US Pat. No. 9,796,730

HALOGENATED BENZOXAZINES AND THEIR USE

EBERHARD KARLS UNIVERSITA...

1. Radioactive tracer of the formula

in which,
X and Y independently from one another represent CH, CH2, N, S or O,

wherein X and Y are not simultaneously CH or CH2,

wherein, if X represents CH or N, the dotted line between X and the neighboring atom represents a bond, and
wherein, if Y represents CH or N, the dotted line between Y and the neighboring atom represents a bond,
R1 and R2 independently from one another are selected from the group consisting of (C1-C2)-alkyl, (C1-C2)-alkoxy and (C1-C2)-alkyl sulfonyl,

wherein alkyl, alkoxy and alkyl sulfonyl can be substituted with one up to three substituents selected from the group consisting
of 76Br, 75Br, 19F and 18F,

R3, R4, R7, R8, R9 and R10 independently from one another are selected from the group consisting of hydrogen, halogen, hydroxy, amino, cyano, nitro,
(C1-C4)-alkyl, (C1-C4)-alkyl amino and (C1-C4)-alkoxy,

wherein alkyl and alkoxy can be substituted with one up to three substituents selected from group consisting of 76Br, 75Br, 19F and 18F,

R5, if X represents CH or N, represents a substituent selected from the group consisting of hydrogen, halogen, hydroxy, amino,
cyano, nitro, (C1-C4)-alkyl, (C1-C4)-alkyl amino and (C1-C4)-alkoxy,

wherein alkyl and alkoxy can be substituted with one up to three substituents selected from group consisting of 76Br, 75Br, 19F and 18F,

R5, if X represents CH2, S or O, represents two substituents independently from one another selected from the group consisting of hydrogen, halogen,
hydroxy, amino, cyano, nitro, (C1-C4)-alkyl, (C1-C4)-alkyl amino and (C1-C4)-alkoxy,

wherein alkyl and alkoxy can be substituted with one up to three substituents selected from group consisting of 76Br, 75Br, 19F and 18F,

R6, if X represents CH or N, represents a substituent selected from the group consisting of hydrogen, halogen, hydroxy, amino,
cyano, nitro, (C1-C4)-alkyl, (C1-C4)-alkyl amino and (C1-C4)-alkoxy,

wherein alkyl and alkoxy can be substituted with one up to three substituents selected from group consisting of 76Br, 75Br, 19F and 18F,

R6, if Y represents CH2, S or O, represents two substituents independently from one another selected from the group consisting of hydrogen, halogen,
hydroxy, amino, cyano, nitro, (C1-C4)-alkyl, (C1-C4)-alkyl amino and (C1-C4)-alkoxy,

wherein alkyl and alkoxy can be substituted with one up to three substituents selected from group consisting of 76Br, 75Br, 19F and 18F,

wherein the radioactive tracer of the formula (I) comprises at least one substituent selected from the group consisting of
76Br, 75Br, 19F and 18F,

and the salts thereof, the solvates thereof and the solvates of the salts thereof.
US Pat. No. 9,599,616

CELL SELECTION METHOD AND CELLS OBTAINED THEREFROM

Eberhard Karls Universita...

1. Method for the in vitro selection of at least one therapeutic highly migrative cell subpopulation from an original cell
population of eukaryotic cells, wherein the therapeutic cell subpopulation can be used for the treatment of diseases of tissues
or organs, and wherein the method has the following consecutive steps:
a) adding an original cell population to a first starting reservoir, which is connected via at least one selection means having
at least one opening to at least one second selection reservoir, wherein the at least one opening of the at least one selection
means has a diameter of 3 ?m to 500 ?m;

b) adding at least one cell culture medium to the at least one selection reservoir to which the therapeutic cell subpopulation
migrates;

c) culturing the original cell population for a period of 15 minutes to 48 hours, within which period a cell subpopulation
migrates through the at least one opening of the selection means towards the at least one selection reservoir;

d) selecting and obtaining a cell, which is selected from cells that migrated as the first to the one hundred thousandth cell
through the at least one opening of the selection means into the at least one selection reservoir, in order to obtain a cell
subpopulation with an elevated migration potential or tropism to a certain cell type compared to the original cell population;
and

e) selecting a highly migrative cell subpopulation from the cell subpopulation obtained in step d) using at least one agent
that specifically binds to a cell marker that is a cell surface marker or an internal cell marker, thereby isolating the highly
migrative therapeutic subpopulation.

US Pat. No. 9,829,481

SENESCENCE TRACERS

EBERHARD KARLS UNIVERSITA...

1. Compound of formula
A-L-M  (I)
in which,
A represents

wherein,
* represents the binding site to the residue represented by L,
L represents *Y-(CH2)n-# or


wherein,
Y is selected from the group consisting of O, N, S, SO and SO2,

n is an integer from 2 to 6,
* represents the binding site to the residue represented by A, and
# represents the binding site to the residue represented by M, and

M represents a fluorophore, a residue comprising at least one atom selected from the group consisting of 76Br, 75Br, 18F, 13C and 11C or a combination thereof,
and the salts thereof, the solvates thereof and the solvates of the salts thereof.

US Pat. No. 9,701,941

CELL SELECTION METHOD AND CELLS OBTAINED THEREFROM

Eberhard Karls Universita...

1. A method for the in vitro selection of at least one therapeutic mesenchymal stem cell, wherein the therapeutic mesenchymal
stem cell is from a mesenchymal stem cell subpopulation selected from an original mesenchymal stem cell population, wherein
the therapeutic mesenchymal stem cell can be used for the treatment of diseases of tissues or organs, and wherein the method
has the following consecutive steps:
a) adding an original mesenchymal stem cell population to a first starting reservoir, which is connected via at least one
selection means having at least one opening to at least two selection reservoirs, wherein the at least one opening of the
at least one selection means has a diameter of 8 ?m to 12 ?m;

b) adding at least one cell culture medium to the at least two selection reservoirs;
c) culturing the original mesenchymal stem cell population for a period of 15 min to 6 hours, within which period a mesenchymal
cell subpopulation migrates through the at least one opening of the selection means towards at least one of the at least two
selection reservoirs; and

d) selecting and obtaining at least one of the mesenchymal stem cells that migrated as the first to the one hundred thousandth
cell through the at least one opening of the selection means into at least one of the at least two selection reservoirs, in
order to obtain a mesenchymal stem cell with an elevated migration potential or tropism compared to the original mesenchymal
stem cell population,
thereby selecting the at least one therapeutic mesenchymal stem cell.
US Pat. No. 10,400,217

IMMORTALIZED CELL

EBERHARD KARLS UNIVERSITA...

1. An isolated, in vitro immortalized cranium periosteum cell, wherein the cell was deposited on 29 Nov. 2013 under the designation “Tag58” at the Deutsche Sammlung von Mikroorganismen and Zellkulturen GmbH, Braunschweig, Germany (DSMZ) under the accession number DSM ACC3218.

US Pat. No. 10,233,150

COMPOSITION FOR THE MODULATION OF THE ACTIVITY OF NON-STRUCTURE PROTEINS

Eberhard Karls Universita...

1. Method for the modulation of non-structural proteins, comprising the step of contacting said non-structural proteins with a composition comprising a 5-oxo-pyrrolidine-2-carboxylic acid derivative with the formula IwhereinR1 is selected from the group consisting of:
linear alkyl residue with C1-C6,

R2 and R3 are each independent from each other selected from the group consisting of:

with each:
n=0-20,
m=1-25, and
X=O or S.

US Pat. No. 10,280,140

PRODUCTION OF PYRROLIDINE DERIVATIVES

Eberhard Karls Universita...

1. A method for producing a pyrrolidine derivative, which comprises the following steps:1) Incubating
(a) 5-oxo-pyrrolidine-2-carboxylic acid derivative of formula I

 wherein
R1 is a linear alkyl residue with C1-C6;
R2 and R3 are each independent from each other selected from the group consisting of:

with each:
n =0- 20,
X ?O or S,
and
(b) a compound selected from the group consisting of:
N-substituted diamine of formula II

where R4 is a linear alkyl or acyl residue with C2 to C22, and n =1-6; and
N-substituted monoamine of formula III

where R5 is a linear alkyl or acyl residue with C2 to C22; and
N-substituted fatty amide of formula IV

where R6 is a linear alkyl group with C2 to C24;
under appropriate reaction conditions to obtain a pyrrolidine derivative, and
2) Isolating the obtained pyrrolidine derivative.
US Pat. No. 10,655,134

PRODUCTION OF RECOMBINANT EXPRESSION VECTORS

EBERHARD KARLS UNIVERSITA...

1. A method for the production of recombinant expression vectors, comprising the following steps:(1) providing a cell population containing a starting vector, said cell population expresses a first gene product encoded by the starting vector, whereas in the starting vector the coding nucleotide sequence for the first gene product is upstreamly and downstreamly flanked by first recombination nucleotide sequences;
(2) transfecting the cell population obtained from step (1) with a transfer vector encoding a second gene product, whereas in the transfer vector the coding nucleotide sequence for the second gene product is upstreamly and downstreamly flanked by second recombination nucleotide sequences which are homologous to said first recombination nucleotide sequences;
(3) incubating the cell population obtained from step (2) under conditions which allow an exchange of the coding nucleotide sequence for said first gene product against the coding nucleotide sequence for said second gene product by homologous recombination of said first and second recombination nucleotide sequences and the formation of a recombinant expression vector;
(4) incubating the cell population obtained from step (3) under conditions which allow the expression of said second gene product;
(5) contacting the cell population obtained from step (4) with a first binding molecule that binds to said first gene product under conditions which allow the formation of complexes of said first binding molecule and said first gene product;
(6) separating said complexes of first binding molecule and first gene product from the cell population;
(7) isolating the recombinant expression vectors from the cell population;
(8) incubating the recombinant expression vectors with non-transfected cells under conditions which allow a transfection of the non-transfected cells with said recombinant expression vectors to obtain a further transfected cell population;
(9) contacting said further transfected cell population with a second binding molecule which binds to the second gene product under conditions which allow the formation a complexes of the second binding molecule and the second gene product;
(10) separating said complexes of the second binding molecule and the second gene product; and
(11) repeating the steps (8) to (10) at least one additional time.
US Pat. No. 10,416,173

METHOD FOR THE DIAGNOSIS OF OR RISK FOR A DISEASE MEDIATED VIA THE ALTERNATIVE PATHWAY OF THE COMPLEMENT SYSTEM

Eberhard Karls Universita...

1. A method for detecting an isoform of complement factor D (isoCFD) in a living being, comprising the following steps:(1) providing a biological sample of the living being, and
(2) measuring the biological sample for the presence of at least one isoCFD, which consists of an amino acid sequence selected from the group consisting of: SEQ ID No. 3, SEQ ID No. 4, SEQ ID No. 5, and SEQ ID No. 6.

US Pat. No. 10,616,699

HEARING AID THAT CAN BE INTRODUCED INTO THE AUDITORY CANAL AND HEARING AID SYSTEM

EBERHARD KARLS UNIVERSITA...

1. A hearing aid configured to be inserted into an ear canal of a patient, comprising an actuator that effects a mechanical stimulation of the tympanic membrane, wherein the actuator comprises an inner surface associated with the tympanic membrane and an outer surface associated with the ear canal, the actuator being configured as an areal disk actuator, whose deformation stimulates the tympanic membrane by areal deformation; wherein the hearing aid is further configured to remain fixed at the tympanic membrane by the adhesive forces between the tympanic membrane and the actuator.