# US 11,306,122 B2 · Compositions and methods of inhibiting the binding of plasma IgG autoantibodies to serotonin 2A receptor

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- Number: US 11,306,122 B2
- Document ID: US11306122B2
- Status: Granted
- Kind: B2
- Application number: 16/897,071
- Filed: 2020-06-09
- Published: 2020-12-17
- Granted: 2022-04-19
- Earliest claimed: 2019-06-14
- Assignees: The United States Government as represented by the Department of Veterans Affairs
- Applicants: United States Government As Represented By The Department of Veterans Affairs
- Inventors: Mark B. Zimering
- Web page: https://patentgrep.com/patent/US11306122B2

## CPC

- C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68)
- A61K 31/445: Non condensed piperidines, e.g. piperocaine
- A61K 31/517: ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
- A61K 38/10: Peptides having 12 to 20 amino acids {(A61K38/043 - A61K38/046 take precedence)}
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 9/12: Antihypertensives
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/16: Anti-Parkinson drugs
- A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A61P 25/20: Hypnotics; Sedatives
- 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 27/06: Antiglaucoma agents or miotics
- C07K 14/70571: {for neuromediators, e.g. serotonin receptor, dopamine receptor}
- 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

Disclosed herein, are decoy peptides or polypeptides capable of inhibiting binding of 5-HT2A autoantibodies to a second extracellular loop region of the 5-HT2A receptor, and a pharmaceutical composition containing the decoy peptides or polypeptides and methods of use.

## Claims

### Claim 1

A decoy peptide consisting of the sequence of QDDSKVFKEGSCLLADDN (SEQ ID NO: 1), or a fragment thereof, wherein the fragment of SEQ ID NO: 1 consists of 4 to 9 amino acids in length, and wherein the decoy peptide inhibits the binding of 5-HT2A receptor autoantibodies to a second extracellular loop region of the 5-HT2A receptor.

### Claim 2 (depends on 1)

The decoy peptide of claim 1, wherein the fragment of SEQ ID NO: 1 consists of the sequence SCLLADDN (SEQ ID NO: 2), QDDSKVF (SEQ ID NO: 3), or VFKEGSC (SEQ ID NO: 4).

### Claim 3 (depends on 1)

The decoy peptide of claim 1, wherein the decoy peptide inhibits the binding of a 5-HT2A receptor autoantibodies to a second extracellular loop region of the 5-HT2A receptor by competitive inhibition.

### Claim 4 (depends on 1)

The decoy peptide of claim 1, wherein at least one amino acid residue of the decoy peptide comprises an acetyl group, a fluorenylmethoxy carbonyl group, a formyl group, a palmitoyl group, a myristyl group, a stearyl group, or polyethylene glycol.

### Claim 5 (depends on 1)

A pharmaceutical composition comprising the decoy peptide of claim 1, and a pharmaceutically acceptable carrier.

### Claim 6

A method of treating a subject with a disease or disorder, the method comprising: administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising a decoy peptide comprising the sequence of SEQ ID NO: 2 and a pharmaceutically acceptable carrier, wherein the disease or disorder is a metabolic disease or disorder, a cardiovascular or a microvascular disease or disorder, or a neurodegenerative disease or disorder.

### Claim 7 (depends on 6)

The method of claim 6, wherein the cardiovascular or the microvascular disease or disorder is a stroke, kidney dysfunction, kidney failure, age-related macular degeneration, diabetic macular edema, diabetic nephropathy, microvascular angiopathy, hypertension, painful neuropathy, or hypertensive nephropathy.

### Claim 8 (depends on 6)

The method of claim 6, wherein the neurodegenerative disease or disorder is open angle glaucoma, dementia, Parkinson's disease, macular degeneration, or retinal degeneration.

### Claim 9 (depends on 6)

The method of claim 6, wherein the metabolic disease or disorder is diabetes.

### Claim 10 (depends on 6)

The method of claim 6, wherein the subject is obese or has a traumatic brain injury, type 2 diabetes, hypertension, microvascular angiopathy, painful neuropathy, Parkinson's disease, dementia, major depressive disorder, schizophrenia, retinitis pigmentosa, refractory hypertension, mild cognitive dysfunction, primary open angle glaucoma or previously had a stroke or a traumatic brain injury or a combination thereof.

### Claim 11 (depends on 6)

The method of claim 6, wherein the subject has one or more 5-HT2A receptor autoantibodies.

### Claim 12 (depends on 6)

The method of claim 6, wherein administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising a decoy peptide comprising SEQ ID NO: 2 and a pharmaceutically acceptable carrier lowers blood pressure in the subject.

### Claim 13 (depends on 6)

The method of claim 6, wherein the administration of the therapeutically effective amount of the pharmaceutical composition promotes or induces weight loss in the subject or improves short term memory in the subject.

### Claim 14 (depends on 6)

The method of claim 6, further comprising administering a therapeutically effective amount of ketanserin or volinanserin to the subject.

### Claim 15 (depends on 6)

The method of claim 6, wherein at least one amino acid residue of the decoy peptide comprises an acetyl group, a fluorenylmethoxy carbonyl group, a formyl group, a palmitoyl group, a myristyl group, a stearyl group, or polyethylene glycol.

### Claim 16

A method of treating a subject with a neurologic disease or disorder, the method comprising: administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising a decoy peptide comprising the sequence of SEQ ID NO: 2 and a pharmaceutically acceptable carrier, wherein the neurologic disease or disorder is neuropathy, dementia, major depressive disorder or Parkinson's disease.

### Claim 17 (depends on 16)

The method of claim 16, further comprising administering a therapeutically effective amount of ketanserin or volinanserin to the subject.

### Claim 18 (depends on 16)

The method of claim 16, wherein at least one amino acid residue of the decoy peptide comprises an acetyl group, a fluorenylmethoxy carbonyl group, a formyl group, a palmitoyl group, a myristyl group, a stearyl group, or polyethylene glycol.

### Claim 19

A method of inducing sedation in a subject, the method comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising a decoy peptide comprising SEQ ID NO: 2, and a pharmaceutically acceptable carrier.

### Claim 20 (depends on 19)

The method of claim 19, wherein at least one amino acid residue of the decoy peptide comprises an acetyl group, a fluorenylmethoxy carbonyl group, a formyl group, a palmitoyl group, a myristyl group, a stearyl group, or polyethylene glycol.