NRc2S(O)2NRc2Rd2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, S(O)2NRc2Rd2 and oxo;

R3A is H, Cy3A1 or C1-6 alkyl, C2-6 alkenyl, C1-6 alkynyl, wherein said C1-6 alkyl forming R3A is optionally substituted with 1, 2, or 3 substituents independently selected from Cy3A2, halo, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, C(?NRd3)NRc3Rd3, NRc3C(?NRd3)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, NRc3S(O)Rb3, NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, S(O)2NRc3Rd3 and oxo;

R3B is H, Cy3B1 or C1-6 alkyl, C2-6 alkenyl, C1-6 alkynyl, wherein said C1-6 alkyl forming R3B is optionally substituted with 1, 2, or 3 substituents independently selected from Cy3B2, halo, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, C(?NRd3)NRc3Rd3, NRc3C(?NRd3)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, NRc3S(O)Rb3, NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, S(O)2NRc3Rd3 and oxo;

each Cy3A1, Cy3A2, Cy3B1 and Cy3B2 is, independently, C6-10 aryl, C3-7 cycloalkyl, 5-10 membered heteroaryl, or 5-10 heterocycloalkyl, each of which is unsubstituted or substituted by 1, 2, 3,
4 or 5 substituents independently selected from RCy3, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, halo, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, C(?NRe3)NRc3Rd3, NRc3C(?NRe3)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, NRc3S(O)Rb3, NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, S(O)2NRc3Rd3 and oxo;

or R3A and R3B, together with the N atom to which they are attached, form a 5-, 6-, or 7-membered heterocycloalkyl group, which is unsubstituted
or substituted by 3, 4 or 5 substituents independently selected from RCy3, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, halo, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, C(?NRe3)NRc3Rd3, NRc3C(?NRe3)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, NRc3S(O)Rb3, NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, S(O)2NRc3Rd3 and oxo;

each RCy3 is independently selected from C6-10 aryl, C3-7 cycloalkyl, 5-10 membered heteroaryl, 5-10 heterocycloalkyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, halo, C1-6 haloalkyl, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, C(?NRe3)NRc3Rd3, NRc3C(?NRe3)NRc3Rd3 NRc3Rd3 NRc3C(O)Rb3 NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, NRc3S(O)Rb3, NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, S(O)2NRc3Rd3 and oxo; wherein each of said C6-10 aryl, C3-7 cycloalkyl, 5-10 membered heteroaryl and 5-10 heterocycloalkyl forming RCy3 is independently unsubstituted or substituted by 1, 2, or 3 substituents independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, halo, C1-6 haloalkyl, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, C(?NRe3)NRc3Rd3, NRc3C(?NRe3)NRc3Rd3, NRc3Rd3 NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, NRc3S(O)Rb3, NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, S(O)2NRc3Rd3 and oxo;

each Ra1, Rb1, Rc1, Rd1, Ra2, Rb2, Rc2, Rd2, Ra3, Rb3, Rc3 and Rd3 is independently selected from H, C1-6 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-10 cycloalkyl-C1-4 alkyl, (5-10 membered heteroaryl)-C1-4 alkyl or (4-10 membered heterocycloalkyl)-C1-4 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-10 cycloalkyl-C1-4 alkyl, (5-10 membered heteroaryl)-C1-4 alkyl and (4-10 membered heterocycloalkyl)-C1-4 alkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from C1-4 alkyl, C1-4 haloalkyl, halo, CN, ORa4, SRa4, C(O)Rb4, C(O)NRc4Rd4, C(O)ORa4, OC(O)Rb4, OC(O)NRc4Rd4, NRc4Rd4, NRc4C(O)Rb4, NRc4C(O)NRc4Rd4, NRc4C(O)ORa4, C(?NRe4)NRc4Rd4, NRc4C(?NRe4)NRc4Rd4, S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4, NRc4S(O)2Rb4, NRc4S(O)2NRc4Rd4 and S(O)2NRc4Rd4;

or any Rc1 and Rd1 attached to the same N atom, any Rc2 and Rd2 attached to the same N atom, any Rc3 and Rd3 attached to the same N atom, or any Rc4 and Rd4 attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl
group optionally substituted with 1, 2 or 3 substituents independently selected from C1-6 alkyl, C3-7 cycloalkyl, 3-7 membered heterocycloalkyl, C6-10 aryl, 5-6 membered heteroaryl, C1-6 haloalkyl, halo, CN, ORa4, SRa4, C(O)Rb4, C(O)NRc4Rd4, C(O)ORa4, OC(O)Rb4, OC(O)NRc4Rd4, NRc4Rd4 NRc4C(O)Rb4 NRc4C(O)NRc4Rd4 NRc4C(O)ORa4, C(?NRe4)NRc4Rd4, NRc4C(?NRe4)NRc4Rd4, S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4, NRc4S(O)2Rb4, NRc4S(O)2NRc4Rd4 and S(O)2NRc4Rd4;

each Ra4, Rb4, Rc4 and Rd4 is independently selected from H, C1-4 alkyl, C1-4 haloalkyl, C2-4 alkenyl and C2-4 alkynyl, wherein said C1-4 alkyl, C2-4 alkenyl, and C2-4 alkynyl, is optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C1-4 alkyl, C1-4 alkoxy, C1-4 alkylthio, C1-4 alkylamino, di(C1-4 alkyl)amino, C1-4 haloalkyl, and C1-4 haloalkoxy;

or any Rc4 and Rd4 attached to the same N atom, together with the N atom to which they are attached, form a 3-, 4-, 5-, 6-, or 7-membered heterocycloalkyl
group optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C1-6 alkyl, C1-4 alkoxy, C1-4 alkylthio, C1-4 alkylamino, di(C1-4 alkyl)amino, C1-4 haloalkyl and C1-4 haloalkoxy; and

each Re1, Re2, Re3 and Re4 is independently selected from H, C1-4 alkyl and CN;

with the proviso that the compound is other than
3-(4-ethylamino-2-phenylamino-pyrimidin-5-yl)acrylonitrile and salts thereof.
US Pat. No. 9,816,985

METHOD FOR PREDICTING RISK OF EXPOSURE TO INTERSTITIAL FIBROSIS AND TUBULAR ATROPHY WITH CLUSTERIN

Icahn School of Medicine ...

1. A method for treating a kidney transplant recipient at an increased risk of developing interstitial fibrosis or tubular
atrophy which comprises:
obtaining a post-transplant urine sample from the kidney transplant recipient;
measuring the level of clusterin in the urine sample;
comparing the level of clusterin in the patient sample to the level of clusterin in a control sample from the urine of a non-fibrotic
kidney transplant recipient;

diagnosing a kidney transplant recipient with a clusterin level that is significantly higher than the clusterin level in the
control as being at an increased risk of developing interstitial fibrosis or tubular atrophy and

treating the recipient for interstitial fibrosis or tubular atrophy.
US Pat. No. 10,188,705

DOSE ESCALATION ENZYME REPLACEMENT THERAPY FOR TREATING ACID SPHINGOMYELINASE DEFICIENCY

Icahn School of Medicine ...

1. A method for treating an acid sphingomyelinase deficiency (ASMD), comprising:a. administering to a human subject in need thereof one or more initial doses of 0.1 mg/kg recombinant human acid sphingomyelinase (rhASM); and
b. administering sequentially escalating higher doses of rhASM to the human subject if the subject does not manifest one or more moderate or severe adverse events, wherein the higher doses are from 0.1 mg/kg to 1.0 mg/kg higher than the previous dose.
US Pat. No. 9,994,898

MATERIALS AND METHODS FOR IDENTIFYING SPINAL MUSCULAR ATROPHY CARRIERS

Icahn School of Medicine ...

8. A method of identifying a subject with an increased risk of SNM1 duplication and an increased risk of being a carrier of Spinal Muscular Atrophy (SMA) comprising:(a) obtaining a DNA sample from the subject;
(b) analyzing the DNA sample using multiplex ligation-dependent probe amplification (MLPA) to determine the SMN1 copy number in the subject;
(c) analyzing the DNA to detect the alleles present at each of D5S681, D5S435, MS1 and D5S610;
(d) detecting in the DNA sample the presence of a haplotype selected from the group consisting of
(i) a haplotype comprising D5S681 having allele 2, D5S435 having allele 5, MS1 having allele 4, and D5S610 having allele 5;
(ii) a haplotype comprising D5S681 having allele 2, D5S435 having allele 5, MS1 having allele 9, and D5S610 having allele 4;
(iii) a haplotype comprising D5S681 having allele 2, D5S435 having allele 5, and MS1 having allele 6; and
(iv) a haplotype comprising D5S681 having allele 2, D5S435 having allele 5, MS1 having allele 6, and D5S610 having allele 10;
wherein the presence of two copies of SMN1 and the presence of the haplotype identifies the subject as having an increased risk of SMN1 duplication and an increased risk of being a carrier of SMA.
US Pat. No. 9,937,246

THERAPEUTIC ACID CERAMIDASE COMPOSITIONS AND METHODS OF MAKING AND USING THEM

Icahn School of Medicine ...

1. A therapeutic composition comprising a ceramidase mixture comprising:a recombinant inactive acid ceramidase precursor and
a recombinant active acid ceramidase; and
a pharmaceutically acceptable carrier;
wherein the amount of said inactive acid ceramidase precursor is greater than the amount of said active ceramidase in said ceramidase mixture, and wherein said therapeutic composition has no detectable acid sphingomyelinase activity.

US Pat. No. 9,868,730

KAPPA OPIOID RECEPTOR SELECTIVE COMPOUNDS, COMPOSITIONS, AND USES THEREOF

The Trustees of Columbia ...

1. A compound of formula I:

wherein
X1 is N;

n is an integer between 1 and 10;
HET is a heteroaromatic ring; and
R is a —C1-4alkylhalo; or

crystalline forms, hydrates, or salts thereof.
US Pat. No. 9,868,946

METHOD OF ISOLATING PURE MITOCHONDRIAL DNA

Icahn School of Medicine ...

1. A method for preparing circular double stranded DNA substantially free of linear genomic DNA (gDNA) comprising the steps
of:
a) forming a cellular lysate by lysing mammalian cells containing linear genomic DNA of length greater than a billion base
pairs and circular double stranded DNA of length less than 30,000 base pairs;

b) incubating said lysate with an amount of Proteinase K effective to digest proteins in said lysate;
c) digesting any RNA in said lysate;
d) adding a Protein Precipitation reagent to said lysate to obtain a precipitate and a supernatant;
e) precipitating total DNA in said supernatant and forming a pellet;
f) suspending the supernatant pellet in a buffer;
g) incubating the suspended pellet at about 70° C. for about 30 minutes to form a solution;
h) incubating the solution containing the pellet with an amount of an Exonuclease, selected from the group consisting of Hind
Exonuclease V, T5 exonuclease, and Exonuclease V for a time and at a concentration effective to cleave linear genomic DNA
and obtain circular double stranded DNA;

i) incubating said circular double stranded DNA with an amount of carboxylated solid phase reversible immobilization magnetic
beads effective to bind to said circular double stranded DNA; and

j) washing said beads with ethanol and eluting said circular double stranded DNA from said pellet,
wherein the method is free of ultra-centrifugation and provides circular double stranded DNA from mammalian cells that is
at least 90% free of linear genomic DNA.

US Pat. No. 10,119,109

AUTOMATED, MULTIFUNCTIONAL, ENGINEERED CARDIAC TISSUE CULTURE AND TESTING BIOREACTOR SYSTEM

ICAHN SCHOOL OF MEDICINE ...

1. A bioreactor system that is configured to provide length control of engineered tissue and to measure one or more properties of the engineered tissue comprising:a housing that includes a culture well;
at least one first flexible post suspended in the culture well;
at least one second rigid post suspended in the culture well, the second post being spaced from the first post such that the engineered tissue is grown therebetween;
a first device for measuring a contractile force of the engineered tissue, the device including the at least one first post which comprises a fiber-optic that is operatively coupled to a light source and configured to flex when the engineered tissue contracts, the first device further including a sensor for detecting a degree of movement of the at least one first post; and
a second device for controlling the length of the engineered tissue, the second device including the at least one rigid second post and an actuator that is operatively coupled to the at least one second post for moving the at least one second post in a controlled manner within the culture well so as to cause a change in a distance between the at least one first post and the at least one second post and thereby control the length of the engineered tissue;
wherein the housing includes a base which contains the culture well and a removable lid with the second device being fixedly attached to the lid;
wherein the fiber-optic passes through the lid with an upper end of the fiber-optic proximate the lid representing a more rigid section of the first post, with a lower section thereof representing a flexible section that flexes in response to applied forces due to tissue contractions.

US Pat. No. 9,952,195

METHOD OF FORMING A LIPID BILAYER

Icahn School of Medicine ...

1. A process for forming a droplet interface bilayer (DIB) comprising the steps of:providing a housing wherein the housing includes at least one aperture that comprises a cis portion and a trans portion, at least one cis electrode receptacle and at least one trans electrode receptacle, wherein the cis electrode receptacle is operatively connected to the cis portion, and the trans electrode receptacle is operatively connected to the trans portion, and the number of cis and trans electrode receptacles equals the number of cis and trans portions;
treating at least one ground electrode and one voltage electrode with a buffer;
inserting a treated electrode into each of the cis and trans electrode receptacles;
placing the housing into a holder;
securing the holder with the housing into a container;
introducing an oil/lipid phase into the container, wherein the oil/lipid phase enters the aperture of the housing;
delivering at least two aqueous droplets to the oil/lipid phase in such a manner that at least one aqueous droplet is disposed within the cis portion of the aperture and at least one aqueous droplet is disposed within the trans portion of the aperture; and
removing a portion of the oil/lipid phase from the container, wherein a portion of the oil/lipid phase in the aperture is removed, thereby lowering a level of the oil/lipid phase in the cis and trans portions of the aperture which results in the aqueous droplets in the cis and trans portions spontaneously re-organizing and moving closer to one another until the aqueous droplets contact one another thereby forming the lipid bilayer at the location at which the aqueous droplets contact one another.

US Pat. No. 9,937,180

CONSTRAINED TRICYCLIC SULFONAMIDES

ICAHN SCHOOL OF MEDICINE ...

1. A compound of formula (I):
wherein:
B is selected from the group consisting of: —S—, —(CH2—CH2)—, and —CH?CH—;
A is selected from N and CH;
n is zero, 1 or 2;
X1 is selected from —H, —F, —Cl, —CF3, and —CN;
X2 is selected from —H, —F, —Cl, —CF3, and —CN; and
Y represents one or two substituents each independently selected from —H, —F, —Cl, —(C1-C3)haloalkyl, —(C1-C3)haloalkoxy, —(C1-C3)alkoxy, —C(?O)(C1-C3)alkyl, —C(?O)H, —(C1-C3)hydroxyalkyl, —(C1-C3)haloalkylthio, —N3, and —CN.
US Pat. No. 9,701,723

VACCINES FOR USE IN THE PROPHYLAXIS AND TREATMENT OF INFLUENZA VIRUS DISEASE

Icahn School of Medicine ...

1. An immunogenic composition capable of inducing antibodies that are cross-reactive among influenza hemagglutinin (HA) subtypes,
the immunogenic composition comprising a flu polypeptide comprising an immunogenic core polypeptide, wherein the immunogenic
core polypeptide is (a) directly or indirectly linked at its N- and/or C-terminus to one or more tags; (b) directly or indirectly
linked at its N- and/or C-terminus to a T cell epitope; (c) directly or indirectly linked at its N- and/or C-terminus to a
Toll Like Receptor ligand; or (d) directly or indirectly linked at its N- and/or C-terminus to a T4 foldon domain or a fragment
thereof, wherein the immunogenic core polypeptide is less than 75 amino acids in length, and wherein the immunogenic core
polypeptide comprises:
R-I-Q-D-L-E-K-Y-V-E-D-T-K-I-D-L-W-S-Y-N-A-E-L-L-V-A-L-E-N-Q-H-T-I-D-L-T-D-S-E-M-N-K-L-F-E-X1T-X2-X3-Q-L-R-E-N-A (SEQ ID NO: 15), wherein X1, X2, and X3 are hydrophilic, basic amino acids.

US Pat. No. 10,251,922

NEWCASTLE DISEASE VIRUSES AND USES THEREOF

Icahn School of Medicine ...

1. A method for treating cancer, comprising administering to a human subject in need thereof a chimeric New Castle Disease Virus (NDV) and an antagonist of an inhibitory receptor of an immune cell, wherein the chimeric NDV comprises a packaged genome comprising a nucleotide sequence encoding a cytokine, wherein the cytokine is expressed by the NDV, wherein the cytokine is IL-12, wherein the inhibitory receptor is PD1, and wherein the antagonist is an antibody that specifically binds to the inhibitory receptor.

US Pat. No. 10,239,830

BENZENESULFONAMIDE UPREGULATORS OF NPC1 FOR NEIMANN-PICK DISEASE AND OTHER LYSOSOMAL STORAGE DISORDERS

ICAHN SCHOOL OF MEDICINE ...

1. A method of treating a lysosomal storage disorder comprising administering a compound of formula IwhereinR1 is selected from hydrogen and (C1-C6)alkyl;
R2 is selected from (C1-C6)alkyl, optionally substituted benzyl, meta-substituted phenyl and para-substituted phenyl, wherein substituents on the benzyl or phenyl are selected from (C1-C6)alkyl, halogen, halo(C1-C6)alkyl, (C1-C6)alkoxy, and cyano; or
R1 and R2, together with the nitrogen to which they are attached, form an optionally substituted and/or fused heterocycle;
R3, R4, R5 and R6 are independently selected from hydrogen, (C1-C6)alkyl, halogen, hydroxy, cyano, nitro, amino, halo(C1-C6)alkyl, (C1-C6)alkoxy, and (C1-C6)alkoxy substituted with an amine or saturated nitrogen heterocycle;
Cy is chosen from adamantyl, optionally substituted monocyclic aryl, and optionally substituted monocyclic heteroaryl, with the proviso that when R2 is (C1-C6)alkyl, Cy is not unsubstituted aryl or heteroaryl.
US Pat. No. 10,167,510

NUCLEIC ACIDS, METHODS AND KITS FOR THE DIAGNOSIS OF DYT6 PRIMARY TORSION DYSTONIA

Icahn School of Medicine ...

1. An isolated nucleic acid comprising the sequence of SEQ ID NO: 50 or SEQ ID NO: 51, or the complementary sequence of SEQ ID NO: 50 or 51; wherein the nucleic acid is labeled with a moiety selected from the group consisting of radioisotopes, fluorescent compounds, enzymes, and enzyme co-factors.

US Pat. No. 10,123,737

SYSTEMS AND METHODS FOR TREATING A PSYCHIATRIC DISORDER

ICAHN SCHOOL OF MEDICINE ...

1. A computing system, comprising:one or more processors;
memory; and
one or more programs, wherein the one or more programs are stored in the memory and are configured to be executed by the one or more processors to treat a subject in need of treatment of a psychiatric disorder, the one or more programs including instructions for:
conducting a therapy session, the therapy session comprising:
i) sequentially displaying each respective expression image in a plurality of expression images for a predetermined amount of time, the plurality of expression images comprising a plurality of subsets of expression images, wherein each expression image in the plurality of expression images is (a) independently associated with a respective expression in a set of expressions, (b) engineered to display or exhibits a predetermined intensity of the respective expression on an intensity scale that ranges from low intensity to high intensity of the respective expression and (c) configured to induce human amygdala activation,
ii) responsive to completion of each respective expression image subset within the plurality of expression images, receiving a response from the subject to a query as to whether the first and the last expression image in the respective expression image subset exhibits the same emotion, and wherein each respective expression image subset within the plurality of expression images consists of N expression images, wherein N is a predetermined integer,
iii) determining a score for each respective expression image subset within the plurality of expression images based at least in part upon the response to the query for the respective expression image subset, and
iv) resetting the value of N to a new positive integer value based at least in part on the plurality of scores, wherein
the predetermined intensity of the respective expression on the intensity scale of respective images of a first subset of expression images in the plurality of expression images is greater than or less than the predetermined intensity of the respective expression on the intensity scale of respective images in the plurality of expression images of a second subset of expression images in the therapy session, wherein the second subset is displayed after the first subset.
US Pat. No. 10,098,945

GENETICALLY ENGINEERED SWINE INFLUENZA VIRUS AND USES THEREOF

Icahn School of Medicine ...

1. A method for preventing swine influenza virus disease in a pig, comprising administering to the pig an effective amount of an immunogenic composition comprising a genetically engineered attenuated swine influenza virus having an impaired interferon antagonist phenotype, wherein the virus comprises a swine influenza virus NS1 gene with a mutation resulting in a swine influenza virus NS1 protein having a deletion of between 90 and 94 amino acid residues from the carboxy-terminus of NS1.
US Pat. No. 10,238,721

THERAPEUTIC ACID CERAMIDASE COMPOSITIONS AND METHODS OF MAKING AND USING THEM

ICAHN SCHOOL OF MEDICINE ...

1. A composition comprising a ceramidase mixture comprising:an inactive acid ceramidase precursor;
an active acid ceramidase; and
a pharmaceutically acceptable carrier,wherein the composition has no detectable acid sphingomyelinase activity.
US Pat. No. 10,137,189

INFLUENZA VIRUS VACCINES AND USES THEREOF

Icahn School of Medicine ...

1. A method of immunizing a subject against an influenza virus comprising:(a) administering to the subject an effective amount of a first immunogenic composition comprising a first chimeric hemagglutinin (HA) polypeptide, wherein the first chimeric HA polypeptide comprises an influenza virus hemagglutinin stem domain and an influenza virus hemagglutinin globular head domain, wherein the influenza virus hemagglutinin globular head domain is heterologous to the influenza virus hemagglutinin stem domain; and
(b) subsequent to the administration of the first immunogenic composition to the subject, administering to the subject an effective amount of a second immunogenic composition comprising a second chimeric hemagglutinin (HA) polypeptide, wherein the second chimeric HA polypeptide comprises the stem domain of the HA from influenza virus A/California/4/2009 (H1N1) and the globular head domain of the HA from an influenza virus A/Vietnam/1203/2004 (H5), A/Indonesia/5/2005 (H5), A/Anhui/1/2005 (H5), A/Bar headed loose/Quinghai/1A/2005(H5), A/turkey/Turkey/1/2005 (H5), or A/whooperswan/Mongolia/244/2005 (H5),
and wherein the globular head domain of the first chimeric influenza virus HA polypeptide is different than the globular head domain of the second chimeric HA polypeptide.
US Pat. No. 10,105,422

SUMOYLATION OF SERCA2A AND CARDIOVASCULAR DISEASE

Icahn School of Medicine ...

1. A method of treating a cardiac dysfunction in a subject comprising administering a recombinant adeno-associated virus vector comprising an expressible coding region encoding a SUMO1 protein, wherein the coding region is operably linked to at least one expression control element, in a therapeutically effective amount to treat the cardiovascular dysfunction in the subject, wherein the cardiac dysfunction is selected from the group consisting of heart failure, pressure overload-induced cardiac dysfunction, and cardiac dysfunction induced by inhibited calcium decay.
US Pat. No. 10,436,789

HCV CORE AND MINICORE BINDING MOLECULES

Icahn School of Medicine ...

1. A hepatitis C virus (HCV) core protein-binding molecule, comprising:a) a light chain variable region comprising
i) a first light chain complementarity determining region (CDRL1) consisting of an amino acid sequence selected from the group consisting of SEQ ID NO: 2, and SEQ ID NO: 2 with one or more conservative amino acid changes;
ii) a second light chain CDR (CDRL2) consisting of an amino acid sequence selected from the group consisting of SEQ ID NO:3 and SEQ ID NO:3 with one or more conservative amino acid changes; and
iii) a third light chain CDR (CDRL3) consisting of an amino acid sequence selected from the group consisting of SEQ ID NO:4 and SEQ ID NO:4 with one or more conservative amino acid changes; and
b) a heavy chain variable region, comprising
i) a first heavy chain CDR (CDRH1) consisting of an amino acid sequence selected from the group consisting of SEQ ID NO:6 and SEQ ID NO:6 with one or more conservative amino acid changes;
ii) a second heavy chain CDR (CDRH2) consisting of an amino acid sequence selected from the group consisting of SEQ ID NO:7 and SEQ ID NO:7 with one or more conservative amino acid changes; and
iii) a third heavy chain CDR (CDRH3) consisting of an amino acid sequence selected from the group consisting of SEQ ID NO:8 and SEQ ID NO:8 with one or more conservative amino acid changes.
US Pat. No. 10,400,239

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF THE ALAS1 GENE

ALNYLAM PHARMACEUTICALS, ...

1. A double-stranded ribonucleic acid (dsRNA) for inhibiting expression of ALAS1, wherein said dsRNA comprises a sense strand and an antisense strand each of which is 15-30 nucleotides in length, the antisense strand comprising a region of complementarity to an ALAS1 RNA transcript, wherein the antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from SEQ ID NO: 3686, SEQ ID NO: 3688, or SEQ ID NO: 3690, and wherein the region of complementarity is 19 to 24 nucleotides in length.
US Pat. No. 10,308,985

METHODS FOR DIAGNOSING RISK OF RENAL ALLOGRAFT FIBROSIS AND REJECTION

Icahn School of Medicine ...

1. A method for diagnosing and treating a renal allograft recipient at risk for developing fibrosis of the allograft and allograft loss, the method comprising:(a) determining the expression levels of said microRNAs in a blood sample using Nanostring analysis, wherein the microRNAs are hsa-mir-128, hsa-mir-29b-3p, hsa-mir-302b-3p, and hsa-mir-192-5p;
(b) determining the expression levels of said microRNAs in a control sample using Nanostring analysis for each microRNA;
(c) diagnosing the recipient as being at risk for developing fibrosis of the allograft and allograft loss if the expression levels of said miRNA samples are altered relative to a control level for each microRNA, and
(d) treating the allograft recipient by administering an effective amount of a drug for treating fibrosis of the allograft and allograft loss.
US Pat. No. 10,308,913

CHIMERIC VIRUSES PRESENTING NON-NATIVE SURFACE PROTEINS AND USES THEREOF

Icahn School of Medicine ...

1. A chimeric Newcastle Disease Virus (NDV), comprising a packaged genome comprising a nucleotide sequence encoding an F-fusion protein, wherein the F-fusion protein comprises the transmembrane and cytoplasmic domains of an NDV F protein and an ectodomain of a heterologous protein that is anchored by the C-terminus of the heterologous protein, so that the F-fusion protein is expressed and incorporated into the chimeric NDV, and wherein the heterologous protein is not a paramyxovirus antigen.

US Pat. No. 10,247,797

METHODS FOR PRODUCING A SEMI-ADIABATIC SPECTRAL-SPATIAL SPECTROSCOPIC IMAGING SEQUENCE AND DEVICES THEREOF

ICAHN SCHOOL OF MEDICINE ...

1. A method for generating a magnetic resonance image based on a semi-adiabatic spectral-spatial spectroscopic imaging sequence, the method comprising:generating, by a magnetic resonance imaging computing device, a pulse control signal comprising a pair of adiabatic pulses and a linear phase pulse;
transforming, by the magnetic resonance imaging computing device, the pulse control signal into a pair of spectrally and spatially selective refocusing pulses having a spectral bandwidth of at least 500 Hz and an excitation pulse;
outputting, by the magnetic resonance imaging computing device, the pair of spectrally and spatially selective refocusing pulses and the excitation pulse to a waveform generator to produce the semi-adiabatic spectral-spatial spectroscopic imaging sequence; and
generating, by the magnetic resonance imaging computing device, a magnetic resonance image based on the pair of spectrally and spatially selective refocusing pulses, the excitation pulse, and alternating lobed gradient pulses.
US Pat. No. 10,238,723

AUTOLOGOUS TUMOR LYSATE-LOADED DENDRITIC CELL VACCINE FOR TREATMENT OF LIVER CANCER

Icahn School of Medicine ...

1. An immunogenic composition consisting of dendritic cells (DCs) (i) autologous to a subject with a liver tumor, (ii) matured in the presence of lipopolysaccharide as the only maturation agent, (iii) loaded with hepatocellular (HCC) tumor cell lysate prepared by performing repeated freeze-thaw cycles of liver tumor cells obtained from the subject, and (iv) a pharmaceutically acceptable carrier or excipient; andwherein the DCs selectively reduce T regulatory cells (Tregs) in the liver tumor when administered to the subject.
US Pat. No. 10,444,242

DETECTION METHODS EMPLOYING HCV CORE LIPID AND DNA BINDING DOMAIN MONOCLONAL ANTIBODIES

ABBOTT LABORATORIES, Abb...

1. A method for the detection of HCV protein in a test sample comprising:(i) contacting a test sample suspected of containing HCV with a first antibody, or antigen-binding portion thereof, which comprises heavy chain CDR1, CDR2, and CDR3 amino acid sequences of SEQ ID NO: 588, SEQ ID NO: 589, and SEQ ID NO: 590, respectively, and light chain CDR1, CDR2, and CDR3 amino acid sequences of SEQ ID NO: 585, SEQ ID NO: 586, and SEQ ID NO: 587, respectively, to form a complex between said first antibody, or said antigen-binding portion thereof, and said HCV core protein located within said test sample;
(ii) contacting said complex formed in step (i) with a second antibody, or antigen-binding portion thereof, which specifically binds to the amino acid sequence of SEQ ID NO: 574 in the lipid binding domain of HCV core protein, to form a complex between said second antibody, or said antigen-binding portion thereof, and said complex formed in step (i);
and
(iii) detecting said complex formed in step (ii).

US Pat. No. 10,429,473

METHODS FOR PRODUCING A SLICE-SELECTIVE ADIABATIC T2 PREPARATION PULSE AND DEVICES THEREOF

Icahn School of Medicine ...

1. A method for generating a magnetic resonance image based on a slice-selective adiabatic magnetization T2 preparation pulse, the method comprising:generating, by a magnetic resonance imaging computing device, a pulse control signal comprising an adiabatic half passage pulse control signal, an adiabatic full passage pulse control signal, and a reverse adiabatic half passage pulse control signal;
generating, by the magnetic resonance imaging computing device, a plurality of slice-selective linear phase subpulse control signals;
sampling, by the magnetic resonance imaging computing device, the pulse control signal using the plurality of slice-selective linear phase subpulse control signals to generate a slice-selective adiabatic T2 preparation control signal;
generating, by the magnetic resonance imaging computing device, an alternating polarity gradient pulse control signal for the slice-selective adiabatic T2 preparation pulse;
outputting, by the magnetic resonance imaging computing device, the slice-selective adiabatic T2 preparation control signal to a waveform generator to produce the slice-selective adiabatic T2 preparation pulse;
outputting, by the magnetic resonance image computing device, an image sequence based on the slice-selective adiabatic T2 preparation pulse and the alternating polarity gradient pulse control signal; and
generating, by the magnetic resonance imaging computing device, a magnetic resonance image based on the image sequence.
US Pat. No. 10,428,308

MESODERM AND DEFINITIVE ENDODERM CELL POPULATIONS

Icahn School of Medicine ...

1. A method of making a cell population enriched for endoderm cells comprising culturing pluripotent stem cells in the presence of activin or nodal, and Wnt, for a time sufficient to provide brach+/HNF3?+ cells, and culturing said brach+/HNF3?+ cells in the presence of activin and an inhibitor of Wnt signalling for a time sufficient to provide a cell population enriched for endoderm cells.
US Pat. No. 10,392,600

METHOD OF GENERATING HUMAN PANCREATIC CELLS

ICAHN School of Medicine ...

1. A method for generating human pancreatic cells comprising the steps of:i) culturing human embryoid bodies in the presence of a concentration of 100 ng/ml of activin such that a cell population enriched for endoderm is obtained; and ii) differentiating the cell population enriched for endoderm obtained in step i) under conditions such that human pancreatic cells are generated.

US Pat. No. 10,267,880

METHODS FOR PRODUCING A PULSE-PAIR FOR MAGNETIC RESONANCE IMAGING AND DEVICES THEREOF

Icahn School of Medicine ...

1. A method for generating a magnetic resonance image, the method comprising:generating, by a magnetic resonance imaging computing device, a pulse pair control signal comprising an adiabatic pulse and a matched phase non-adiabatic pulse;
transforming, by the magnetic resonance imaging computing device, the pulse pair control signal into a power independent of number of slices pulse pair control signal comprising a power independent of number of slices adiabatic pulse and a power independent of number of slices matched phase non-adiabatic pulse;
outputting, by the magnetic resonance imaging computing device, the power independent of number of slices pulse pair control signal to a waveform generator to produce the power independent of number of slices pulse pair in a spin echo sequence; and
generating, by the magnetic resonance imaging computing device, a magnetic resonance image based on the power independent of number of slices pulse pair.

US Pat. No. 10,450,282

STEREOSPECIFIC PROCESS FOR 3-HETEROCYCLYLCYCLOALIPHATIC-1,2-DIOLS

ICAHN SCHOOL OF MEDICINE ...

1. A process for preparing a substantially enantiomerically pure compound of formula (I):
wherein:
A is selected from the group consisting of a direct bond, —SO2—, and —C(?O)—;
B is selected from the group consisting of a direct bond, —O—, —SO— and —SO2—;
T is a benzene ring or a five or six membered heteroaromatic ring;
U is a benzene ring or a five or six membered heteroaromatic ring; and
R1, R2, R3 and R4 are chosen independently from H, OH, halogen, cyano, nitro, (C1-C3)alkylamino, (C1-C3)dialkylamino, (C1-C3)acylamino, (C1-C3)alkylsulfonyl, (C1-C3)alkylthio, (C1-C3)alkyl, (C1-C3)haloalkyl, (C1-C3)haloalkoxy, (C1-C3)haloalkylthio, —CC(?O)O(C1-C3)alkyl, and (C1-C3)alkoxy;
Q is chosen from direct bond, —CH2—, —CH2CH2—, —O—, —CH(OH)—, —CH(COOR5)—, —CH(CONR?R?)—, —CH(CH2)NR?R?, —CH(CN)—, —S(O)n—, —CH(NHBoc), —CH(NHCBZ), —NR6—,

R5 is H or (C1-C4)alkyl;
R6 is chosen from (C1-C4)alkyl, (C1-C4)acyl, (C4-C7)alkoxycarbonyl, and benzyloxycarbonyl;
R? and R? are independently chosen from H, lower alkyl, substituted alkyl, aryl, substituted aryl; or R? and R? together with the nitrogen to which they are attached, may form an optionally substituted heterocyclic ring;
said process comprising:
(a) reacting a compound of formula II
with a compound of formula IIIwherein R7 is (C1-C4)alkyl,in the presence of a chiral palladium catalyst to provide a product of formula IV
and(b) oxidizing said product of formula IV with osmium tetroxide to provide I.
US Pat. No. 10,450,375

METHODS OF TREATING SICKLE CELL DISEASE

Icahn School of Medicine ...

1. A method of treating a sickle cell disease subject in vaso-occlusive crisis comprising administering an E-selectin inhibitor that interacts with a calcium-binding lectin domain of E-selectin in an amount effective to treat the subject.
US Pat. No. 10,350,277

CERAMIDASE AND CELL DIFFERENTIATION

Icahn School of Medicine ...

1. An in vitro method of producing chondrocytes, said method comprising:selecting a population of mammalian cells having the potential to differentiate into chondrocytes, and
treating the selected cell population with a ceramidase in a differentiation medium capable of stimulating differentiation into chondrocytes to transform one or more of the cells in the selected population into chondrocytes in increased number as compared to the differentiation medium alone.

US Pat. No. 10,351,511

CYCLIC VINYLOGOUS AMIDES AS BROMODOMAIN INHIBITORS

ICAHN SCHOOL OF MEDICINE ...

1. A method for treating a disease or disorder arising from inappropriate activity of proteins containing an acetyl-lysine residue, said method comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula I
wherein:
U is (CH2)n, where n=1, 2 or 3;
R1 is selected from the group consisting of: (C1-C10)alkyl, substituted (C1-C10)alkyl, and nitrile;
Cy is a carbocycle or heterocycle;
R11 and R12 are independently selected from the group consisting of: H, (C1-C10)alkyl, (C1-C10)perfluoroalkyl, halogen, nitrile, hydroxy, (C1-C10)alkoxy, perfluoro(C1-C10)alkoxy, (C1-C10)alkylthio, amino, (C1-C10)alkylamino, (C1-C10)acylamino, aryl, heteroaryl, aminocarbonyl, carboxyl, and (C1-C10)alkoxycarbonyl; or
taken together, R11 and R12 may form a 5, 6, or 7-membered carbocycle or heterocycle wherein said carbocycle or heterocycle may be optionally substituted with R2;
R2 is selected from the group consisting of: halogen, (C1-C4)alkyl, halo(C1-C4)alkyl, hydroxy, (C1-C4)alkoxy, halo(C1-C4)alkoxy, carboxy, amino, (C1-C4)alkylamino and di(C1-C4)alkylamino;
Y is selected from,

L and L? are independently a bond or (CR3R4)m where R3 and R4 are independently selected from the group consisting of H and (C1-C4)alkyl, and m is 1 or 2;
R10 is chosen from alkyl, carbocycle and heterocycle, wherein said alkyl, carbocycle or heterocycle is optionally substituted with R7 and/or R8;
R20 is —C(?O)OR21;
R21 is chosen from H and (C1-C4)alkyl;
R5 and R6 are independently selected from the group consisting of hydrogen, hydroxy, (C1-C10) hydrocarbyl, halo(C1-C10)hydrocarbyl, and (C1-C10)alkoxy;
R7 and R8 are independently selected from the group consisting of: hydroxy, halogen, (C1-C4)alkyl, halo(C1-C4)alkyl, hydroxy(C1-C4)alkyl, (C1-C4)alkoxy, halo(C1-C4)alkoxy, (C1-C4)alkylthio, (C1-C4)alkylcarbonyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, cyano, oxo, (C1-C4)alkylsulfonyl, amino, (C1-C4)alkylamino, di(C1-C4)alkylamino, (C1-C4)acylamino, aminocarbonyl, carboxyl, and (C1-C4)alkoxycarbonyl, where each said alkyl, aryl, heteroaryl, cycloalkyl, or heterocycloalkyl, may be further optionally substituted with hydroxy, oxo, carboxy, carboxy(C1-C4)alkyl, hydroxy(C1-C4)alkyl, (C1-C4)alkoxy, (C1-C4)alkoxycarbonyl, (C1-C4)alkoxycarbonyl(C1-C4)alkyl, amino, (C1-C4)alkylamino, di (C1-C4)alkylamino, amido, (C1-C4)alkylamido, di (C1-C4)alkylamido, halogen, (C1-C4)alkyl, halo(C1-C4)alkyl, aryl, heteroaryl, heterocycloalkyl, or cycloalkyl;
or, taken together, R5 and R6, or R7 and R8 may form a 5, 6, or 7-membered carbocycle or heterocycle, wherein said carbocycle or heterocycle is optionally substituted with R9;
R9 is selected from the group consisting of: halogen, (C1-C4)alkyl, halo(C1-C4)alkyl, hydroxy, (C1-C4)alkoxy, halo(C1-C4)alkoxy, amino, (C1-C4)alkylamino and di(C1-C4)alkylamino.
US Pat. No. 10,280,408

METHOD OF SUPPRESSING GENE TRANSCRIPTION THROUGH HISTONE LYSINE METHYLATION

ICAHN SCHOOL OF MEDICINE ...

1. A pharmaceutical composition for human administration comprising a purified fusion protein comprising a Chlorella virus SET domain of a viral histone lysine methyltransferase protein (vSET), or of a vSET-like protein, fused to a protein that binds to a target gene, in a pharmaceutically acceptable carrier.