Neutralizing anti-tl1a monoclonal antibodies

{
  "publication_number": "US2026102485A1",
  "country": "US",
  "kind": "A1",
  "title": "Neutralizing anti-tl1a monoclonal antibodies",
  "abstract": "Described herein are methods and pharmaceutical compositions for the treatment of inflammatory bowel disease (IBD), Crohn's Disease (CD), ulcerative colitis (UC) and medically refractive-ulcerative colitis (MR-UC). In particular, disclosed are anti-TLI A antibodies useful for the treatment of IBD.",
  "claims": [
    "1. A nucleic acid encoding an antibody or antigen-binding fragment that specifically binds to a tumor necrosis factor-like protein 1A (TL1A) polypeptide, wherein said antibody or antigen-binding fragment comprises: a) a heavy chain comprising a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity determining region 2 (HCDR2), and a heavy chain complementarity determining region 3 (HCDR3), wherein i) the HCDR1 comprises a first amino acid sequence of DTYMH of SEQ ID NO. 6; ii) the HCDR2 comprises a second amino acid sequence of PASGH of SEQ ID NO. 7; and iii) the HCDR3 comprises a third amino acid sequence of SGGLPD of SEQ ID NO. 8; and b) a light chain comprising a light chain complementarity determining region I (LCDRI), a light chain complementarity determining region 2 (LCDR2), and a light chain complementarity determining region 3 (LCDR3), wherein i) the LCDR1 comprises a fourth amino acid sequence of ASSSVSYMY of SEQ ID NO.14; ii) the LCDR2 comprises a fifth amino acid sequence of ATSNLAS of SEQ ID NO. 15; and iii) the LCDR3 comprises a sixth amino acid sequence of GNPRT of SEQ ID NO. 16. 2. The nucleic acid of claim 1, wherein the antibody or antigen-binding fragment is a chimeric antibody, a CDR-grafted antibody, a humanized antibody, a Fab, a Fab′, a F(ab′)2, a Fv, a disulfide linked Fv, a scFv, a single domain antibody, a diabody, a multispecific antibody, a dual specific antibody, an anti-idiotypic antibody, a bispecific antibody, or a combination thereof. 3. The nucleic acid of claim 1, wherein the antibody or antigen-binding fragment is a humanized antibody. 4. The nucleic acid of claim 1, wherein the antibody or antigen-binding fragment is an immunoglobulin G (IgG). 5. The nucleic acid of claim 4, wherein the IgG comprises an IgG1. 6. The nucleic acid of claim 4, wherein the IgG comprises an IgG2. 7. A vector comprising a nucleic acid of claim 1 that encodes an antibody or antigen-binding fragment, wherein the antibody or antigen-binding fragment comprises: a) a heavy chain comprising a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity determining region 2 (HCDR2), and a heavy chain complementarity determining region 3 (HCDR3), wherein: i) the HCDR1 comprises a first amino acid sequence of DTYMH of SEQ ID NO. 6; ii) the HCDR2 comprises a second amino acid sequence of PASGH of SEQ ID NO. 7; and iii) the HCDR3 comprises a third amino acid sequence of SGGLPD of SEQ ID NO. 8; and b) a light chain comprising a light chain complementarity determining region I (LCDRI), a light chain complementarity determining region 2 (LCDR2), and a light chain complementarity determining region 3 (LCDR3), wherein: i) the LCDR1 comprises a fourth amino acid sequence of ASSSVSYMY of SEQ ID NO.14; ii) the LCDR2 comprises a fifth amino acid sequence of ATSNLAS of SEQ ID NO. 15; and iii) the LCDR3 comprises a sixth amino acid sequence of GNPRT of SEQ ID NO. 16. 8. The vector of claim 7, wherein the vector is an expression vector. 9. The vector of claim 7, wherein the vector is a recombinant vector. 10. A host cell comprising the nucleic acid of claim 1. 11. A host cell comprising the vector of claim 7. 12. A method of treating inflammatory bowel disease (IBD) in a subject comprising administering to the subject an antibody or antigen-binding fragment, wherein the antibody or antigen-binding fragment comprises: a) a heavy chain comprising a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity determining region 2 (HCDR2), and a heavy chain complementarity determining region 3 (HCDR3), wherein: i) the HCDR1 comprises a first amino acid sequence of DTYMH of SEQ ID NO. 6; ii) the HCDR2 comprises a second amino acid sequence of PASGH of SEQ ID NO. 7; and iii) the HCDR3 comprises a third amino acid sequence of SGGLPD of SEQ ID NO. 8; and b) a light chain comprising a light chain complementarity determining region I (LCDRI), a light chain complementarity determining region 2 (LCDR2), and a light chain complementarity determining region 3 (LCDR3), wherein: i) the LCDR1 comprises a fourth amino acid sequence of ASSSVSYMY of SEQ ID NO.14; ii) the LCDR2 comprises a fifth amino acid sequence of ATSNLAS of SEQ ID NO. 15; and iii) the LCDR3 comprises a sixth amino acid sequence of GNPRT of SEQ ID NO. 16. 13. The method of claim 12, wherein IBD is Crohn's Disease, ulcerative colitis, medically refractory ulcerative colitis. 14. The method of claim 12, wherein the subject overexpresses TL1A. 15. The method of claim 12, wherein the antibody or antigen-binding fragment is a chimeric antibody, a CDR-grafted antibody, a humanized antibody, a Fab, a Fab′, a F(ab′)2, a Fv, a disulfide linked Fv, a scFv, a single domain antibody, a diabody, a multispecific antibody, a dual specific antibody, an anti-idiotypic antibody, a bispecific antibody, or a combination thereof. 16. The method of claim 12, wherein the antibody or antigen-binding fragment is a humanized antibody. 17. The method of claim 12, wherein the antibody or antigen-binding fragment is an immunoglobulin G (IgG). 18. The method of claim 17, wherein the IgG comprises an IgG1. 19. The method of claim 17, wherein the IgG comprises an IgG2."
  ],
  "description_excerpt": "Inflammatory bowel disease (IBD) refers to a collection of intestinal disorders causing inflammatory conditions in the gastrointestinal tract. The primary types of IBD are ulcerative colitis (UC) and Crohn's Disease (CD). These diseases are prevalent, with about 1.86 billion people diagnosed globally with UC, and about 1.3 million people diagnosed globally with CD. Unfortunately, there are a limited number of therapies available for IBD patients, and the development of new therapeutics has been hampered by sub-optimal results in clinical trials. Accordingly, there is a need for novel therapeutics to treat IBD.\n\nThe present disclosure provides antibodies useful for the treatment of IBD. In one aspect, provided is an antibody or antigen-binding fragment that specifically binds to a TL1A polypeptide. In some embodiments, the antibody or antigen-binding fragment comprises: a heavy chain comprising complementarity determining regions (CDRs) of SEQ ID NOs: 6-8 and a light chain comprising complementarity determining regions (CDRs) of SEQ ID NOs: 14-16. In some embodiments, the antibody or antigen-binding fragment comprises: a heavy chain comprising complementarity determining regions (CDRs) of SEQ ID NOs: 22-24 and a light chain comprising complementarity determining regions (CDRs) of SEQ ID NOs: 30-32.",
  "cpc": [
    "A61K 39/39533",
    "A61K 2039/505",
    "A61K 39/3955",
    "A61K 48/005",
    "A61P 1/02",
    "A61P 29/00",
    "A61P 37/00",
    "C07K 16/241",
    "C07K 16/2809",
    "C07K 16/2875",
    "C07K 2317/24",
    "C07K 2317/33",
    "C07K 2317/56",
    "C07K 2317/565",
    "C07K 2317/76",
    "C07K 2317/90",
    "C07K 2317/92"
  ],
  "ipc": [
    "A61K 39/00",
    "A61K 39/395",
    "A61K 48/00",
    "A61P 1/02",
    "A61P 29/00",
    "A61P 37/00",
    "C07K 16/24",
    "C07K 16/28"
  ],
  "assignees": [
    "Cedars Sinai Medical Center"
  ],
  "inventors": [
    "Janine Bilsborough",
    "Stephan R. Targan",
    "Bradley Henkle"
  ],
  "filing_date": "2025-09-22",
  "publication_date": "2026-04-16",
  "priority_date": "2016-10-26",
  "application_number": "US-202519336225-A",
  "family_id": "61971087",
  "cited_by_count": 0
}