IP Library › Granted Patent US 12,428,474
Granted Patent B2
US 12,428,474 · App. 17/649,889 · Granted Sep 30, 2025

Antibodies comprising a common light chain and uses thereof

Inventors: Thomas Charpentier (Philadelphia, PA); Ross Stewart Chambers (Philadelphia, PA); Lewis J. Stafford (Philadelphia, PA); Trevor Barnes (Philadelphia, PA); Jonathan T. Sullivan (Philadelphia, PA)
Assignee: Integral Molecular, Inc.
C07K16/18A61K38/00C07K2317/24C07K2317/565C07K2317/622
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 12,428,474
App. No.
17/649,889
Granted
Sep 30, 2025
Kind
B2
Abstract

Peptides and uses thereof, such as a common light chain in an antibody, are provided.

Claims (21)

1. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and an antibody light chain variable region comprising a light chain CDR1 (LCDR1), CDR2 (LCDR2), and CDR3 (LCDR3), wherein the light chain variable region comprises:

an LCDR 1 amino acid sequence of SEQ ID NO: 19; an LCDR2 amino acid sequence of SEQ ID NO: 21; and an LCDR3 amino acid sequence of SEQ ID NO: 23;

an LCDR 1 amino acid sequence of SEQ ID NO: 52; an LCDR2 amino acid sequence of SEQ ID NO: 54; and an LCDR3 amino acid sequence of SEQ ID NO: 56;

an LCDR 1 amino acid sequence of SEQ ID NO: 58; an LCDR2 amino acid sequence of SEQ ID NO: 60; and an LCDR3 amino acid sequence of SEQ ID NO: 61;

an LCDR 1 amino acid sequence of SEQ ID NO: 63; an LCDR2 amino acid sequence of SEQ ID NO: 64; and an LCDR3 amino acid sequence of SEQ ID NO: 65;

an LCDR 1 amino acid sequence of SEQ ID NO: 66; an LCDR2 amino acid sequence of SEQ ID NO: 67; and an LCDR3 amino acid sequence of SEQ ID NO: 68; or

an LCDR 1 amino acid sequence of SEQ ID NO: 84; an LCDR2 amino acid sequence of SEQ ID NO: 64; and an LCDR3 amino acid sequence of SEQ ID NO: 73.

2. The pharmaceutical composition of claim 1 , wherein the light chain variable region comprises an LCDR1 amino acid sequence of SEQ ID NO: 19; an LCDR2 comprising amino acid sequence of SEQ ID NO: 21; and an LCDR3 amino acid sequence of SEQ ID NO: 23.

3. The pharmaceutical composition of claim 1 , wherein the light chain variable region comprises an LCDR1 amino acid sequence of SEQ ID NO: 52; an LCDR2 amino acid sequence of SEQ ID NO: 54; and an LCDR3 amino acid sequence of SEQ ID NO: 56.

4. The pharmaceutical composition of claim 1 , wherein the light chain variable region comprises an LCDR1 amino acid sequence of SEQ ID NO: 58; an LCDR2 amino acid sequence of SEQ ID NO: 60; and an LCDR3 amino acid sequence of SEQ ID NO: 61.

5. The pharmaceutical composition of claim 1 , wherein the light chain variable region comprises an LCDR1 amino acid sequence of SEQ ID NO: 63; an LCDR2 amino acid sequence of SEQ ID NO: 64; and an LCDR3 amino acid sequence of SEQ ID NO: 65.

6. The pharmaceutical composition of claim 1 , wherein the light chain variable region comprises an LCDR1 amino acid sequence of SEQ ID NO: 66; an LCDR2 amino acid sequence of SEQ ID NO: 67; and an LCDR3 amino acid sequence of SEQ ID NO: 68.

7. The pharmaceutical composition of claim 1 , wherein the light chain variable region comprises an LCDR1 amino acid sequence of SEQ ID NO: 84; an LCDR2 amino acid sequence of SEQ ID NO: 64; and an LCDR3 amino acid sequence of SEQ ID NO: 73.

8. A nucleic acid encoding an antibody light chain variable region comprising a light chain CDR1 (LCDR1), CDR2 (LCDR2), and CDR3 (LCDR3), wherein the light chain variable region comprises:

an LCDR1 amino acid sequence of SEQ ID NO: 19; an LCDR2 amino acid sequence of SEQ ID NO: 21; and an LCDR3 amino acid sequence of SEQ ID NO: 23;

an LCDR1 amino acid sequence of SEQ ID NO: 52; an LCDR2 amino acid sequence of SEQ ID NO: 54; and an LCDR3 amino acid sequence of SEQ ID NO: 56;

an LCDR1 amino acid sequence of SEQ ID NO: 58; an LCDR2 amino acid sequence of SEQ ID NO: 60; and an LCDR3 amino acid sequence of SEQ ID NO: 61;

an LCDR1 amino acid sequence of SEQ ID NO: 63; an LCDR2 amino acid sequence of SEQ ID NO: 64; and an LCDR3 amino acid sequence of SEQ ID NO: 65;

an LCDR1 amino acid sequence of SEQ ID NO: 66; an LCDR2 amino acid sequence of SEQ ID NO: 67; and an LCDR3 amino acid sequence of SEQ ID NO: 68; or

an LCDR1 amino acid sequence of SEQ ID NO: 84; an LCDR2 amino acid sequence of SEQ ID NO: 64; and an LCDR3 amino acid sequence of SEQ ID NO: 73.

9. A cell comprising the nucleic acid molecule of claim 8 .

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 3, 2022
From: CHARPENTIER, THOMAS; CHAMBERS, ROSS STEWART; STAFFORD, LEWIS J.; BARNES, TREVOR; SULLIVAN, JONATHAN T.
To: INTEGRAL MOLECULAR, INC.
Reel/Frame 058882/0505 →
Continuity (3)
Continuation 16789626 · Feb 13, 2020
Provisional Application 62806052 · Feb 15, 2019
Related Publication 20220372121A1 · Nov 24, 2022
References Cited (118)
US 4376110A · David et al. · 1983 [cited by applicant]
US 4699880A · Goldstein · 1987 [cited by applicant]
US 4816567A · Cabilly et al. · 1989 [cited by applicant]
US 4946778A · Ladner et al. · 1990 [cited by applicant]
US 5260203A · Ladner et al. · 1993 [cited by applicant]
US 5475096A · Gold et al. · 1995 [cited by applicant]
US 5831012A · Nilsson et al. · 1998 [cited by applicant]
US 6004746A · Brent et al. · 1999 [cited by applicant]
US 6005079A · Casterman et al. · 1999 [cited by applicant]
US 6794144B1 · Saksela et al. · 2004 [cited by applicant]
US 6818418B1 · Lipovsek et al. · 2004 [cited by applicant]
US 6994982B1 · Watt et al. · 2006 [cited by applicant]
US 7105653B2 · Shanafelt et al. · 2006 [cited by applicant]
US 7166697B1 · Galanis et al. · 2007 [cited by applicant]
US 7186524B2 · Kolmar et al. · 2007 [cited by applicant]
US 7250297B1 · Beste et al. · 2007 [cited by applicant]
US 7417130B2 · Stumpp et al. · 2008 [cited by applicant]
US 7763258B2 · Doms et al. · 2010 [cited by applicant]
US 7803907B2 · Stemmer et al. · 2010 [cited by applicant]
US 7838629B2 · Fiedler et al. · 2010 [cited by applicant]
US 8158130B2 · Doms et al. · 2012 [cited by applicant]
US 8377691B2 · Doranz · 2013 [cited by applicant]
US 9074002B2 · Tonks et al. · 2015 [cited by applicant]
US 9428567B2 · Garcia et al. · 2016 [cited by applicant]
US 9580486B2 · Gavin et al. · 2017 [cited by applicant]
US 9616106B2 · Basile · 2017 [cited by applicant]
US 10336818B2 · Chamberlain et al. · 2019 [cited by applicant]
US 11254736B2 · Charpentier · 2022 [cited by examiner]
US 20040023334A1 · Prior · 2004 [cited by applicant]
US 20040132094A1 · Etzerodt et al. · 2004 [cited by applicant]
US 20040141980A1 · Ignjatovic et al. · 2004 [cited by applicant]
US 20040146938A1 · Nguyen et al. · 2004 [cited by applicant]
US 20040157209A1 · Mlmaz et al. · 2004 [cited by applicant]
US 20040209243A1 · Nixon et al. · 2004 [cited by applicant]
US 20050123563A1 · Doranz et al. · 2005 [cited by applicant]
US 20060269515A1 · Denis-Mize et al. · 2006 [cited by applicant]
US 20100119446A1 · Grabulovski et al. · 2010 [cited by applicant]
US 20100239633A1 · Strome et al. · 2010 [cited by applicant]
US 20120195882A1 · Doms et al. · 2012 [cited by applicant]
US 20120301476A1 · Okano et al. · 2012 [cited by applicant]
US 20140120092A1 · Gros · 2014 [cited by examiner]
US 20140127219A1 · Sahin et al. · 2014 [cited by applicant]
US 20140286898A1 · Gavin et al. · 2014 [cited by applicant]
US 20170003712A1 · Funk et al. · 2017 [cited by applicant]
US 20170051029A1 · Greve · 2017 [cited by applicant]
US 20170355756A1 · Julien et al. · 2017 [cited by applicant]
US 20180044434A1 · Sato et al. · 2018 [cited by applicant]
US 20200262898A1 · Charpentier et al. · 2020 [cited by applicant]
US 20200262915A1 · Chambers et al. · 2020 [cited by applicant]
CN 102746397A · 2012 [cited by applicant]
CN 103483449A · 2014 [cited by applicant]
EA 0171496 · 1986 [cited by applicant]
EP 0125023A1 · 1984 [cited by applicant]
EP 0173494A2 · 1986 [cited by applicant]
EP 0184187A2 · 1986 [cited by applicant]
EP 0404097A2 · 1990 [cited by applicant]
TW 201125580A · 2011 [cited by applicant]
WO 1986001533 · 1986 [cited by applicant]
WO 1987002671A1 · 1987 [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 2008068048A2 · 2008 [cited by applicant]
WO 2009025759A1 · 2009 [cited by applicant]
WO 2010085495A1 · 2010 [cited by applicant]
WO WO2010126590A1 · 2010 [cited by examiner]
WO 2014016737 · 2014 [cited by applicant]
WO 2014153111A3 · 2014 [cited by applicant]
WO 2016025385A1 · 2016 [cited by applicant]
WO 2016014428A3 · 2016 [cited by applicant]
WO WO2016164468A2 · 2016 [cited by examiner]
WO 2016164937A3 · 2017 [cited by applicant]
WO 2017192567A1 · 2017 [cited by applicant]
WO 2018067198 · 2018 [cited by applicant]
WO 2019031965A1 · 2019 [cited by applicant]
Almagro, “Identification of differences in the specificity-determining residues of antibodies that recognize antigens of differenct size: implications for the rational design of antibody repertoires”, J. Mol. Reconit. (… [cited by applicant]
Baert, et al., “Influence of Immunogenicity on the Long-Term Efficacy of Infliximab in Crohn's Disease”, New Engl. J. Med. (2003) 348:601-608. [cited by applicant]
Better et al., “ [cited by applicant]
Bird, et al., “Single-Chain Antigen-Binding Proteins”, Science, (1998) vol. 242, pp. 432-426. [cited by applicant]
Boulianne, et al., “Production of functional chimaeric mouse/human antibody”, Nature (1984) 312:643 646. [cited by applicant]
Cabilly, et al., “Generation of antibody activity from immunoglobulin polypeptide chaings produced in [cited by applicant]
Chen, et al., “Enhancement and destruction of antibody function by somatic mutation: unequal occurrence if controlled by V gene combinatorial associates”, The EMBO Journal (1995) vol. 14, No. 12, pp. 2784-2794. [cited by applicant]
Chothia, et al., “Canonical Structures for the Hypervariable Regions of Immunoglobulins”, Mol. Biol. (1987) 196:901-917. [cited by applicant]
Extended Search Report issued in 20756721.5 dated Nov. 17, 2022. [cited by applicant]
Hodgson et al., “Making Monoclonals In Microbes”, BioTechnology (1991) 9:421-425. [cited by applicant]
Holliger at al., “Engineered Antibody Fragments and the Rise of Single Domains”, Nat. Biotechnol. (2005) 23:1126-1136. [cited by applicant]
Holliger et al. “Diabodies”: Small bivalent and bispecific antibody fragments, Proc Natl. Acad. Sci. USA (1993) 90:6444-5448. [cited by applicant]
Juston et al., “Protein engineering of antibody binding sites Recovery of specific activity in an anti-digoxin single-chain Fv analogue produced in [cited by applicant]
Koenig, et al., “Mutational landscape of antibody variable domains reveals a switch modulating the interdomain conformational dynamics and antigen binding”, PNAS (2017) pp. E486-E495, www.pnas.org/cgi/doi/10.1073/pnas.1… [cited by applicant]
Kohler, et al., “Continuous cultures of fused cells secreting antibody of predefined specificity”, Nature (1975) vol. 256: pp. 495 497. [cited by applicant]
Kozbor, et al., “The production of monoclonal antibodies from human lymphocytes”, Immunol. Today (1983) 4:72 79. [cited by applicant]
Kussie, et al., “A Single Engineered Amino Acid Substituion Changes Antibody Fine Specificity1”, J immunol (1994) 152(1): pp. 146-152. [cited by applicant]
Lathe et al., “Synthetic oligonucleotide probes deduced from amino acid sequence data. Theroetical and practical considerations”, J. Molec. Biol. (1985) 183:1-12. [cited by applicant]
Lefranc et al., “IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains” Developmental & Comparative Immunology (2003) 27:55-77. [cited by applicant]
Liu et al., “Production of a mouse-human chimeric monoclonal antibody to CD20 with potent Fc-dependent biologic activity”, J. Immunolo. (1987) 139(10):3521-6. [cited by applicant]
Liu, et al., “Chimeric mouse-human IgG1 antibody that can mediate lysis of cancer cells”, Proc. Nationl. Acad. Sci. (1987) 84:3439-3433. [cited by applicant]
Milgrom et al., “Treatment of Allergic Asthma with Monoclonal Anti-IgE Antibody”, (1999) New Engl. J. Med. 341:1966-1973. [cited by applicant]
Morrison, et al., “Chimeric human antibody molecules: Mouse antigen-binding domains with humane constant region domains”, (1984) Proc. Natl. Acad. Sci. USA 81:6851-6855. [cited by applicant]
Muller et al., “Determination of Affinity and Specificity of Anti-Hapten Antibodies by Competitive Radioimmunoassay”, Meth. Enzymol. (1983) 92:589-601. [cited by applicant]
Neuberger, et al., “A hapten-specific chimaeric IgE antibody with human physiological effector function”, Nature (1985) vol. 314 pp. 268-270. [cited by applicant]
Nishibori, et al., “Humanization of chicken monoclonal antibody using phage-display system”, Molecular Immunology (2006) 43 pp. 634-642. [cited by applicant]
Non-final Office Action received in U.S. Appl. No. 16/789,626, mailed Mar. 30, 2021. [cited by applicant]
Queen, et al., “A humanized antibody that binds to the interleukin 2 receptor”, Proc. Natil. Acad. Sci (1989), 86:10029-10032. [cited by applicant]
Reichmann et al., “Single domain antibodies: comparison of camel VH and camelised human VH domains”, J. Immunol Method (1999) 231:25. [cited by applicant]
Riechmann, et al., “Reshaping human antibodies for therapy”, Nature (1988) 332 (6162): vol. pp. 323-327. [cited by applicant]
Sahagan, et al., “A genetically engineered murine/human chimeric antibody retains specificity for human tumor-associated antigen.”, J. Immunol. (1986) 137:pp. 1066-1074. [cited by applicant]
Slamon et al. “Use of Chemotherapy Plus a Monoclonal Antibody Against HER2 for Metastatic Breast Cancer that Overexpresses HER2”, New Engl. J. Med. (2001) 344:783-792. [cited by applicant]
Storz et al., “Intellectual property protection Strategies for future antibody inventions”, MAbs. (2011) 3(3): 310-317. [cited by applicant]
Sun, et al., “Chimeric antibody with human constant regions and mouse variable regions directed against carcinoma-associated antigen 7-1A”, Proc. Natil. Acad. Sci. (1987) 84:214-218. [cited by applicant]
Tsurushita, et al., “Humanization of a chicken anti-IL-12 monoclonal antibody”, Journal of Immunological methods, 2004) 295, pp. 9-19. [cited by applicant]
UniProtKB Accession No. A0A2V9M896_9BACT, Sialidase domain-containint protein, (2018). [cited by applicant]
Wahl et al., “Improved Radioimingin and Tumor Localizaton with Monoclonal F(ab′)2”, J. Nucl. Med. (1983) 24:316 325. [cited by applicant]
Ward, et al., “Binding activities of a repertoire of single immunoglobulin variable domains secreted from [cited by applicant]
Wu et al., “An analysis of the sequences of the variable regions of bence jones proteins and myeloma light chains and their implications for anti-body complementarity”, Journal of Experimental Medicine (1970) 132: pp. 2… [cited by applicant]
U.S. Appl. No. 16/789,626, filed Feb. 13, 2020, Thomas Charpentier, et al. [cited by applicant]
Krah S, et al., Generation of human bispecific common light chain antibodies by combining animal immunization and yeast display, Protein Eng Des Sel, 30(4):291-301 (2017). [cited by applicant]
Krah S, et al., Engineering bispecific antibodies with defined chain pairing, New Biotechnology, 39:167-173 (2017). [cited by applicant]