# US 11,078,287 B2 · Binding agonist for treatment of neurological and other disorders

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- Number: US 11,078,287 B2
- Document ID: US11078287B2
- Status: Granted
- Kind: B2
- Application number: 15/776,493
- Filed: 2016-11-15
- Published: 2020-05-28
- Granted: 2021-08-03
- Earliest claimed: 2015-11-17
- Assignees: GlaxoSmithKline Intellectual Property Development Limited
- Applicants: GlaxoSmithKline Intellectual Property Development Limited
- Inventors: Tejinder Kaur Bhinder; Chong Ding; Xu Feng; Wenqing Jiang; Alan Peter Lewis; Yingli Ma; Guhan Nagappan; Radha Shah Parmar; Yangsheng Qiu; Liuqing Yang; Qing Zhang; Yanjiao Zhou
- Web page: https://patentgrep.com/patent/US11078287B2

## CPC

- C07K 16/286: {against neuromediator receptors, e.g. serotonin receptor, dopamine receptor}
- C07K 16/2863: {against receptors for growth factors, growth regulators}
- A61K 39/39541: {against normal tissues, cells}
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 21/02: Muscle relaxants, e.g. for tetanus or cramps
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/02: for peripheral neuropathies
- A61P 25/06: Antimigraine agents
- A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia
- A61P 25/16: Anti-Parkinson drugs
- A61P 25/20: Hypnotics; Sedatives
- A61P 25/22: Anxiolytics
- A61P 25/24: Antidepressants
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 27/00: Drugs for disorders of the senses
- A61P 27/02: Ophthalmic agents
- A61P 27/06: Antiglaucoma agents or miotics
- A61P 27/16: Otologicals
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A61K 2039/505: {comprising antibodies}
- C07K 16/2878: {against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/75: Agonist effect on antigen
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention relates to TrkB binding agonists, and to the use of such agonists in the treatment of neurological disorders and other disorders. The present invention also relates to specific TrkB binding agonists comprising CDRs, variable regions, heavy and light chains, and variant sequences thereof.

## Claims

### Claim 1

A method of treating sensorineural hearing loss in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of a TrkB agonist antibody comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises complementarity determining region (CDR) H1, CDRH2, and CDRH3 of SEQ ID NO: 6, SEQ ID NO: 7, and SEQ ID NO: 8, respectively, and the light chain variable region comprises CDRL1, CDRL2, and CDRL3 of SEQ ID NO: 3, SEQ ID NO: 4, and SEQ ID NO: 5, respectively.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the sensorineural hearing loss results from acoustic trauma.

### Claim 3 (depends on 1)

The method according to claim 1, wherein the sensorineural hearing loss is sensory hearing loss.

### Claim 4 (depends on 1)

The method according to claim 1, wherein the sensorineural hearing loss is neural (8th nerve related) hearing loss.

### Claim 5 (depends on 1)

The method according to claim 1, wherein the sensorineural hearing loss is hidden hearing loss.

### Claim 6 (depends on 1)

The method according to claim 1, wherein the sensorineural hearing loss is tinnitus.

### Claim 7 (depends on 1)

The method according to claim 1, wherein the sensorineural hearing loss is presbycusis.

### Claim 8 (depends on 1)

The method according to claim 1, wherein the TrkB agonist antibody is used in combination with cochlear implant.

### Claim 9 (depends on 1)

The method according to claim 1, wherein the TrkB agonist antibody is used in combination with a steroid.

### Claim 10 (depends on 1)

The method according to claim 1, wherein the TrkB agonist antibody is administered by the intracochlear route in a pharmaceutical composition.

### Claim 11 (depends on 1)

The method according to claim 1, wherein the TrkB agonist antibody is administered by the transtympanic route in a pharmaceutical composition.

### Claim 12 (depends on 1)

The method according to claim 1, wherein the TrkB agonist antibody comprises a light chain variable region comprising SEQ ID NO: 41 and a heavy chain variable region comprising SEQ ID NO: 40.

### Claim 13 (depends on 2)

The method according to claim 2, wherein the TrkB agonist antibody comprises a light chain variable region comprising SEQ ID NO: 41 and a heavy chain variable region comprising SEQ ID NO: 40.

### Claim 14 (depends on 3)

The method according to claim 3, wherein the TrkB agonist antibody comprises a light chain variable region comprising SEQ ID NO: 41 and a heavy chain variable region comprising SEQ ID NO: 40.

### Claim 15 (depends on 4)

The method according to claim 4, wherein the TrkB agonist antibody comprises a light chain variable region comprising SEQ ID NO: 41 and a heavy chain variable region comprising SEQ ID NO: 40.

### Claim 16 (depends on 5)

The method according to claim 5, wherein the TrkB agonist antibody comprises a light chain variable region comprising SEQ ID NO: 41 and a heavy chain variable region comprising SEQ ID NO: 40.

### Claim 17 (depends on 6)

The method according to claim 6, wherein the TrkB agonist antibody comprises a light chain variable region comprising SEQ ID NO: 41 and a heavy chain variable region comprising SEQ ID NO: 40.

### Claim 18 (depends on 7)

The method according to claim 7, wherein the TrkB agonist antibody comprises a light chain variable region comprising SEQ ID NO: 41 and a heavy chain variable region comprising SEQ ID NO: 40.