Granted Patent
B2
US 12,365,719 · App. 17/742,189 · Granted Jul 22, 2025
CD80 extracellular domain polypeptides and their use in cancer treatment
Inventors:
Thomas Brennan (Thousand Oaks, CA); David Bellovin (Thousand Oaks, CA); Barbara Sennino (Thousand Oaks, CA); David Busha (Thousand Oaks, CA)
Assignee:
Five Prime Therapeutics, Inc.
C07K14/70532A61K38/1774A61K39/39558A61K45/06A61P1/00A61P35/00C07K16/00C07K16/2803C07K16/2818C07K16/2827A61K38/00A61K2039/505C07K2317/41C07K2319/03C07K2319/30
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Abstract
The present disclosure provides antibodies and antigen-binding fragments thereof that specifically bind to human B7-H4 (and optionally cynomolgus monkey, mouse, and/or rat B7-H4) and compositions comprising such antibodies or antigen-binding fragments thereof. In a specific aspect, the antibodies or antigen-binding fragments thereof that specifically bind to human B7-H4 increase T cell proliferation, increase interferon-gamma production, and/or deplete B7-H4 expressing cells via ADCC activity. The present disclosure also provides methods for treating disorders, such as cancer, by administering an antibody or antigen-binding fragment thereof that specifically binds to human B7-H4.
Claims (18)
1. A method of treating cancer in a subject, which comprises: administering to the subject a composition comprising a CD80 extracellular domain (ECD) fusion protein comprising the amino acid sequence of SEQ ID NO: 20 or SEQ ID NO: 21 and a pharmaceutically acceptable carrier.
2. The method of claim 1 , wherein the fusion protein is glycosylated.
3. The method of claim 2 , wherein said glycosylated fusion protein comprises sialic acid.
4. The method of claim 3 , wherein the glycosylated fusion protein comprises 15-30 moles of sialic acid (SA) per mole of fusion protein.
5. The method of claim 4 , wherein the glycosylated fusion protein comprises at least 20 moles of SA per mole of fusion protein.
6. The method of claim 1 , which further comprises: administering at least one immune stimulating agent to the subject in combination with said composition.
7. The method of claim 6 , wherein the at least one immune stimulating agent is an antagonist of a protein that inhibits T cell activation and/or an agonist of a protein that stimulates T cell activation.
8. The method of claim 7 , wherein the protein that inhibits T cell activation is CTLA4, LAG-3, TIM3, Galectin 9, CEACAM-1, BTLA, CD69, Galectin-1, TIGIT, CD113, GPR56, VISTA, B7-H3, B7-H4, 2B4, CD48, GARP, PD1H, LAIR1, TIM-1, TIM-4, or ILT4.
9. The method of claim 7 , wherein the protein that stimulates T cell activation is B7-2, CD28, 4-1BB (CD137), 4-1BBL, ICOS, ICOS-L, OX40, OX40L, GITR, GITRL, CD70, CD27, CD40, CD40L, DR3, or CD28H.
10. The method of claim 6 , wherein the at least one immune stimulating agent is a programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitor.
11. The method of claim 10 , wherein the PD-1/PD-L1 inhibitor comprises an anti-PD-1 antibody.
12. The method of claim 11 , wherein the anti-PD-1 antibody is nivolumab, pidilizumab, or pembrolizumab.
13. The method of claim 12 , wherein the anti-PD-1 antibody is pembrolizumab.
14. The method of claim 10 , wherein the PD-1/PD-L1 inhibitor comprises an anti-PD-L1 antibody.
15. The method of claim 1 , wherein the cancer is colon cancer, breast cancer, gastric cancer, non-small cell lung cancer, melanoma, squamous cell carcinoma of the head and neck, ovarian cancer, pancreatic cancer, renal cell carcinoma, hepatocellular carcinoma, bladder cancer, or endometrial cancer.
16. The method of claim 15 , wherein the cancer is colon cancer.
17. The method of claim 15 , wherein the cancer is melanoma.
18. The method of claim 6 , wherein the immune stimulating agent blocks endogenous CD80 binding to CTLA4.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jun 23, 2022
From: BRENNAN, THOMAS; BELLOVIN, DAVID; BUSHA, DAVID; SENNINO, BARBARA
To: FIVE PRIME THERAPEUTICS, INC.
Reel/Frame 060292/0739 →
Continuity (5)
Provisional Application
62373654
· Aug 11, 2016
Provisional Application
62249836
· Nov 2, 2015
References Cited (122)
US 4816397A
· Boss et al.
· 1989
[cited by applicant]
US 4816567A
· Cabilly et al.
· 1989
[cited by applicant]
US 5939598A
· Kucherlapati et al.
· 1999
[cited by applicant]
US 6030815A
· DeFrees
· 2000
[cited by examiner]
US 6503914B1
· Benish et al.
· 2003
[cited by applicant]
US 7294468B2
· Bell et al.
· 2007
[cited by applicant]
US 7932026B2
· Seshagiri
· 2011
[cited by applicant]
US 8293501B2
· Fredriksson et al.
· 2012
[cited by applicant]
US 8545849B2
· Borras et al.
· 2013
[cited by applicant]
US 20060141497A1
· Finkelstein
· 2006
[cited by applicant]
US 20090075267A1
· Siena et al.
· 2009
[cited by applicant]
US 20090202989A1
· Hillan
· 2009
[cited by applicant]
EP 0173494A2
· 1986
[cited by applicant]
EP 0171496B1
· 1993
[cited by applicant]
GB 2177096B
· 1989
[cited by applicant]
WO 2004111273A2
· 2004
[cited by applicant]
WO 2005118876A2
· 2005
[cited by applicant]
WO 2006107854A
· 2006
[cited by applicant]
WO 2006108627A1
· 2006
[cited by applicant]
WO 2007001868A1
· 2007
[cited by applicant]
WO 2007011702A2
· 2007
[cited by applicant]
WO 2007025044A2
· 2007
[cited by applicant]
WO WO2010027828A2
· 2010
[cited by examiner]
U.S. Appl. No. 62/387,486, Yie, J. et al.
[cited by applicant]
Allison, “Is personalized medicine finally arriving?” Nat. Biotech., 26: 509-517 (2008).
[cited by applicant]
Amado et al., “Analysis of KRAS mutations in patients with metastatic colorectal cancer receiving panitumumab monotherapy,” Eur. J. of Cancer Suppl., 5: 8 (2007).
[cited by applicant]
Amado et al, “Panitumumab (pmab) efficacy and patient-reported outcomes (PRO) in metastatic colorectal cancer (mCRC) patients (pts) with wild-type (WT) KRAS tumor status,” ASCO, Abstract No. 278 (2008).
[cited by applicant]
Amado et al., “Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer,” J. Clin. Oncol., 26:1626-1634 (2008).
[cited by applicant]
Amgen press release, “New biomarker data links KRAS gene to Vectibix™ clinical response,” Sep. 25, 2007. http://www.amgen.com/media/media_pr_detail.jsp?year=2007&releaseID=1055062.
[cited by applicant]
Amler et al., “Predicting clinical benefit in non-small-cell lung cancer patients treatedwith epidermal growth factor tyrosine kinase inhibitors,” Cold Spring Harbor Symp. Quant. Biol., 70: 483-488 (2005).
[cited by applicant]
Andreyev et al., “Kirsten ras mutations in patients with colorectal cancer: the ‘RASCAL II’ study,” Br. J. of Cane., 85: 692-696 (2001 ).
[cited by applicant]
Augello et al. “TP53 and p16INK4A, but not H-KI-Ras, are Involved in Tumorigenesis and Progression of Pleomorphic Adenomas”, J of Cellular Physiology, 207(3): 654-659, (Jun. 2006).
[cited by applicant]
Bardelli, “Terapie personalizzate per ii tumore del colon con analisi genomiche scoperte a Candiolo ea Niguarda,” OCGO, 4(1): 4-5 (2007), with English translation.
[cited by applicant]
Baselga et al., “Determinants of RASistance to anti-epidermal growth factor receptor agents,” J. Clin. Oncol., 26: 1582-1584 (2008).
[cited by applicant]
Bazan et al., “Specific codon 13 K-ras mutations are predictive of clinical outcome in colorectal cancer patients, whereas codon 12 K-ras mutations are associated with mucinous histotype,” Ann. Oncol., 13: 1438-1446 (20…
[cited by applicant]
Benvenuti et al., “Oncogenic activation of the RAS/RAF signaling pathway impairs the response of metastatic colorectal cancers to anti-epidermal growth factor receptor antibody therapies,” Cancer Res., 67: 2643-2648 (20…
[cited by applicant]
Bos et al., “Prevalence of ras gene mutations in human colorectal cancers,” Nature, 327:293-297 (1987).
[cited by applicant]
Braun et al., “Somatic activation of oncogenic Kras in hematopoietic cells initiates a rapidly fatal myeloproliferative disorder,” Proc. Natl. Acad. Sci., U.S.A., 101 (2): 597-602 (2004).
[cited by applicant]
W. Brugger et al., “Prospective Molecular Marker Analyses of EGFR and KRAS Froma Randomized, Placebo-Controlled Study of Erlotinib Maintenance Therapy in AdvancedNon-Small-Cell Lung Cancer,” J. Clin. Oncol., 29, publish…
[cited by applicant]
Buck, G. A. et al., Design Strategies and Performance of Custom DNA Sequencing Primers, BioTechniques, 27:528-536 (1999).
[cited by applicant]
Caraglia et al., “EGF-R small inhibitors and anti-EGF-R antibodies: advantages and limits of a new avenue in anticancer therapy,” Recent Patents on Anti-Cancer Drug Discovery, 1 :209-222 (2006).
[cited by applicant]
CenterWatch.com Pub (2006).
[cited by applicant]
Chua et al., “Panitumumab,” Drugs of Today, 42:711-719 (2006).
[cited by applicant]
Commu Oncology, 3:3-16, Oct. 2006.
[cited by applicant]
De Roock et al., “KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab,” Ann. Oncol., 19: 508-515 (2008), published online Nov. 1…
[cited by applicant]
W. De Roock et al., “Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis,” Lancet…
[cited by applicant]
Di Fiore et al., “Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy,” Br. J. Cancer, 96:1166-1169 (2007).
[cited by applicant]
F. Di Nicolantonio et al., “Wild-Type BRAF Is Required for Response to Panitumumab or Cetuximab in Metastatic Colorectal Cancer,” J. Clin. Oncol., 26(35):5705-5712 (2008).
[cited by applicant]
Eberhard et al., “Correlation of mutations in EGFR with clinical outcomes in NSCLC patients treated with erlotinib,” EJC Supplements, Proceedings of the 16th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Ther…
[cited by applicant]
Eberhard et al, “Mutations in the Epidermal Growth Factor Receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with…
[cited by applicant]
Eberhard et al., “Mutations in EGFR, HER2, KRAS, and BRAF in NSCLC: Prevalences and correlations with clinical outcomes in patients treated with carboplatin and paclitaxel with or without erlotinib,” Abstract No. 0-186,…
[cited by applicant]
Editorial, “Looking forward, looking back,” Nat. Biotech., 26: 475 (2008).
[cited by applicant]
S. Edkins et al., “Recurrent KRAS Codon 146 Mutations in Human Colorectal Cancer,” Cancer Biol. & Therapy, 5(8): 928-932 (2006).
[cited by applicant]
Esteller et al., “K-ras and p16 aberrations confer poor prognosis in human colorectal cancer,” J. Clin. Oncol., 19: 299-304 (2001 ).
[cited by applicant]
Ewert, S. et al., “Structure-based improvement of the biophysical properties of immunoglobulin VH domains with a generalizable approach,” Biochemistry, 42:1517-1528 (2003).
[cited by applicant]
Ewert, S. et al., “Biophysical properties of human antibody variable domains,” J. Mal. Biol., 325:531-553 (2003).
[cited by applicant]
Ford, C. F. et al., “Fusion tails for the recovery and purification of recombinant proteins,” Protein Expression and Purification, 2(2-3):95-107 (1991).
[cited by applicant]
Hecht et al., “Interim results from PACCE: Irinotecan (lri)/bevacizumab (bev) ± panitumumab (pmab) as first-line treatment (tx) for metastatic colorectal cancer (mCRC),” ASCO, Absract No. 279 (2008).
[cited by applicant]
Hecht et al., “Panitumumab (pmab) efficacy in patients (pts) with metastatic colorectalcancer (mCRC) with low or undetectable levels of epidermal growth factor receptor (EGFr): Final efficacy and KRAS analyses,” ASCO, A…
[cited by applicant]
Grussenmeyer, T. et al., “Complexes of polyoma virus medium T antigen and cellular proteins,” Proc. Natl. Acad. Sci. USA, 82:7952 (1985).
[cited by applicant]
Guo, Z. et al., “Structure-activity relationship for hydrophobic salts as viscosity-lowering excipients for concentrated solutions of monoclonal antibodies,” Pharm Res., 29:3102-3109 (2012).
[cited by applicant]
Honegger, A. et al., “Yet another numbering scheme for immunoglobulin variable domains: an automatic modeling and analysis tool,” J. Mal. Biol., 309:657-670 (2001).
[cited by applicant]
Hopp, T. P. et al., A Short Polypeptide Marker Sequence Useful for Recombinant Protein Identification and Purification, Nature Biotechnology, 6:1204-1210 (1988).
[cited by applicant]
Horton, J. D., Cohen, J.C. & Hobbs, H. H., “Molecular Biology of PCSK9: Its Role in LDL Metabolism,” Trends Biochem. Sci., 32(2):71-77. doi:10.1016/j .tibs.2006.12.008, Seidah & Prat (2007).
[cited by applicant]
Jackson, S. et al., “The Crystal Structure of PCSK9: a Regulator of Plasma LDL-Cholesterol,” Structure, 15:545-552 (2007).
[cited by applicant]
Jefferis, R. and Lefranc, M-P., Human immunoglobulin allotypes: possible implications for immunogenicity, mAbs, 1:332-338 (2009).
[cited by applicant]
Kabat, E. A. et al., “Sequences of Proteins of Immunological Interest”, Fifth Edition, Public Health Service, National Institutes of Health, Bethesda, MD, Publication No. 91-3242 (1991) (Table of Contents Only).
[cited by applicant]
Kanai, S. et al., “Reversible self-association of a concentrated monoclonal antibody solution mediated by Fab-Fab interaction that impacts solution viscosity,” Journal of Pharmacuetical Sciences, 97(10):4219-4227 (2008).
[cited by applicant]
Ketchem, R. R. et al., “Mitigation of monoclonal antibody viscosity by modification of protein surface charge,” Abstracts of Papers; ACS National Meeting & Exposition, American Chemical Society, US, 243
[cited by applicant]
P. Laurent-Puig et al., “Analysis of PTEN, BRAF, and EGFR Status in Determining Benefit From Cetuximab Therapy in Wild-Type KRAS Metastatic Colon Cancer,” J. Clin. Oncol., 27(35): 5924-5930 (2009).
[cited by applicant]
Lemaigre, F. P. et al., “Transcriptional control of genes that regulate glycolysis and gluconeogenesis in adult liver” Biochem. J. 303:1-14 (1994).
[cited by applicant]
Li, L. et al., “Concentration dependent viscosity of monoclonal antibody solutions: explaining experimental behavior in terms of molecular properties,” Pharm. Res., 31:3161-3178 (2014).
[cited by applicant]
Lievre et al., “KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer,” Cancer Res., 66: 3992-3995 (2006).
[cited by applicant]
Lievre et al., “KRAS mutations in colorectal cancer is a predictive factor of response and progression free survival in patients treated with Cetuximab,” Abstract 5671, AACR Proceedings (2007).
[cited by applicant]
Lievre et al., “KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab,” J. Clin. Oneal., 26: 374-379 (2008).
[cited by applicant]
Loeken, M. R., “Effects of mutation of the CREB binding site of the somatostatin promoter on cyclic AMP responsiveness in CV-1 cells,”
[cited by applicant]
Malik et al., J Clin Onco ASCO Meeting Abstract, vol. 23 #3520, Jun. 2005.
[cited by applicant]
Malumbres et al., “RAS oncogenes: the first 30 years,” Nat. Rev., 3: 7-13 (2003).
[cited by applicant]
C. Mao et al., “BRAFV600E mutation and resistance to anti-EGFR monoclonal antibodies in patients with metastatic colorectal cancer: a meta-analysis,” Mot. Biol. Rep.,38: 2219-2223 (2011 ).
[cited by applicant]
McGehee, R. E. et al., “Differentiation-specific element: a cis-acting developmental switch required for the sustained transcriptional expression of the angiotensinogen gene during hormonal-induced differentiation of 3T…
[cited by applicant]
Moroni et al., “Gene copy of number for epidermal growth factor receptor (EGFR) and clinical response to antiEGFR treatment in colorectal cancer: a cohort study,” Lancet Oneal., 6: 279-286 (2005).
[cited by applicant]
Moroni et al. “Somatic mutation of EGFR catalytic domain and treatment with gefitinibin colorectal cancer,” Ann. One., 16: 1848-1849 (2005).
[cited by applicant]
Moroni et al., “EGFR Fish in colorectal cancer: what is the current reality?” LancetOneal., 9: 402-403 (2008).
[cited by applicant]
Morrison, S. L. et al., “Chimeric human antibody molecules: mouse antigen-binding domains with human constant region domains,”
[cited by applicant]
Mukohara et al., “Differential Effects of Gefitinib and Cetuximab on Non-small-cell Lung Cancers Bearing Epidermal Growth Factor Receptor Mutations”
[cited by applicant]
Neergaard, M. S. et al., “Viscosity of high concentration protein formulations of monoclonal antibodies of IgGI and IgG4 subclass—prediction of viscosity through protein-protein interaction measurements”
[cited by applicant]
Nilsson, B. et al., “Expression and purification of recombinant insulin-like growth factorsfrom
[cited by applicant]
Nilsson, B. et al., “Immobilization and purification of enzymes with staphylococcal protein A gene fusion vectors,”
[cited by applicant]
O'Reilly, M. A. et al., “Identification of an activating transcription factor (ATF) binding site in the human transforming growth factor-132 promoter,”
[cited by applicant]
Pao et al., “KRAS mutations and primary resistance of lung adenocarcinomas to gefitinibor erlotinib,” PLOS Medicine, 2:57-61 (2005).
[cited by applicant]
Paul, W., ed., Fundamental Immunology, Chapter 7, 2
[cited by applicant]
PCT Invitation to Pay Additional Fees and Annex to Form PCT/ISA/206, Communication Relating to the Results of the Partial International Search, received in PCT International Application No. PCT/US2008/003327, faxed Sep.…
[cited by applicant]
Products—KRAS status predicts non-response to Amgen's Vectibix in metastaticcolorectal cancer, www.scriQnews.com, 3300: 18-19 (2007).
[cited by applicant]
Porges et al., “DNA, AMGN, Merck KGaA: Could KRAS save Vectibix? Could it impact Avastin? Chasing the genomic breakthrough,” Bernstein Research, Oct. 8, 2007.
[cited by applicant]
M. Raponi et al., “KRAS mutations predict response to EGFR inhibitors,” Curr. Opin. Pharmacol., 8: 413-418 (2008).
[cited by applicant]
P. Roberts et al., “Personalized Medicine in Non-Small-Cell Lung Cancer: Is KRAS a Useful Marker in Selecting Patients for Epidermal Growth Factor Receptor-Targeted Therapy?,” J. Clin. Oncol., 28(31): 4769-4777 (2010).
[cited by applicant]
Ropartz, C., Schanfield, M. S., Steinberg, A.G., “Review of the notation for the allotypic and related markers of human immunoglobulins,” WHO meeting on human immunoglobulin allotypic markers, Held Jul. 16-19, 1974, Rau…
[cited by applicant]
Rothlisberger, D. et al., “Domain interactions in the Fab fragment: a comparative evaluation of the single-chain Fv and Fab format engineered with variable domains of different stability,”
[cited by applicant]
Santos et al., “Malignant activation of a K-ras oncogene in lung carcinoma but not in normal tissue of the same patient,” Science, 223: 661-664 (1984).
[cited by applicant]
Sartore-Bianchi et al., “Anti-EGFR monoclonal antibodies in the treatment of non-small cell lung cancer,” Ann. One., 17(suppl. 2): ii49-ii51 (2006).
[cited by applicant]
Sartore-Bianchi et al., “Epidermal growth factor receptor gene copy number and clinical outcome of metastatic colorectal cancer treated with panitumumab,” J. Clin. Oneal., 25: 3238-3245 (2007).
[cited by applicant]
Seidah, N. G. & Prat, A., “The proprotein convertases are potential targets in the treatment of dyslipidemia,”
[cited by applicant]
Shukla, A. A. et al., “Downstream processing of monoclonal antibodie-Application of platform approaches,”
[cited by applicant]
Singh, S. N. et al., “Dipole-Dipole Interaction in Antibody Solutions: Correlation with Viscosity Behavior at High Concentrations,”
[cited by applicant]
Smith, D. B. et al., “Single-step purification of polypeptides expressed in
[cited by applicant]
Takeda, S. et al., “Construction of chimaeric processed immunoglobulin genes containing mouse variable and human constant region sequences,”
[cited by applicant]
Tomlinson, I. M. et al., “The structural repertoire of the human V kappa domain,”
[cited by applicant]
Treisman, R. The SRE: a growth factor response transcriptional regulator, “
[cited by applicant]
Tseng, C. C. et al., “Postprandial stimulation of insulin release by glucose-dependent insulinotropic polypeptide (GIP). Effect of a specific glucose-dependent insulinotropic polypeptide receptor antagonist in the rat,”
[cited by applicant]
Van Den Bremer, E.T.J. et al., “Human IgG is produced in a pro-form that requires clipping of C-terminal lysines for maximal complement activation,”
[cited by applicant]
Vidarsson, G. et al., “IgG subclasses and allotypes: from structure to effector functions,”
[cited by applicant]
Yadav, S. et al., “The influence of charge distribution on self-association and viscosity behavior of monoclonal antibody solutions,”
[cited by applicant]
Yadav, S. et al., “Viscosity behavior of high-concentration monoclonal antibody solutions: correlation with interaction parameter and electroviscous effects,”
[cited by applicant]
Yadav, S. et al., “Establishing a Link Between Amino Acid Sequences and Self-Associating Viscoelastic Behavior of Two Closely Related Monoclonal Antibodies,” Pharm. Res., 28(7):1750-1764 (2011).
[cited by applicant]
Ye, J. et al., “Characterization of a Silencer Regulatory Element in the Human Interferon-y Promoter,”
[cited by applicant]
Cited By (1)