# US 11,440,954 B2 · Optimized anti-TL1A antibodies

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- Number: US 11,440,954 B2
- Document ID: US11440954B2
- Status: Granted
- Kind: B2
- Application number: 16/863,971
- Filed: 2020-04-30
- Published: 2020-08-13
- Granted: 2022-09-13
- Earliest claimed: 2018-04-25
- Assignees: Prometheus Biosciences, Inc.; Cedars-Sinai Medical Center
- Applicants: Prometheus Biosciences, Inc.; Cedars-Sinai Medical Center
- Inventors: Jeffry D. Watkins; Cindy T. Dickerson; J. Monty Watkins; Patricia McNeeley; Janine Bilsborough; Bradley Henkle; Stephan R. Targan
- Web page: https://patentgrep.com/patent/US11440954B2

## CPC

- C07K 16/24: against cytokines, lymphokines or interferons
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- C07K 16/241: {Tumor Necrosis Factors}
- C07K 16/28: against receptors, cell surface antigens or cell surface determinants
- C07K 16/2875: {against the NGF/TNF superfamily, e.g. CD70, CD95L, CD153, CD154 (against NGF C07K16/22, against TNF C07K16/241)}
- C12N 5/10: Cells modified by introduction of foreign genetic material
- C12N 15/09: Recombinant DNA-technology
- C12N 15/63: Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/52: Constant or Fc region; Isotype
- C07K 2317/524: CH2 domain
- C07K 2317/55: Fab or Fab'
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/71: Decreased effector function due to an Fc-modification
- C07K 2317/732: Antibody-dependent cellular cytotoxicity [ADCC]
- C07K 2317/734: Complement-dependent cytotoxicity [CDC]
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/90: characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- 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
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

Described herein are humanized anti-TL1A antibodies and pharmaceutical compositions for the treatment of inflammatory bowel disease (IBD), such as Crohn's Disease (CD) and ulcerative colitis (UC).

## Claims

### Claim 1

A nucleic acid encoding an antibody, or antigen binding portion thereof, that binds to tumor necrosis factor-like ligand 1A (TL1A), wherein the nucleic acid comprises:
a nucleic acid sequence encoding a heavy chain variable region comprising: (a) a nucleic acid encoding a HCDR1 comprising the amino acid sequence set forth by SEQ ID NO: 553; (b) a nucleic acid encoding a HCDR2 comprising an amino acid sequence set forth by any one of SEQ ID NOs: 554 to 564, or 574 to 577; and (c) a nucleic acid encoding a HCDR3 comprising an amino acid sequence set forth by any one of SEQ ID NOs: 565 to 568, or 579 to 581; and
a nucleic acid sequence encoding a light chain variable region comprising: (a) a nucleic acid encoding a LCDR1 comprising an amino acid sequence set forth by any one of SEQ ID NOs: 569 or 570; (b) a nucleic acid encoding a LCDR2 comprising the amino acid sequence set forth by SEQ ID NO: 488; and (c) a nucleic acid encoding a LCDR3 comprising the amino acid sequence set forth by SEQ ID NO: 572.

### Claim 2 (depends on 1)

The nucleic acid encoding the antibody or antigen binding portion of claim 1, wherein the HCDR2 comprises the amino acid sequence as set forth by SEQ ID NO: 554.

### Claim 3 (depends on 1)

The nucleic acid encoding the antibody or antigen binding portion of claim 1, wherein the HCDR2 comprises the amino acid sequence as set forth by SEQ ID NO: 555.

### Claim 4 (depends on 1)

The nucleic acid encoding the antibody or antigen binding portion of claim 1, wherein the HCDR3 comprises the amino acid sequence as set forth by SEQ ID NO: 565.

### Claim 5 (depends on 1)

The nucleic acid encoding the antibody or antigen binding portion of claim 1, wherein the HCDR3 comprises the amino acid sequence as set forth by SEQ ID NO: 566.

### Claim 6 (depends on 1)

The nucleic acid encoding the antibody or antigen binding portion of claim 1, wherein the LCDR1 comprises the amino acid sequence as set forth by SEQ ID NO: 569.

### Claim 7 (depends on 1)

The nucleic acid encoding the antibody or antigen binding portion of claim 1, wherein the nucleic acid sequence encoding the heavy chain variable region comprises a nucleic acid encoding for a heavy chain constant region, and the nucleic acid sequence encoding the light chain variable region comprises a nucleic acid encoding for a light chain constant region.

### Claim 8 (depends on 1)

A recombinant vector comprising the nucleic acid of claim 1.

### Claim 9 (depends on 8)

The recombinant vector of claim 8, wherein the recombinant vector is a plasmid.

### Claim 10 (depends on 8)

The recombinant vector of claim 8, wherein the recombinant vector is an expression vector.

### Claim 11 (depends on 8)

A host cell comprising the recombinant vector of claim 8.

### Claim 12

A nucleic acid encoding an antibody, or antigen binding portion thereof, that binds to tumor necrosis factor-like ligand 1A (TL1A), wherein the nucleic acid comprises:
a nucleic acid sequence encoding a heavy chain variable region comprising: (a) a nucleic acid encoding a HCDR1 comprising the amino acid sequence set forth by SEQ ID NO: 553; (b) a nucleic acid encoding a HCDR2 comprising the amino acid sequence set forth by SEQ ID NO: 554; and (c) a nucleic acid encoding a HCDR3 comprising the amino acid sequence set forth by SEQ ID NO: 565; and
a nucleic acid sequence encoding a light chain variable region comprising: (a) a nucleic acid encoding a LCDR1 comprising the amino acid sequence set forth by SEQ ID NO: 569; (b) a nucleic acid encoding a LCCR2 comprising the amino acid sequence set forth by SEQ ID NO: 488; and (c) a nucleic acid encoding a LCDR3 comprising the amino acid sequence set forth by SEQ ID NO: 572.

### Claim 13 (depends on 12)

The nucleic acid encoding the antibody or antigen binding portion of claim 12, wherein the nucleic acid sequence encoding the heavy chain variable region comprises a nucleic acid encoding for a heavy chain constant region, and the nucleic acid sequence encoding the light chain variable region comprises a nucleic acid encoding for a light chain constant region.

### Claim 14 (depends on 12)

A recombinant vector comprising the nucleic acid of claim 12.

### Claim 15 (depends on 14)

The recombinant vector of claim 14, wherein the recombinant vector is a plasmid.

### Claim 16 (depends on 14)

The recombinant vector of claim 14, wherein the recombinant vector is an expression vector.

### Claim 17 (depends on 14)

A host cell comprising the recombinant vector of claim 14.

### Claim 18

A method of producing an antibody, or an antigen binding portion thereof, that binds to tumor necrosis factor-like ligand 1A (TL1A), wherein the method comprises
(a) providing a host cell comprising an expression vector harboring a nucleic acid encoding the antibody, or the antibody binding portion thereof, wherein the nucleic acid comprises:
a nucleic acid sequence encoding a heavy chain variable region comprising: (i) a nucleic acid encoding a HCDR1 comprising the amino acid sequence set forth by SEQ ID NO: 553; (ii) a nucleic acid encoding a HCDR2 comprising the amino acid sequence set forth by SEQ ID NO: 554; and (iii) a nucleic acid encoding a HCDR3 comprising the amino acid sequence set forth by SEQ ID NO: 565; and
a nucleic acid sequence encoding a light chain variable region comprising: (i) a nucleic acid encoding a LCDR1 comprising the amino acid sequence set forth by SEQ ID NO: 569; (ii) a nucleic acid encoding a LCCR2 comprising the amino acid sequence set forth by SEQ ID NO: 488; and (iii) a nucleic acid encoding a LCDR3 comprising the amino acid sequence set forth by SEQ ID NO: 572; and
(b) culturing the host cell under conditions to induce expression of the antibody or antibody portion from the host cell.

### Claim 19 (depends on 18)

The method of claim 18, further comprising harvesting the antibody or antigen binding portion.

### Claim 20 (depends on 19)

The method of claim 19, further comprising purifying the harvested antibody or antigen binding portion.