IP Library › Granted Patent US 12,252,550
Granted Patent B2
US 12,252,550 · App. 17/749,362 · Granted Mar 18, 2025

Antibodies that bind to C1S and uses thereof

Inventor: Vahe Bedian (Waltham, MA)
Assignee: DIANTHUS THERAPEUTICS OPCO, INC.
C07K16/40A61P7/00A61K2039/505C07K16/18C07K2317/24C07K2317/76
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Quick Facts
Patent No.
US 12,252,550
App. No.
17/749,362
Granted
Mar 18, 2025
Kind
B2
Abstract

Embodiments that are provided for herein relate to antibodies and compositions that bind to C1s. Also provided are methods of producing the antibodies of the present disclosure, as well as uses of the provided antibodies and compositions for the treatment of C1s mediated diseases and disorders.

Claims (29)

1. An antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a HCDR1, a HCDR2, and a HCDR3; and the light chain variable region comprises a LCDR1, a LCDR2, and a LCRD3, and wherein:

the HCDR1 comprises the amino acid sequence of SEQ ID NO: 32;

the HCDR2 comprises the amino acid sequence of SEQ ID NO: 33;

the HCDR3 comprises the amino acid sequence of SEQ ID NO: 17;

the LCDR1 comprises the amino acid sequence of SEQ ID NO: 34;

the LCDR2 comprises the amino acid sequence of SEQ ID NO: 35; and

the LCDR3 comprises the amino acid sequence of SEQ ID NO: 36.

2. The antibody, or antigen-binding fragment thereof, of claim 1 , wherein the antibody, or antigen binding fragment thereof, comprises the heavy chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 3 and the light chain variable region comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 4.

3. The antibody, or antigen-binding fragment thereof, of claim 2 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 3 and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 4.

4. The antibody, or antigen binding fragment thereof, of claim 2 , wherein the heavy chain variable region is linked to a constant region comprising the amino acid sequence selected from the group consisting of SEQ ID NO: 7, 8, 57, and 58.

5. The antibody, or antigen binding fragment thereof, of claim 4 , wherein the constant region comprises the amino acid sequence of SEQ ID NO: 8.

6. The antibody, or antigen binding fragment thereof, of claim 4 , wherein the constant region comprises the amino acid sequence of SEQ ID NO: 58.

7. The antibody, or antigen binding fragment thereof, of claim 2 , wherein the light chain variable region is linked to a constant domain comprising the amino acid sequence of SEQ ID NO: 65.

8. The antibody, or antigen binding fragment thereof, of claim 2 , wherein the antibody, or antigen binding fragment thereof, comprises:

a heavy chain comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 68 or the amino acid sequence of SEQ ID NO: 69; and

a light chain comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 73.

9. The antibody, or antigen binding fragment thereof, of claim 2 , wherein the antibody, or antigen binding fragment thereof, comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 69 and a light chain comprising the amino acid sequence of SEQ ID NO: 73.

10. The antibody, or antigen binding fragment thereof, of claim 2 , wherein the antibody, or antigen binding fragment thereof, comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 68 and a light chain comprising the amino acid sequence of SEQ ID NO: 73.

11. A pharmaceutical composition comprising an antibody, or antigen binding fragment thereof, of claim 4 .

12. A pharmaceutical composition comprising an antibody, or antigen binding fragment thereof, of claim 7 .

13. A pharmaceutical composition comprising an antibody, or antigen binding fragment thereof, of claim 1 .

14. A pharmaceutical composition comprising an antibody, or antigen binding fragment thereof, of claim 2 .

15. A pharmaceutical composition comprising an antibody, or antigen binding fragment thereof, of claim 3 .

16. A method of treating a subject with Myasthenia Gravis, hemolysis, Cold Agglutinin Disease, Immune Thrombocytopenia (ITP), Glomerulopaties, Atypical Hemolytic uremic syndrome, antiphospholipid antibody syndrome, or transplant rejection, the method comprising administering to the subject an antibody, or antigen binding fragment thereof, of claim 2 .

17. A method of treating a subject with Myasthenia Gravis, hemolysis, Cold Agglutinin Disease, Immune Thrombocytopenia (ITP), Glomerulopaties, Atypical Hemolytic uremic syndrome, antiphospholipid antibody syndrome, or transplant rejection, the method comprising administering to the subject an antibody, or antigen binding fragment thereof, of claim 1 .

18. A method of treating a subject with Myasthenia Gravis, hemolysis, Cold Agglutinin Disease, Immune Thrombocytopenia (ITP), Glomerulopaties, Atypical Hemolytic uremic syndrome, antiphospholipid antibody syndrome, or transplant rejection, the method comprising administering to the subject an antibody, or antigen binding fragment thereof, of claim 3 .

19. A method of treating a subject with Myasthenia Gravis, hemolysis, Cold Agglutinin Disease, Immune Thrombocytopenia (ITP), Glomerulopaties, Atypical Hemolytic uremic syndrome, antiphospholipid antibody syndrome, or transplant rejection, the method comprising administering to the subject an antibody, or antigen binding fragment thereof, of claim 8 .

20. A method of treating a subject with Myasthenia Gravis, hemolysis, Cold Agglutinin Disease, Immune Thrombocytopenia (ITP), Glomerulopaties, Atypical Hemolytic uremic syndrome, antiphospholipid antibody syndrome, or transplant rejection, the method comprising administering to the subject an antibody, or antigen binding fragment thereof, of claim 9 .

21. A method of treating a subject with Myasthenia Gravis, hemolysis, Cold Agglutinin Disease, Immune Thrombocytopenia (ITP), Glomerulopaties, Atypical Hemolytic uremic syndrome, antiphospholipid antibody syndrome, or transplant rejection, the method comprising administering to the subject an antibody, or antigen binding fragment thereof, of claim 10 .

Assignments (2)
CHANGE OF NAME Recorded Nov 17, 2023
From: DIANTHUS THERAPEUTICS, INC.
To: DIANTHUS THERAPEUTICS OPCO, INC.
Reel/Frame 065625/0677 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 28, 2022
From: BEDIAN, VAHE
To: DIANTHUS THERAPEUTICS, INC.
Reel/Frame 060653/0379 →
Continuity (2)
Provisional Application 63201952 · May 20, 2021
Related Publication 20220380483A1 · Dec 1, 2022
References Cited (98)
US 4439196A · Higuchi · 1984 [cited by applicant]
US 4447224A · DeCant, Jr. et al. · 1984 [cited by applicant]
US 4447233A · Mayfield · 1984 [cited by applicant]
US 4487603A · Harris · 1984 [cited by applicant]
US 4596556A · Morrow et al. · 1986 [cited by applicant]
US 4790824A · Morrow et al. · 1988 [cited by applicant]
US 4816567A · Cabilly et al. · 1989 [cited by applicant]
US 4941880A · Burns · 1990 [cited by applicant]
US 4946778A · Ladner et al. · 1990 [cited by applicant]
US 5064413A · McKinnon et al. · 1991 [cited by applicant]
US 5260203A · Adner et al. · 1993 [cited by applicant]
US 5312335A · McKinnon et al. · 1994 [cited by applicant]
US 5383851A · McKinnon, Jr. et al. · 1995 [cited by applicant]
US 5399163A · Peterson et al. · 1995 [cited by applicant]
US 6005079A · Casterman et al. · 1999 [cited by applicant]
US 6096002A · Landau · 2000 [cited by applicant]
US 6620135B1 · Weston et al. · 2003 [cited by applicant]
US 7670600B2 · Dall'Acqua et al. · 2010 [cited by applicant]
US 8394925B2 · Chamberlain et al. · 2013 [cited by applicant]
US 20150133317A1 · Robinson · 2015 [cited by examiner]
US 20160053002A1 · Van Vlasselaer et al. · 2016 [cited by applicant]
US 20160090425A1 · Rosenthal et al. · 2016 [cited by applicant]
US 20160215065A1 · Lin · 2016 [cited by examiner]
US 20190010233A1 · Liu et al. · 2019 [cited by applicant]
US 20200048332A1 · Panicker et al. · 2020 [cited by applicant]
US 20210115116A1 · Van Vlasselaer et al. · 2021 [cited by applicant]
EP 0404097A2 · 1990 [cited by applicant]
WO 1988001649A1 · 1988 [cited by applicant]
WO 1993011161A1 · 1993 [cited by applicant]
WO 1994004678A1 · 1994 [cited by applicant]
WO 1994025591A1 · 1994 [cited by applicant]
WO 2012148497A2 · 2012 [cited by applicant]
WO 2015054670A1 · 2015 [cited by applicant]
WO 2018071676A1 · 2018 [cited by applicant]
WO 2018091661A1 · 2018 [cited by applicant]
WO 2022046888A1 · 2022 [cited by applicant]
Fernandez-Quintero, M.-L., et al., Germline-Dependent Antibody Paratope States and Pairing Specific VH-VL Interface Dynamics, Aug. 2021, Frontiers, 12, 675655 (Year: 2021). [cited by examiner]
Rabia, L., et al Understanding and overcoming trade-offs between antibody affinity, specificity, stability, and solubility, 2018, Elsevier, 15(137); 365-374 (Year: 2018). [cited by examiner]
Alegre et al., “Effect of a Single Amino Acid Mutation on the Activating and Immunosuppressive Properties of a “Humanized” OKT3 Monoclonal Antibody,” J Immunol, 148(1):3461-3468 (1992). [cited by applicant]
Baert et al., “Influence of Immunogenicity on the Long-Term Efficacy of Infliximab in Crohn's Disease,” (2003) New Engl. J. Med. 348:601-608. [cited by applicant]
Beniaminovitz et al., “Prevention of Rejection in Cardiac Transplantation by Blockade of the Interleukin-2 Receptor with a Monoclonal Antibody,” (2000) New Engl. J. Med. 342(9):613-619. [cited by applicant]
Brown et al., “The Classical Pathway is the Dominant Complement Pathway Required for Innate Immunity to [cited by applicant]
Budayova-Spano et al., “The Crystal Structure of the Zymogen Catalytic Domain of Complement Protease C1r Reveals that a Disruptive Mechanical Stress is Required to Trigger Activation of the C1 Complex,” EMBO J. (2002) 2… [cited by applicant]
Chothia et al., “Canonical Structures for the Hypervariable Regions of Immunoglobulins,” (1987) J. Mol. Biol. 196:901-917. [cited by applicant]
Chothia et al., “Conformations of Immunoglobulin Hypervariable Regions,” (1989) Nature 342: 877-883. [cited by applicant]
Clackson et al., “Making Antibody Fragments Using Phage Display Libraries,” (1991) Nature 352:624-628. (Abstract Only). [cited by applicant]
Dall'Acqua et al., “Increasing the Affinity of a Human IgG1 for the Neonatal Fc Receptor: Biological Consequences,” J Immunol, 169(9): 5171-5180 (2002). [cited by applicant]
David et al., “Protein Iodination with Solid State Lactoperoxidase,” (1974) Biochemistry 13(5): 1014-1021. (Abstract Only). [cited by applicant]
Dombrowski et al., “Direct Submission,” Marine Science Institute (Feb. 9, 2016) pp. 1-2. [cited by applicant]
Ghosh et al., “Natalizumab for Active Crohn's Disease,” (2003) New Engl. J. Med. 348:24-32. [cited by applicant]
Herold et al., “Anti-CD3 Monoclonal Antibody in New-Onset Type 1 Diabetes Mellitus,” (2002) New Engl. J. Med. 346(22): 1692-1698. [cited by applicant]
Holliger et al., “Diabodies: Small Bivalent and Bispecific Antibody Fragments,” (1993) Proc. Natl. Acad. Sci. USA 90: 6444-6448. [cited by applicant]
Holliger et al., “Engineered Antibody Fragments and the Rise of Single Domains,” (2005) Nat. Biotechnol. 23(9): 1126-1136. [cited by applicant]
International Search Report and Written Opinion for International PCT Application No. PCT/US2022/030189 dated Nov. 10, 2022. [cited by applicant]
Kabat et al., “Unusual Distributions of Amino Acids in Complementarity-Determining (Hypervariable) Segments of Heavy and Light Chains of Immunoglobulins and Their Possible Roles in Specificity of Antibody-Combining Site… [cited by applicant]
Kabat, “The Structural Basis for Antibody Complementary,” Adv. Prot. Chem. (1978) 32:1-75. (Abstract Only). [cited by applicant]
Lathe, “Synthetic Oligonucleotide Probes Deduced from Amino Acid Sequence Data,” J. Molec. Biol. (1985) 183:1-12. [cited by applicant]
Lee et al., “Prolonged Circulating Lives of Single Chain Fv Proteins Conjugated with Polyethylene Glycol: A Comparison of Conjugation Chemistries and Compounds,” (1999) Bioconj. Chem. 10(6): 973-981. (Abstract Only). [cited by applicant]
Lipsky et al., “Infliximab and Methotrexate in the Treatment of Rheumatoid Arthritis,” (2000) New Engl. J. Med. 343(22):1594-1602. [cited by applicant]
Liu et al., “Chimeric Mouse-Human IgG1 Antibody that can Mediate Lysis of Cancer Cells,” Proc Natl. Acad. Sci., USA (1987) 84:3439-3443. [cited by applicant]
Liu et al., “Production of a Mouse-Human Chimeric Monoclonal Antibody to CD20 with Potent Fc-Dependent Biologic Activity,” J. Immunology (1987) 139(10):3521-3526. [cited by applicant]
Liu et al., “Randomised, Double Blind, Placebo Controlled Study of Interferon Beta-1a in Relapsing-Remitting Multiple Sclerosis Analysed by Area under Disability/Time Curves,” J. Neurol. Neurosurg. Psych. (1999) 67:451-… [cited by applicant]
Marks et al., “By-Passing Immunization,” J. Mol. Biol. (1991) 222: 581-597. [cited by applicant]
Milgrom et al., “Treatment of Allergic Asthma with Monoclonal Anti-IgE Antibody,” New Engl. J. Med. (1999) 341:1966-1973. [cited by applicant]
Morrison et al., “Chimeric Human Antibody Molecules: Mouse Antigen-Binding Domains with Human Constant Region Domains,” Proc. Natl. Acad. Sci. USA (1984) 81:6851-6855. [cited by applicant]
Muller, “[43] Determination of Affinity and Specificity of Anti-Hapten Antibodies by Competitive Radioimmunoassay,” Meth. Enzymol. (1983) 92:589-601. (Abstract Only). [cited by applicant]
Muyldermans et al., “Recognition of Antigens by Single-Domain Antibody Fragments: the Superfluous Luxury of Paired Domains,” (2001) Trends Biochem. Sci. 26(4):230-235. [cited by applicant]
Pain et al., “Preparation of Protein A-Peroxidase Monoconjugate Using a Heterobifunctional Reagent, and its Use in Enzyme Immunoassays,” (1981) J. Immunol. Meth. 40(2): 219-230. (Abstract Only). [cited by applicant]
Pluckthun, “Antibodies from [cited by applicant]
Portielji et al., “IL-12: A Promising Adjuvant for Cancer Vaccination,” Cancer Immunol. Immunother. (2003) 52:133-144. [cited by applicant]
Presta, “Selection, Design, and Engineering of Therapeutic Antibodies,” J. Allergy Clin. Immunol. (2005) 116(4):731-736. [cited by applicant]
Reichmann et al., “Reshaping Human Antibodies for Therapy,” (1988) Nature 332(6162): 323-327. [cited by applicant]
Rowley et al., “A Protein Epitope Targeted by the Antibody Response to Kawasaki Disease,” Pediatrics, Northwestern (Jan. 10, 2019) pp. 1-2. [cited by applicant]
Silva et al., “The S228P Mutation Prevents in Vivo and in Vitro IgG4 Fab-arm Exchange as Demonstrated using a Combination of Novel Quantitative Immunoassays and Physiological Matrix Preparation,” J Biol Chem, 290(9):546… [cited by applicant]
Slamon et al., “Use of Chemotherapy Plus a Monoclonal Antibody against HER2 for Metastatic Breast Cancer that Overexpresses HER2,” (2001) New Engl. J. Med. 344(11):783-792. [cited by applicant]
Tsurushita et al., “Humanization of a Chicken Anti-IL-12 Monoclonal Antibody,” J. Immuno. Methods (2004) vol. 295, pp. 9-19. [cited by applicant]
Wen et al., “Poly(ethylene glycol)-Conjugated Anti-EGF Receptor Antibody C225 with Radiometal Chelator Attached to the Termini of Polymer Chains,” (2001) Bioconj. Chem. 12(4): 545-553. (Abstract Only). [cited by applicant]
Xie, “A Highly Resolved Spatial and Functional Map of the Ruminant Gastrointestinal Microbiome,” Unpublished (Nov. 20, 2020) pp. 1-4. [cited by applicant]
Yang et al., “A Randomized Trial of Bevacizumab, an Anti-Vascular Endothelial Growth Factor Antibody, for Metastatic Renal Cancer,” (2003) New Engl. J. Med. 349(5):427-434. [cited by applicant]
Morrison, et al. Chimeric Human Antibody Molecules: Mouse Antigen-Binding Domains with Human Constant Region Domains, Pro. Natl. Aca. Sci. USA, vol. 81, pp. 6851-6855, Nov. 1984, Immunology. [cited by applicant]
Yang, et al, A Randomized Trial of Bevacizumab, an Anti-Vascular Endothelial Growth Factor Antibody, for Metastatic Renal Cancer, New England Journal of Medicine, Jul. 31, 2003; 349(5); 427-434. [cited by applicant]
Bayly-Jones, et al. The mystery behind membrane insertion: a review of the complement membrane attacl complex, Phil. Trans. R. Soc.; vol. 372, Feb. 21, 2016. [cited by applicant]
Grohar-Murray, et al. Self-care to manage fatigue among myasthenia gravis patients, Journal of Neuroscience Nusring, vol. 30 Issue 3, Jun. 1998. [cited by applicant]
Silva, et al. The S228P Mutation Prevents in Vivo and in Vitro IgG4 Fab-arm Exchange as Demonstrated using a Combination of Novel Quantitative Immunoassays and Physiological Matrix Preparation, The The Journal of Biolog… [cited by applicant]
Cella, et al., Brief measures of health-related quality of life for clinical research in neurology, Qual. Life Clin. Res. Neurol. 2012; 78:1860-1867. [cited by applicant]
Kusumoto, et al., Human genes for complement components C1r and C1s in a close tail-to-tail arrangement, Proc. Natl. Acad. Sci. USA 85(19), 7307-7311 (1988). [cited by applicant]
Krupp, et al., The Fatigue Severity Scale Application to Patients With Multiple Scelrosis and Systemic Lupus Erythematosus, Arch Neurol, vol. 46, Oct. 1989. [cited by applicant]
Fisk J.D. et al, Measuring the functional impact of fatigue: initial validation of the fatigue impact scale. Clin Infect Dis. 1994; 1: S79-S83. [cited by applicant]
Chalder T. et al., Development of a Fatigue Scale, Journal of Psychosom Resarch 1993; vol. 37, No. 2. pp 147-153. [cited by applicant]
Tsurushita, N., et al., Humanization of a chicken anti-IL-12 monoclonal antibody, Journal of Immunological Methods, 295 (2004) pp. 9-19. [cited by applicant]
Kohler, G., et al., Continuous cultures of fused cells secreting antibody of predefined specificity, Nature, vol. 256, Aug. 1975, pp. 495-497. [cited by applicant]
Penner, I., et al., The Fatigue Scale for Motor and Cognitive Functions (FSMC): validation of a new instrument to assess multiple sclerosis-related fatigue, Multiple Sclerosis, 2009; 15 (12), pp. 1509-1517. [cited by applicant]
Pain, et al., (1981) J. Immunol. Meth. 40:219. [cited by applicant]
U.S. Appl. No. 17/749,362 Non-Final Office Action dated Mar. 14, 2024. [cited by applicant]
Fernandez-Quintero, et al., Germline-Dependent Antibody Paratope States and Pairing Specific VH-VL Interface Dynamics, Frontiers in Immunology, vol. 12, 2021. [cited by applicant]
Rabia, L., et al. (2018) Understanding and overcoming trade-offs between antibody affinity, specificity, stability, and solubility, Biochem Eng. J. 15(137(; 365-374. [cited by applicant]
International Search Report and Written Opinion for International Application PCT/US23/80658 dated Apr. 3, 2024. [cited by applicant]
GenBank AAA51852 1 Complement Component C1s [ [cited by applicant]