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CA-3114407-C - ANTI-HLA-G ANTIBODIES, COMPOSITIONS COMPRISING ANTI-HLA-G ANTIBODIES AND METHODS OF USING ANTI-HLA-G ANTIBODIES

CA3114407CCA 3114407 CCA3114407 CCA 3114407CCA-3114407-C

Abstract

Provided herein are antibodies that selectively bind to HLA-G and and compositions comprising the antibodies. Also provided are methods of using the antibodies, such as therapeutic and diagnostic methods.

Inventors

  • Courtney BEERS
  • John Corbin
  • Doug Hodges
  • Achim Moesta
  • Vanessa Soros
  • Paul Fredrick Widboom
  • Joseph Robert Warfield

Assignees

  • TIZONA THERAPEUTICS

Dates

Publication Date
20260505
Application Date
20190926
Priority Date
20180927

Claims (10)

  1. CLAIMS 1. An antibody that specifically binds to human HLA-G (hHLA-G), comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein a) the VH comprises: i) a VH-complementarity determining region (CDR) 1 comprising the amino acid sequence set forth in SEQ ID NO: 7; a VHCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 44; and a VHCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 93, wherein the CDRs are according to Chothia; or ii) a VHCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 25; a VHCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 65; and a VHCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 93, wherein the CDRs are according to Kabat; and b) the VL comprises: i) a VLCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 118; a VLCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 138; and a VLCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 155, wherein the CDRs are according to Chothia and Kabat.
  2. 2. The antibody of claim 1, comprising a VH sequence that is at least 85% identical to the amino acid sequence set forth in SEQ ID NO: 192 and a VL sequence that is at least 85% identical to the amino acid sequence set forth in SEQ ID NO: 220.
  3. 3. The antibody of claim 1, comprising a VH sequence that is at least 95% identical to the amino acid sequence set forth in SEQ ID NO: 192 and a VL sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 220.
  4. 4. The antibody of claim 1, wherein the antibody comprises a heavy chain of SEQ ID NO: 254 and a light chain of SEQ ID NO: 322.
  5. 5. The antibody of claim 1, wherein the antibody comprises a heavy chain of SEQ ID NO: 288 and a light chain of SEQ ID NO: 322.
  6. 6. The antibody of claim 1, wherein the antibody is a monoclonal antibody.
  7. 7. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier or excipient. 208 Date re�ue / Received date 2025-03-20
  8. 8. The pharmaceutical composition of claim 7, further comprising an effective amount of at least one of the following: a) an anti-ILT2 antibody; b) an anti-ILT4 antibody; c) an anti-KIR2DL4 antibody; d) an anti-HLA-E antibody; e) an anti-NKG2A antibody f) an anti-HLA-F antibody g) an anti-PD-L1 antibody; h) an anti-PD-1 antibody; i) an anti-CD38 antibody; j) an anti-CD39 antibody; k) an anti-CD73 antibody; l) an anti-A2A receptor antibody; m) an anti-A2B receptor antibody; n) an anti-A2A/A2B dual receptor antibody or a combination thereof; o) an anti-CD47 antibody; p) an anti-CTLA-4 antibody; q) an anti-TIM-3 antibody; r) an anti-TIGIT antibody; s) an anti-VISTA antibody; t) an anti-CD94 antibody; u) a small molecule inhibitor; v) an oncolytic virus; w) a chemotherapy; and/or x) ADCC capable therapies using effector competent antibodies selected from the group consisting of anti�CD19, anti-CD20, anti-EGFR, anti-Her2, anti-SLAMF7, anti-CD52, anti-BCMA, anti-GD2, and anti-CCR4.
  9. 9. The pharmaceutical composition of claim 8, further comprising one or both of a) an antibody to an immune inhibitory receptor or ligand and/or b) an antibody to an immune stimulatory receptor or ligand.
  10. 10. A kit comprising the antibody of claim 1. 209 Date re�ue / Received date 2025-03-20

Description

DEMANDE OU BREVET VOLUMINEUX LA PRESENTE PARTIE DE CETTE DEMANDE OU CE BREVET COMPREND PLUS D'UN TOME. CECI EST LE TOME 1 DE 2 CONTENANT LES PAGES 1 A 188 NOTE : Pour les tomes additionels, veuillez contacter le Bureau canadien des brevets JillvIBO APPLICATIONS/PATENTS THIS SECTION OF THE APPLICATION/PATENT CONTAINS MORE THAN ONE VOLUME THIS IS VOLUME 1 OF 2 CONTAINING PAGES 1 TO 188 NOTE: For additional volumes, please contact the Canadian Patent Office NOM DU FICHIER / FILE NAME : NOTE POUR LE TOME / VOLUME NOTE: ANTI-ID.,A-G ANTIBODIES, COMPOSITIONS COMPRISING ANTI-HLA-G ANTIBODIES AND MEIBODS OF USING ANTI-ID.,A-G ANTIBODIES RELATED APPLICATION [0001] This application claims priority to U.S. provisional application number 62/737,666, filed filed September 27, 2018. FIELD [0002] Provided herein are antibodies with binding specificity for HLA-G and compositions comprising the antibodies, including pharmaceutical compositions, diagnostic compositions, and kits. Also provided are methods of using anti-HLA-G antibodies for therapeutic and diagnostic purposes. BACKGROUND [0003] HLA-G histocompatibility antigen, class I, G, also known as human leukocyte antigen G (HLA-G), is a protein that in humans is encoded by the HLA-Ggene. HLA-G belongs to the HLA nonclassical class I heavy chain paralogues. HLA-G is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). There are membrane bound and soluble forms of HLA-G. [0004] HLA-G is normally expressed at the maternal-fetal interface and other immune-privileged sites. HLA-G may play a role in immune tolerance in pregnancy, being expressed in the placenta by extravillous trophoblast cells, while the classical MHC class I genes (HLA-A and HLA-B) are not. As HLA-G was first identified in placenta samples, many studies have evaluated its role in pregnancy disorders, such as preeclampsia and recurrent pregnancy loss. See, Michita, Rafael Tomoyaet al., Human Immunology. 2016, 77 (10): 892-897. [0005] HLA-G has been shown to be immune-suppressive. By binding receptors expressed on various myeloid and lymphoid cells, HLA-G may directly inhibit the functions of NK cells, cytotoxic T-lymphocytes, B cells, neutrophils, monocytes, macrophages and dendritic cells. HLA-G also inhibits T and NK cell proliferation and cytolytic activities. HLA-G suppresses phagocytosis and induces the generation or expansion of regulatory T cells. -1 Date Rer;ue/Date Received 2024-05-22 PCT/0S2019/053158 [0006] HLA-G mediates immune function through at least three !TIM-containing inhibitory receptors, IL T2, IL T4, and KIR2DL4. On lymphoid and myeloid cells, for example, HLA-G mediates function through ILT2. On myeloid cells, HLA-G mediates function through ILT4. On decidual NK cells, HLA-G mediates immune function through KIR2DL4 and ILT2. [0007] HLA-G is an immune checkpoint target. HLA-G can directly inhibit immune cell function through receptor binding and/or trogocytosis and impairment of chemotaxis. HLA-G can lend tumor cells a higher invasive and metastatic potential. HLA-G promotes evasion of tumor immune surveillance, and enhances metastasis and the progression of malignancies. During tumor progression HLA-G has other effects, such as, inhibition of immune cell cytolysis, induction of immune cell apoptosis, and/or the generation of regulatory cells through receptor binding and/or trogocytosis. [0008] HLA-G expression is upregulated on a broad spectrum of tumors and is associated with poor prognosis and disease progression. Serum HLA-G levels are elevated in breast, lung, colorectal cancer (CRC), gastric, esophageal, neuroblastoma, cervical, and hematological cancers. HLA-G has also been found to be correlated with clinical parameters in advanced disease, such as, tumor metastasis, poor prognosis, immune escape, and tumor invasiveness. [0009] HLA-G is an attractive target for diseases, such as, for example, cancer. SUMMARY [0010] Provided herein are antibodies that selectively bind HLA-G. In some embodiments, the antibodies bind human HLA-G. In some embodiments, the antibodies comprise at least one CDR sequence defined by a consensus sequence provided in this disclosure. In some embodiments, the antibodies comprise one or more of an illustrative CDR, VH, or VL sequence provided in this disclosure, or a variant thereof. In some aspects, the variant is a variant with one or more conservative amino acid substitutions. [0011] Also provided are compositions and kits comprising the antibodies. In some embodiments, the compositions are pharmaceutical compositions. Any suitable pharmaceutical composition may be used. In some embodiments, the pharmaceutical composition is a composition for parenteral administration. [0012] This disclosure also provides methods of using the anti-HLA-G antibodies provided herein. In some embodiments, the method is a method of treatment. In some -2 PCT /0S2019/053158 embodiments, the method is an analytical method. In some embodiments, the m