# US 10,308,703 B2 · Variants of DR3 and use thereof

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- Number: US 10,308,703 B2
- Document ID: US10308703B2
- Status: Granted
- Kind: B2
- Application number: 15/306,822
- Filed: 2015-04-27
- Published: 2017-04-27
- Granted: 2019-06-04
- Earliest claimed: 2014-04-28
- Assignees: The National Institute for Biotechnology I
- Applicants: The National Institute for Biotechnology In the Negev Ltd.
- Inventors: Amir Aharoni; Itay Levin
- Web page: https://patentgrep.com/patent/US10308703B2

## CPC

- C07K 14/70578: {NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 (NGF-receptor C07K14/71, TNF-receptor C07K14/7151)}
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- C07K 14/715: for cytokines; for lymphokines; for interferons
- 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 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)

## Abstract

Death-domain receptor 3 (DR3) variants having increased binding affinity to TL1A, and composition comprising same, are provided. Further, methods of use of said peptides or composition, including, but not limited to treatment of autoimmune and/or inflammatory disease are provided.

## Claims

### Claim 1

An amino acid molecule, comprising the amino acid sequence of GGTRSPRCDCAGDFHKKIGLFCCRGCPAGHYLKAPCTEPCGNSTCLVCPQDTFLAWE NHHNSECARCQACDEQASQVALENCSAVADTRCGCKPGWFVECQVSQCVSSSPFYCQ PCLDCGALHRHTRLLCSRRDTDCGTCLPGFYEHGDGCVSCPTSTLGSCPERCAAVCGW RQMF set forth in SEQ ID NO: 2.

### Claim 2 (depends on 1)

The amino acid molecule of claim 1, having an increased binding affinity to human TNF-like 1A (TL1A), compared to SEQ ID NO: 13.

### Claim 3 (depends on 1)

The amino acid molecule of claim 1, further comprising a peptide of the Fragment crystallizable (Fc) region of an antibody, optionally wherein said peptide of the Fragment crystallizable (Fc) region of an antibody comprises the amino acid sequence of VECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGV EVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAK GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL DSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEGLHNHYTQKSLSLSPGK set forth in SEQ ID NO: 10.

### Claim 4 (depends on 3)

The amino acid molecule of claim 3, further comprising a linker comprising the amino acid sequence of IEGRMDRS set forth in SEQ ID NO: 11, wherein said linker is fused to the carboxy terminus of said amino acid of SEQ ID NO: 2 and to the amino terminus of said peptide of the Fc region of an antibody.

### Claim 5 (depends on 1)

A composition comprising the amino acid molecule of claim 1 and a carrier.

### Claim 6 (depends on 4)

A polynucleotide molecule comprising a coding portion encoding the amino acid molecule of claim 4.

### Claim 7 (depends on 6)

An expression vector comprising the polynucleotide of claim 6.

### Claim 8 (depends on 7)

An isolated cell comprising the expression vector of claim 7.

### Claim 9 (depends on 7)

A composition comprising the expression vector of claim 7 and a carrier.

### Claim 10 (depends on 5)

A method of inhibiting TL1A-induced secretion of IFN-γ in a subject in need thereof, comprising the step of administering to said subject an effective amount of the composition of claim 5.