# US 2013/0157945 A1 · Peptides targeting tnf family receptors and antagonizing tnf action, compositions, methods and uses thereof

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- Number: US 2013/0157945 A1
- Document ID: US20130157945A1
- Status: Published application
- Kind: A1
- Application number: 13/739,721
- Filed: 2013-01-11
- Published: 2013-06-20
- Earliest claimed: 2009-04-17
- Assignees: New York University School of Medicine
- Inventors: Chuanju LIU
- Web page: https://patentgrep.com/patent/US20130157945A1

## CPC

- A61K 38/18: Growth factors; Growth regulators
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 49/0008: {Screening agents using (non-human) animal models or transgenic animal models or chimeric hosts, e.g. Alzheimer disease animal model, transgenic model for heart failure}
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 17/06: Antipsoriatics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 19/10: for osteoporosis
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 27/02: Ophthalmic agents
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/00: Antineoplastic agents
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 14/475: Growth factors; Growth regulators
- G01N 33/5008: {for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics}
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- C07K 2319/00: Fusion polypeptide
- G01N 2333/525: Tumor necrosis factor [TNF]
- G01N 2500/10: involving cells
- 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
- 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)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The present invention provides modulators of TNF, particularly peptides and their derivatives, particularly GEP peptides, which antagonize TNF and TNF-mediated responses, activity or signaling. The invention provides methods of antagonizing TNF and the modulation of TNF-mediated diseases or responses, including inflammatory diseases and conditions. Compositions of GEP peptides, including in combination with other inflammatory mediators, are provided. Methods of treatment, alleviation, or prevention of TNF-mediated diseases and inflammatory conditions, including rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, psoriasis, inflammatory bowel diseases, Chrohn's disease, ulcerative colitis, uveitis, inflammatory lung diseases, chronic obstructive pulmonary disease, are provided.

## Claims

### Claim at position 1

1-21. (canceled)

### Claim 22

An isolated peptide comprising
(a) one or more granulin units of Granulin/epithelin precursor (GEP) selected from the group consisting of: granulin units F (amino acids 126-178 of SEQ ID NO: 1), A (amino acids 284-335 of SEQ ID NO: 1), and C (amino acids 366-416 of SEQ ID NO: 1); and
(b) one or more linker units of GEP,
wherein the peptide antagonizes TNFR1 or TNFR2 signaling, and wherein the peptide is a portion or mixed portion of the full-length GEP sequence.

### Claim 23 (depends on 22)

The isolated peptide of claim 22 comprising the granulin units of GEP: F (amino acids 126-178 of SEQ ID NO: 1), A (amino acids 284-335 of SEQ ID NO: 1), and C (amino acids 366-416 of SEQ ID NO: 1).

### Claim 24 (depends on 22)

The isolated peptide of claim 22, wherein the one or more linker units are selected from the group consisting of:
(a) linker unit P3 (amino acids 179-205 of SEQ ID NO: 1);
(b) linker unit P4 (amino acids 262-283 of SEQ ID NO: 1); and
(c) linker unit P5 (amino acids 336-365 of SEQ ID NO: 1).

### Claim 25 (depends on 22)

The isolated peptide of claim 22, comprising:
(a) F (amino acids 126-178 of SEQ ID NO: 1) and P3 (amino acids 179-205 of SEQ ID NO: 1) of GEP;
(b) A (amino acids 284-335 of SEQ ID NO: 1) and P4 (amino acids 262-283 of SEQ ID NO: 1) of GEP; or
(c) C (amino acids 366-416 of SEQ ID NO: 1) and P5 (amino acids 336-365 of SEQ ID NO: 1) of GEP.

### Claim 26 (depends on 22)

The isolated peptide of claim 22, comprising:
(a) amino acids 126-205 of SEQ ID NO: 1;
(b) amino acids 262-335 of SEQ ID NO: 1; or
(c) amino acids 336-416 of SEQ ID NO: 1.

### Claim 27 (depends on 22)

The isolated peptide of claim 22, comprising:
(a) F (amino acids 126-178 of SEQ ID NO: 1) and P3 (amino acids 179-205 of SEQ ID NO: 1) of GEP;
(b) A (amino acids 284-335 of SEQ ID NO: 1) and P4 (amino acids 262-283 of SEQ ID NO: 1) of GEP; and
(c) C (amino acids 366-416 of SEQ ID NO: 1) and P5 (amino acids 336-365 of SEQ ID NO: 1) of GEP.

### Claim 28 (depends on 22)

The isolated peptide of claim 22, comprising:
(a) amino acids 126-205 of SEQ ID NO: 1;
(b) amino acids 262-335 of SEQ ID NO: 1; and
(c) amino acids 336-416 of SEQ ID NO: 1.

### Claim 29 (depends on 22)

A pharmaceutical composition comprising the isolated peptide of claim 22 and a pharmaceutically acceptable carrier, vehicle, or diluent.

### Claim 30 (depends on 29)

The composition of claim 29 further comprising one or more of an anti-inflammatory agent or compound, an anti-cancer agent or compound, and an immunomodulatory agent.

### Claim 31

An isolated peptide comprising:
(a) a fragment of GEP selected from the group consisting of: at least ½F (amino acids 153-178 of SEQ ID NO: 1); at least ½A (amino acids 284-304 of SEQ ID NO: 1); and at least ½C (amino acids 366-392 of SEQ ID NO: 1); and
(b) one or more linker units of GEP,
wherein the peptide antagonizes TNFR1 or TNFR2 signaling, and wherein the peptide is a portion or mixed portion of the full-length GEP sequence.

### Claim 32 (depends on 31)

The isolated peptide of claim 31, comprising:
(a) ½F (amino acids 153-178 of SEQ ID NO: 1) and P3 (amino acids 179-205 of SEQ ID NO: 1) of GEP;
(b) ½A (amino acids 284-304 of SEQ ID NO: 1) and P4 (amino acids 262-283 of SEQ ID NO: 1) of GEP; or
(c) ½C (amino acids 366-392 of SEQ ID NO: 1) and P5 (amino acids 336-365 of SEQ ID NO: 1) of GEP.

### Claim 33 (depends on 31)

The isolated peptide of claim 31, comprising:
(a) amino acids 153-205 of SEQ ID NO: 1;
(b) amino acids 262-304 of SEQ ID NO: 1; or
(c) amino acids 335-392 of SEQ ID NO: 1.

### Claim 34 (depends on 31)

The isolated peptide of claim 31, comprising:
(a) amino acids 153-205 of SEQ ID NO: 1;
(b) amino acids 262-304 of SEQ ID NO: 1; and
(c) amino acids 335-392 of SEQ ID NO: 1.

### Claim 35 (depends on 31)

A pharmaceutical composition comprising the isolated peptide of claim 31 and a pharmaceutically acceptable carrier, vehicle, or diluent.

### Claim 36 (depends on 35)

The composition of claim 35 further comprising one or more of an anti-inflammatory agent or compound, an anti-cancer agent or compound, and an immunomodulatory agent.