IP Library › Granted Patent US 12,528,864
Granted Patent B2
US 12,528,864 · App. 17/902,305 · Granted Jan 20, 2026

Antigen binding proteins

Inventors: Yan Y. Degenhardt (Collegeville, PA); Jun Guan (Collegeville, PA); Kenneth William Hance (Collegeville, PA); Peter Joseph Morley (Stevenage, GB)
Assignee: GlaxoSmithKline Intellectual Property Development Limited
C07K16/2803A61P35/00A61K2039/505C07K2317/21C07K2317/24C07K2317/76C07K2317/77C07K2317/92
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,528,864
App. No.
17/902,305
Granted
Jan 20, 2026
Kind
B2
Abstract

The present disclosure relates to compositions for treating CD96 mediated diseases, and related methods.

Claims (44)

1 . A method for the treatment of a cancer in a human patient having the cancer, wherein the method comprises administering to the human patient a therapeutically effective amount of an antibody or an antigen binding fragment thereof that specifically binds to CD96, wherein the antibody or the antigen binding fragment thereof comprises:

CDRH1 of SEQ ID NO: 115;

CDRH2 of SEQ ID NO: 145;

CDRH3 of SEQ ID NO: 147;

CDRL1 of SEQ ID NO: 97;

CDRL2 of SEQ ID NO: 99; and

CDRL3 of SEQ ID NO: 101.

2 . The method according to claim 1 , wherein the cancer is liver cancer, ovarian cancer, non-small cell lung cancer (NSCLC), renal cancer, colon cancer, colorectal cancer, bladder cancer, or head and neck squamous-cell carcinoma (HNSCC).

3 . The method according to claim 1 , wherein the cancer is non-small cell lung cancer (NSCLC).

4 . The method according to claim 1 , wherein the antibody or the antigen binding fragment thereof comprises:

a VH region that is at least 90% identical to SEQ ID NO: 86; and

a VL region that is at least 90% identical to SEQ ID NO: 85.

5 . The method according to claim 1 , wherein the antibody or the antigen binding fragment thereof comprises:

a VH region that is 100% identical to SEQ ID NO: 86; and

a VL region that is 100% identical to SEQ ID NO: 85.

6 . The method according to claim 1 , wherein the antibody or the antigen binding fragment thereof comprises a humanized sequence or a chimeric sequence.

7 . The method according to claim 1 , wherein the antibody or the antigen binding fragment thereof is a monoclonal antibody.

8 . The method according to claim 5 , wherein the antibody or the antigen binding fragment thereof is a monoclonal antibody.

9 . The method according to claim 7 , wherein the antibody further comprises a human wild-type IgG1 Fc domain.

10 . The method according to claim 8 , wherein the antibody further comprises a human wild-type IgG1 Fc domain.

11 . A method for the treatment of a cancer in a human patient having the cancer, wherein the method comprises administering to the human patient a therapeutically effective amount of a pharmaceutical composition comprising an antibody or an antigen binding fragment thereof that specifically binds to CD96, and a pharmaceutically acceptable excipient, wherein the antibody or the antigen binding fragment thereof comprises:

CDRH1 of SEQ ID NO: 115;

CDRH2 of SEQ ID NO: 145;

CDRH3 of SEQ ID NO: 147;

CDRL1 of SEQ ID NO: 97;

CDRL2 of SEQ ID NO: 99; and

CDRL3 of SEQ ID NO: 101.

12 . The method according to claim 11 , wherein the antibody or the antigen binding fragment thereof comprises:

a VH region that is at least 90% identical to SEQ ID NO: 86; and

a VL region that is at least 90% identical to SEQ ID NO: 85.

13 . The method according to claim 11 , wherein the antibody or the antigen binding fragment thereof comprises:

a VH region that is 100% identical to SEQ ID NO: 86; and

a VL region that is 100% identical to SEQ ID NO: 85.

14 . The method according to claim 11 , wherein the antibody or the antigen binding fragment thereof comprises a humanized sequence or a chimeric sequence.

15 . The method according to claim 11 , wherein the antibody or the antigen binding fragment thereof is a monoclonal antibody.

16 . The method according to claim 13 , wherein the antibody or the antigen binding fragment thereof is a monoclonal antibody.

17 . The method according to claim 15 , wherein the antibody further comprises a human wild-type IgG1 Fc domain.

18 . The method according to claim 16 , wherein the antibody further comprises a human wild-type IgG1 Fc domain.

19 . The method according to claim 10 , wherein the antibody comprises:

a full length heavy chain amino acid sequence of SEQ ID NO: 165; and

a full length light chain amino acid sequence of SEQ ID NO: 166.

20 . The method according to claim 18 , wherein the antibody comprises:

a full length heavy chain amino acid sequence of SEQ ID NO: 165; and

a full length light chain amino acid sequence of SEQ ID NO: 166.

Assignments (2)
CHANGE OF ADDRESS Recorded Oct 8, 2025
From: GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED
To: GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED
Reel/Frame 073032/0390 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 20, 2022
From: DEGENHARDT, YAN Y.; GUAN, JUN; HANCE, KENNETH WILLIAM; MORLEY, PETER JOSEPH
To: GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED
Reel/Frame 061482/0057 →
Continuity (5)
Division 17530849 · Nov 19, 2021
Continuation PCTEP2020076834 · Sep 25, 2020
Provisional Application 63057508 · Jul 28, 2020
Provisional Application 62906876 · Sep 27, 2019
Related Publication 20230279106A1 · Sep 7, 2023
References Cited (50)
WO 2008073316A2 · 2008 [cited by applicant]
WO 2009126688A2 · 2009 [cited by applicant]
WO 2014089169A2 · 2014 [cited by applicant]
WO 2015009856A2 · 2015 [cited by applicant]
WO 2015024060A1 · 2015 [cited by applicant]
WO 2019030377A1 · 2019 [cited by applicant]
WO 2019091449A1 · 2019 [cited by applicant]
WO 2020132034A1 · 2020 [cited by applicant]
WO 2021042019A1 · 2021 [cited by applicant]
WO 2021058711A2 · 2021 [cited by applicant]
Mittal et al. (Cancer Immunol. Res. Apr. 2019; 7 (4): 559-71). [cited by examiner]
Chen “Enhancement and destruction of antibody function by somatic mutation: unequal occurrence is controlled by V gene combinatorial associations” EMBO 14(12):2784-2794 (Year: 1995). [cited by examiner]
Kussie “A Single Engineered Amino Acid Substitution Changes Antibody Fine Specificity” J immunol 152(1):146-52 (Year: 1994). [cited by examiner]
PCT/EP2020/076834 International Search Report and Written Opinion, dated May 4, 2021. [cited by applicant]
Aguilera, A. et al., CD96 targeted antibodies need not block CD96-CD155 interactions to promote NK cell anti-metastatic activity. Oncoimmunology 7, e1424677, doi:10.1080/2162402X.2018.1424677 (2018). [cited by applicant]
Blake. et al.,“Molecular Pathways: Targeting CD96 and TIGIT for Cancer Immunotherapy”, Clinical Cancer Research, 22(21):5183-5188 (2016). [cited by applicant]
Blake. et al., “Suppression of Metastases Using New Lymphocyte Checkpoint Target for Cancer Immunotherapy”, Cancer Discovery, 6(4): 446-459 (2016). [cited by applicant]
Brooks, J. et al. Perioperative, Spatiotemporally Coordinated Activation of T and NK Cells Prevents Recurrence of Pancreatic Cancer. Cancer Res 78, 475-488, doi:10.1158/0008-5472.CAN-17-2415 (2018). [cited by applicant]
Chan, et al., “Receptors that interact with nectin and nectin-like proteins in the immunosurveillance and immunotherapy of cancer,” Curr Opin Immunol., 24(2):246-51 (2012). [cited by applicant]
Chan, et al., “The receptors CD96 and CD226 oppose each other in the regulation of natural killer cell functions,” Nature Immunology, 15(5): 431-438 (2014). [cited by applicant]
Chiang, et al., “CD96 functions as a co-stimulatory receptor to enhance CD8+ T cell activation and effector responses,” Eur. J. Immunol., 50: 891-902 (2020). [cited by applicant]
Cluxton, C. D. et al. Suppression of Natural Killer cell NKG2D and CD226 anti-tumour cascades by platelet cloaked cancer cells: Implications for the metastatic cascade. PLoS One 14, e0211538, doi:10.1371/journal.pone.02… [cited by applicant]
Ellis et al. “Interactions of CD80 and CD86 with CD28 and CTLA4.” J. Immunol. 156 (8): 2700-2709 (1996). [cited by applicant]
Eriksson, et al., “Differential expression of CD96 surface molecule represents CD8+ T cells with dissimilar effector function during HIV-1 infection,” Plos One, (2012). [cited by applicant]
Fuchs, “The role of NK cell recognition of nectin and nectin-like proteins in tumor immunosurveillance,” Seminars in Cancer Bioloiy, 16(5): 359-366 (2006). [cited by applicant]
Fuchs, et al., “Cutting Edge: CD96 (Tactile) Promotes NK Cell-Target Cell Adhesion by Interacting with the Poliovirus receptor (CD155),” J. Immunol., 172(7): 3994-3998 (2004). [cited by applicant]
Georgiev, et al., “Coming of Age: CD96 Emerges as Modulator of Immune Responses,” Frontiers in Immunology, 9:1072 (2018). [cited by applicant]
Gong, J. et al. Establishment of an enzyme-linked immunosorbent assay system for determining soluble CD96 and its application in the measurement of sCD96 in patients with viral hepatitis B and hepatic cirrhosis. Clin Ex… [cited by applicant]
Gramatzki, et al., “Antibodies TC-12 (“unique”) and TH-111 (CD96) characterize T-cell acute lymphoblastic eukemia and a subgroup of acute myeloid leukemia,” Exp Hematol., 13:1209-14 (1998). [cited by applicant]
Harjunpaa, H. et al. Deficiency of host CD96 and PD-1 or TIGIT enhances tumor immunity without significantly compromising immune homeostasis. Oncoimmunology 7(7), e1445949, doi:10.1080/2162402X.2018.1445949 (2018). [cited by applicant]
Holmes et al. “Structural consequences of humanizing an antibody.” J. Immunol. 158(5):2192-2201 (1997). [cited by applicant]
Hosen, N. et al. CD96 is a leukemic stem cell-specific marker in human acute myeloid leukemia. Proc Natl Acad Sci US A 104, 11008-11013, doi:10.1073/pnas.0704271104 (2007). [cited by applicant]
Jin, et al., “Hitting the complexity of the TIGIT-CD96-CD112R-CD226 axis for next-generation cancer immunotherapy,” BMB Reports, 54(1):2-11 (2021). [cited by applicant]
Kirchgessner, H. et al. The transmembrane adaptor protein TRIM regulates T cell receptor (TCR) expression and TCR-mediated signaling via an association with the TCR zeta chain. J Exp Med 193, 1269-1284, doi:10.1084/iem.… [cited by applicant]
Lepletier, A. et al. The immune checkpoint CD96 defines a distinct lymphocyte phenotype and is highly expressed on tumor-infiltrating T cells. Immunol Cell Biol 97, 152-164, doi:10.1111/imcb.12205 (2019). [cited by applicant]
Maier, et al., “The adhesion receptor CD155 determines the magnitude of humoral immune responses against orally Ingested antigens,” Eur. J. Immunol., 37:2214-2225 (2007). [cited by applicant]
Martinet, et al., “Balancing natural killer cell activation through paired receptors,” Nature Reviews Immunology, 15:243 (2015). [cited by applicant]
Melsen, J.E. et al. Human Bone Marrow-Resident Natural Killer Cells Have a Unique Transcriptional Profile and Resemble Resident Memory CD8(+) T Cells. Front Immunol 9, 1829, doi:10.3389/fimmu.2018.01829 (2018). [cited by applicant]
Meyer, et al., “CD96 interaction with CD155 via its first Ig-like domain is modulated by alternative splicing or mutations in distal Ig-like domains,” Journal of Biol. Chem., 284(4):2235-2244 (2009). [cited by applicant]
Mittal, et al., “CD96 is an Immune Checkpoint that Regulates CD8+ T-cell Antitumor function,” Cancer Immunology Research, 7(4):559-571 (2019). [cited by applicant]
Nodehi, et al., “Enhanced ADCC activity of affinity matured and Fe-engineered mini-antibodies directed against the AML stem cell antigen CD96,” PLoS One, 7(8) e42426 (2012). [cited by applicant]
Rudd, C. E. & Schneider, H. Unifying concepts in CD28, ICOS and CTLA4 co-receptor signalling. Nat Rev Immunol 3, 544-556, doi:10.1038/nril 131 (2003). [cited by applicant]
Seth, et al., “The murine pan T cell marker CD96 is an adhesion receptor for CD155 and nectin-1,” Biochem Biophys Res Comm, 364, 959-965 (2007). [cited by applicant]
Stanietsky, “Paired NK cell receptors controlling NK cytotoxicity.” FEBS Letters, 584(24):4895-4900 (2010). [cited by applicant]
Sun, H. et al. Accumulation of Tumor-Infiltrating CD49a(+) NK Cells Correlates with Poor Prognosis for Human Hepatocellular Carcinoma. Cancer Immunol Res 7, 1535-1546, doi:10.1158/2326-6066.CIR-18-0757 (2019). [cited by applicant]
Sun, H. et al. Human CD96 Correlates to Natural Killer Cell Exhaustion and Predicts the Prognosis of Human Hepatocellular Carcinoma. Hepatology 70, 168-183, doi:10.1002/hep.30347 (2019). [cited by applicant]
Van Den Beucken et al. “Building novel binding ligands to B7.1 and B7.2 based on human antibody single variable light chain domains.” J. Mol. Biol., 310(3):591-601 (2001). [cited by applicant]
Wang, et al., “Identification and molecular cloning of tactile. A novel human T cell activation antigen that is a member of the Ig gene superfamily,” J. Immunology, 148(8), 2600-2608 (1992). [cited by applicant]
Wu, M., Mei, F., Liu, W. & Jiang, J. Comprehensive characterization of tumor infiltrating natural killer cells and clinical significance in hepatocellular +C105:E107carcinoma based on gene expression profiles. Biomed Ph… [cited by applicant]
Zhang, W. et al. Expressions of CD96 and CD123 in Bone Marrow Cells of Patients with Myelodysplastic Syndromes. Clin Lab 61, 1429-1434, doi:10.7754/clin.lab.2015.141240 (2015). [cited by applicant]