IP Library Granted Patent US 12,202,898
Granted Patent B2
US 12,202,898 · App. 17/260,213 · Granted Jan 21, 2025

Heavy chain antibodies binding to CD19

Inventors: Shelley Force Aldred (Newark, CA); Wim van Schooten (Newark, CA); Katherine Harris (Newark, CA); Udaya Rangaswamy (Newark, CA); Nathan Trinklein (Newark, CA)
Assignee: TeneoTwo, Inc.
C07K16/2809A61K45/06A61P31/00A61P35/02A61K2039/505
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Quick Facts
Patent No.
US 12,202,898
App. No.
17/260,213
Granted
Jan 21, 2025
Kind
B2
Abstract

Anti-CD19 heavy chain antibodies (e.g., UniAbs™) are disclosed, along with methods of making such antibodies, compositions, including pharmaceutical compositions, comprising such antibodies, and their use to treat B cell disorders that are characterized by the expression of CD19.

Claims (39)

1. A heavy chain-only antibody that binds to CD19, wherein the heavy chain-only antibody comprises a heavy chain variable region comprising the CDR1 sequence set forth in SEQ ID NO: 4, the CDR2 sequence set forth in SEQ ID NO: 10, and the CDR3 sequence set forth in SEQ ID NO: 13.

2. The heavy chain-only antibody of claim 1 , wherein said CDR1, CDR2, and CDR3 sequences are present in a human framework.

3. The heavy chain-only antibody of claim 1 , further comprising a heavy chain constant region sequence in the absence of a CH1 sequence.

4. The heavy chain-only antibody of claim 1 , comprising a heavy chain variable region having at least 95% sequence identity to SEQ ID NO: 17.

5. The heavy chain-only antibody of claim 1 , comprising a heavy chain variable region comprising SEQ ID NO: 17.

6. A heavy chain-only antibody that binds to CD19, wherein the heavy chain-only antibody comprises a heavy chain variable region comprising the CDR1 sequence set forth in SEQ ID NO: 4, the CDR2 sequence set forth in SEQ ID NO: 10, and the CDR3 sequence set forth in SEQ ID NO: 13, in a human VH framework.

7. A multi-specific antibody comprising the heavy chain-only antibody of claim 1 .

8. The multi-specific antibody of claim 7 , which is bispecific.

9. The multi-specific antibody of claim 7 , having binding affinity to an effector cell.

10. The multi-specific antibody of claim 7 , having binding affinity to a T-cell antigen.

11. The multi-specific antibody of claim 10 , having binding affinity to CD3.

12. The heavy chain-only antibody of claim 1 , which is in a CAR-T format.

13. A pharmaceutical composition comprising the heavy chain-only antibody of claim 1 .

14. A method for the treatment of a B-cell disorder characterized by expression of CD19, comprising administering to a subject the antibody of claim 1 .

15. A kit for treating a B-cell disorder characterized by expression of CD19 in an individual in need, the kit comprising the antibody of claim 1 , and instructions for use.

16. The kit of claim 15 , further comprising at least one additional reagent.

17. The kit of claim 16 , wherein the at least one additional reagent comprises a chemotherapeutic drug.

18. A multi-specific antibody comprising an antigen-binding domain that binds to CD19, wherein the antigen binding domain comprises a heavy chain variable region comprising the CDR1 sequence set forth in SEQ ID NO: 4, the CDR2 sequence set forth in SEQ ID NO: 10, and the CDR3 sequence set forth in SEQ ID NO: 13.

19. The multi-specific antibody of claim 18 , comprising a heavy chain variable region comprising SEQ ID NO: 17.

20. The multi-specific antibody of claim 18 , which is bispecific.

21. The multi-specific antibody of claim 18 , having binding affinity to CD3.

22. A pharmaceutical composition comprising the multi-specific antibody of claim 18 .

23. A method for the treatment of a B-cell disorder characterized by expression of CD19, comprising administering to a subject the multi-specific antibody of claim 18 .

24. A bispecific antibody comprising: a) a heavy chain/light chain pair that has binding specificity for CD3, and b) a heavy chain comprising an antigen-binding domain that has binding specificity for CD19, wherein said antigen binding domain comprises a heavy chain variable region comprising the CDR1 sequence set forth in SEQ ID NO: 4, the CDR2 sequence set forth in SEQ ID NO: 10, and the CDR3 sequence set forth in SEQ ID NO: 13.

25. The bispecific antibody of claim 24 , comprising a heavy chain variable region comprising SEQ ID NO: 17.

26. An antibody that binds specifically to CD19, wherein the antibody comprises a heavy chain variable domain comprising the CDR1 sequence set forth in SEQ ID NO: 4, the CDR2 sequence set forth in SEQ ID NO: 10, and the CDR3 sequence set forth in SEQ ID NO: 13, in a human VH framework.

27. The antibody of claim 26 , comprising a heavy chain variable region comprising SEQ ID NO: 17.

28. The method of claim 14 , wherein the disorder is diffuse large B-cell lymphoma (DLBCL).

29. The method of claim 14 , wherein the disorder is acute lymphoblastic leukemia (ALL).

30. The method of claim 14 , wherein the disorder is non-Hodgkin's lymphoma (NHL).

31. The method of claim 23 , wherein the disorder is diffuse large B-cell lymphoma (DLBCL).

32. The method of claim 23 , wherein the disorder is acute lymphoblastic leukemia (ALL).

33. The method of claim 23 , wherein the disorder is non-Hodgkin's lymphoma (NHL).

34. A polynucleotide encoding the antibody of claim 1 .

35. A polynucleotide encoding the multi-specific antibody of claim 18 .

36. A vector comprising the polynucleotide of claim 34 .

37. A vector comprising the polynucleotide of claim 35 .

38. A cell comprising the vector of claim 36 .

39. A cell comprising the vector of claim 37 .

Assignments (3)
MERGER Recorded Apr 3, 2024
From: TENEOTWO, INC.
To: TENEOTWO, INC.
Reel/Frame 066995/0103 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 18, 2022
From: TENEOBIO, INC.
To: TENEOTWO, INC.
Reel/Frame 059951/0305 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 17, 2022
From: FORCE ALDRED, SHELLEY; VAN SCHOOTEN, WIM; HARRIS, KATHERINE; RANGASWAMY, UDAYA; TRINKLEIN, NATHAN
To: TENEOBIO, INC.
Reel/Frame 059937/0432 →
Continuity (2)
Provisional Application 62701281 · Jul 20, 2018
Related Publication 20210332133A1 · Oct 28, 2021
References Cited (108)
US 4816567A · Cabilly et al. · 1989 [cited by applicant]
US 5500362A · Robinson et al. · 1996 [cited by applicant]
US 5821337A · Carter et al. · 1998 [cited by applicant]
US 7541513B2 · Bruggemann et al. · 2009 [cited by applicant]
US 8367888B2 · Bruggemann et al. · 2013 [cited by applicant]
US 8883150B2 · Craig et al. · 2014 [cited by applicant]
US 9034324B2 · Kalled et al. · 2015 [cited by applicant]
US 9365655B2 · Craig et al. · 2016 [cited by applicant]
US 11186639B2 · Harris et al. · 2021 [cited by applicant]
US 11390681B2 · Harris et al. · 2022 [cited by applicant]
US 11421027B2 · Trinklein et al. · 2022 [cited by applicant]
US 11505606B2 · Trinklein et al. · 2022 [cited by applicant]
US 20010024811A1 · Khosla et al. · 2001 [cited by applicant]
US 20040229310A1 · Simmons · 2004 [cited by applicant]
US 20050048572A1 · Reilly et al. · 2005 [cited by applicant]
US 20060008548A1 · Tung · 2006 [cited by applicant]
US 20090098134A1 · Buelow · 2009 [cited by applicant]
US 20100122358A1 · Bruggemann et al. · 2010 [cited by applicant]
US 20130156769A1 · Kufer et al. · 2013 [cited by applicant]
US 20150376287A1 · Vu et al. · 2015 [cited by applicant]
US 20160166689A1 · Adler et al. · 2016 [cited by applicant]
US 20160355591A1 · Goldenberg et al. · 2016 [cited by applicant]
US 20180230225A1 · Fan · 2018 [cited by examiner]
US 20190352412A1 · Force et al. · 2019 [cited by applicant]
US 20200048348A1 · Trinklein et al. · 2020 [cited by applicant]
US 20200085839A1 · Sidransky et al. · 2020 [cited by applicant]
US 20200157232A1 · Trinklein et al. · 2020 [cited by applicant]
US 20200339685A1 · Schellenberger et al. · 2020 [cited by applicant]
US 20210047402A1 · Trinklein et al. · 2021 [cited by applicant]
US 20230082151A1 · Trinklein et al. · 2023 [cited by applicant]
US 20230272075A1 · Trinklein et al. · 2023 [cited by applicant]
WO 1996027011 · 1993 [cited by applicant]
WO 1996032478 · 1996 [cited by applicant]
WO 1997034631 · 1997 [cited by applicant]
WO 2001024811 · 2001 [cited by applicant]
WO 2001024812 · 2001 [cited by applicant]
WO 2002066516 · 2002 [cited by applicant]
WO 2006008548 · 2006 [cited by applicant]
WO 2016048938 · 2016 [cited by applicant]
WO 2017223111 · 2017 [cited by applicant]
WO 2018052503 · 2018 [cited by applicant]
WO 2018237037 · 2018 [cited by applicant]
WO 2019006072 · 2019 [cited by applicant]
WO 2020018922 · 2020 [cited by applicant]
Wang et al., “A systematic approach for analysis and characterization of mispairing in bispecific antibodies with asymmetric architecture,” (2018) mAbs 10:8, 1226-1235. [cited by applicant]
Ridgway et al., “Knobs-into-holes' engineering of antibody CH3 domains for heavy chain heterodimerization,” (1996) Protein Eng. 9(7):617-621. [cited by applicant]
Gupta et al., “Constitutive Inflammatory Cytokine Storm: A Major Threat to Human Health,” (2019) Journal of Interferon & Cytokine Research 40(1):19-23. [cited by applicant]
Crescioli et al., “lgG4 Characteristics and Functions in Cancer Immunity,” (2016) Curr Allergy Asthma Rep 16:7. [cited by applicant]
Labrijn et al., “Therapeutic IgG4 antibodies engage in Fab-arm exchange with endogenous human IgG4 in vivo,” (2009) Nature Biotechnology 27:767-71. [cited by applicant]
Muyldermans, “Single domain camel antibodies: current status,” 2001; Journal of Biotechnology 74(4):277-302. [cited by applicant]
Revets et al., “Nanobodies as Novel Agents for Cancer Therapy,” (2005) Expert Opinion Biological Therapy 5(1):111-124. [cited by applicant]
Nuttall et al., “Isolation and Characterization of an IgNAR Variable Domain Specific for the Human Mitochondrial Translocase Receptor Tom70,” (2003) Eur. J. Biochem. 270:3543-3554. [cited by applicant]
Nuttall et al., “Selection and Affinity Maturation of IgNAR Variable Domains Targeting Plasmodium falciparum AMA1,” (2004) Proteins; Structure, Function and Bioinformatics 55:187-197. [cited by applicant]
Dooley et al., “Selection and Characterization of Naturally Occuring Single-domain (IgNAR) Antibody Fragments from Immunized Sharks by Phage Display,” (2003) Molecular Immunology 40:25-33. [cited by applicant]
Jaton et al., “Recovery of Antibody Activity Upon Reoxidation of Completely Reduced Polyalanyl Heavy Chain and its Fd Fragment Derived from Anti-2,4-dinitrophenyl Antibody,” (1968) Biochemistry 7(12):4185-4195. [cited by applicant]
Sitia et al., “Developmental Regulation of IgM Secretion: The Role of the Carbosy-terminal Cysteine,” (1990) Cell, 60:781-790. [cited by applicant]
Van der Linden et al., “Comparison of Physical Chemical Properties of Llama VHH Antibody Fragments and Mouse Monoclonal Antibodies,” (1999) Biochimica et Biophysica Acta 1431:37-46. [cited by applicant]
Frenken et al., “Isolation of Antigen Specific Llama V [cited by applicant]
Ghahroudi et al., “Selection and Identification of Single Domain Antibody Fragments from Camel Heavy-chain Antibodies,” (1997) FEBS Letters 414:521-526. [cited by applicant]
Nguyen et al., “Heavy-chain only antibodies derived from dromedary are secreted and displayed by mouse B cells,” (2003) Immunology; 109(1):93-101. [cited by applicant]
Bruggemann et al., “Heavy-Chain-Only Antibody Expression and B-Cell Development in the Mouse,” (2006) Crit. Rev. Immunol. 26(5):377-90. [cited by applicant]
Zou et al., “Heavy Chain-Only Antibodies are Spontaneously Produced in Light Chain-Deficient,” (2007) J Exp Med 204(13):3271-3283. [cited by applicant]
Geurts et al., “Knockout Rats via Embryo Microinjection of Zinc-finger Nucleases,” (2009) Science 325(5939):433. [cited by applicant]
Iri-Sofla et al., “Nanobody-based Chimeric Receptor Gene Integration in Jurkat Cells Mediated by PhiC31 Integrase,” (2011) Experimental Cell Research 317:2630-2641. [cited by applicant]
Jamnani et al., “T Cells Expressing VHH-directed Oligoclonal Chimeric HER2 Antigen Receptors: Towards Tumor-directed Oligoclonal T Cell Therapy,” (2014) Biochimica et Biophysica Acta 1840:378-386. [cited by applicant]
Gras et al., “BCMAp: An Integral Membrane Protein in the Golgi Apparatus of Human Mature B Lymphocytes,” (1995) International Immunology 7(7):1093-1106. [cited by applicant]
Tai et al., “Novel Anti-B-Cell Maturation Antigen Antibody-drug Conjugate (GSK2857916) Selectively Induces Killing of Multiple Myeloma,” (2014) Blood 123(20): 3128-38. [cited by applicant]
Ali et al., “T Cells Expressing an Anti-B-Cell Maturation Antigen Chimeric Antigen Receptor Cause Remissions of Multiple Myeloma,” (2016) Blood 128(13):1688-700. [cited by applicant]
Kohler et al., “Continuous cultures of fused cells secreting antibody of predefined specificity,” (1975) Nature 256:495-497. [cited by applicant]
Chothia et al., “Canonical structures for the hypervariable regions of immunoglobulins,” (1987) Journal of Molecular Biology 196(4):901-917. [cited by applicant]
Lefranc et al., “IMGT, the international ImMunoGeneTics database,” (1999) Nucleic Acids Research, 27(1):209-212. [cited by applicant]
Zhao et al., “A germline knowledge based computational approach for determining antibody complementarity determining regions,” (2010) Molecular Immunology 47(4):694-700. [cited by applicant]
Chothia et al., “Conformations of immunoglobulin hypervariable regions,” (1989) Nature 342:877-883. [cited by applicant]
Honegger, “Yet Another numbering scheme for immunoglobulin variable domains: an automatic modeling and analysis tool,” (2001) Journal of Molecular Biology 309(3):657-670. [cited by applicant]
Ofran et al. “Automated identification of complementarity determining regions (CDRs) reveals peculiar characteristics of CDRs and B-cell epitopes,” (2008) Journal of Immunology 181(9):6230-6235. [cited by applicant]
Almagro “Identification of differences in the specificity-determining residues of antibodies that recognize antigens of different size: implications for the rational design of antibody repertoires,” (2004) Journal of Mo… [cited by applicant]
Padlan et al., “Identification of specificity-determining residues in antibodies,” (1995) FASEB Journal 9(1):133-139. [cited by applicant]
Roux et al., “Comparisons of the Ability of Human IgG3 Hinge Mutants, IgM, IgE, and IgA2, to Form Small Immune Complexes: A Role for Flexibility and Geometry,” (1998) Journal of Immunology 161(8):4083-4090. [cited by applicant]
Lund et al., “Expression and characterization of truncated forms of humanized L243 IgG1,” (2000) European Journal of Biochemistry 267(24):7246-7256. [cited by applicant]
Boesch et al., “Highly parallel characterization of IgG Fc binding interactions,” (2014) MAbs 6(4):915-927. [cited by applicant]
Chen et al., “Fusion protein linkers: Property, design and functionality ,” (2013) Advanced Drug Delivery Reviews 65(10): 1357-1369. [cited by applicant]
Hamers-Casterman et al., “Naturally Occurring Antibodies Devoid of Light Chains,” (1993) Letters to Nature 363:446-448. [cited by applicant]
Desmyter et al., “Antigen Specificity and High Affinity Binding Provided by One Single Loop of a Camel Single-domain Antibody,” (2001) Journal of Biological Chemistry 276(28):26285-26290. [cited by applicant]
Jackson et al., “Driving CAR T-cells Forward,” (2016) Nature Reviews Clinical Oncology 13:370-383. [cited by applicant]
Ravetch et al., “Fc Receptors,” (1991) Annual Review of Immunology 9:457-492. [cited by applicant]
Clynes et al., “Fc Receptors are Required in Passie and Active Immunity to Melanoma,” (1998) PNAS (USA) 95(2):652-656. [cited by applicant]
Gazzano-Santoro et al., “A non-radioactive complement-dependent cytotoxicity assay for anti-CD20 monoclonal antibody,” (1996) Journal of Immunological Methods 202(2):163-171. [cited by applicant]
Concepcion et al., “Label-Free Detection of Biomolecular Interactions Using BioLayer Interferometry for Kinetic Characterization,” (2009) Combinatorial Chemistry & High Throughput Screening 12(8):791-800. [cited by applicant]
Menoret et al., “Characterization of Immunoglobulin Heavy Chain Knockout Rats,” (2010) European Journal Immunology 40:2932-2941. [cited by applicant]
Cui et al., “Targeted Integration in Rat and Mouse Embryos with Zinc-finger Nucleases,” (2011) Nature Biotechnology 29(1):64-67. [cited by applicant]
Carpenter et al., “B-cell Maturation Antigen Is a Promising Target for Adoptive T-cell Therapy of Multiple Myeloma,” (2013) Clinical Cancer Research 19(8):2048-2060. [cited by applicant]
Tai et al., “APRIL and BCMA promote human multiple myeloma growth and immunosuppression in the bone marrow microenvironment,” (2016) Blood 127(25):3225-3236. [cited by applicant]
Sanz et al., “B Cells as Therapeutic Targets in SLE,” (2010) Nature Reviews Rheumatology 6:326-337. [cited by applicant]
Dai et al., “Chimeric Antigen Receptors Modified T-cells for Cancer Therapy,” (2016) J Natl Cancer Inst 108(7):dvj439. [cited by applicant]
Omniab, “Naturally Optimized Human Antibodies,” (Feb. 23, 2016) retrieved from Internet: URL:http://content.stockpr.com/omniab/db/252/746/file/OmniAb.pdf. [cited by applicant]
Armitage, “A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma,” (1997) Blood 89(11):3909-3918. [cited by applicant]
Hanes et al., “New advances in microsphere-based single-dose vaccines,” (1997) Advanced Drug Delivery Reviews 28(1):97-119. [cited by applicant]
Langer, “New Methods of Drug Delivery,” (1990) Science 249(4976):1527-1533. [cited by applicant]
Banihashemi et al., “Development of Specific Nanobodies (VHH) for CD19 Immuno-targeting of Human B-lymphocytes,” (2018) Iranian Journal of Basic Medical Sciences 21(5):455-464. [cited by applicant]
Malik et al., “A Novel Fully Human Bispecific CD19 x CD3 Antibody that Kills Lymphoma Cells with Minimal Cytokine Secretion,” (2018) 132(1):1671. [cited by applicant]
Naddafi et al., “Anti-CD19 Monoclonal Antibodies: A New Approach to Lymphoma Therapy,” (2015) IJMCM 4(3):143-151. [cited by applicant]
Sadelain et al., “CD19 Car T Cells,” (2017) Cell 171:1471. [cited by applicant]
Miller et al., “Design, Construction, and In Vitro Analyses of Multivalent Antibodies,” (2003) Jour. of Immunology 170(9):4854-4861. [cited by applicant]
Duncan et al., “Localization of the binding site for the human high-affinity Fc receptor on IgG ,” (1988) Nature 332:563-564. [cited by applicant]
Tao et al., “Structural features of human immunoglobulin G that determine isotype-specific differences in complement activation,” (1993) Journal of Experimental Medicine 178(2):661-667. [cited by applicant]
Canfield et al.“ The Binding Affinity of Human IgG for its High Affinity Fc Receptor Is Determined by Multiple Amino Acids in the CH2 Domain and Is Modulated by the Hinge Region,” J. Exp. Med. 173:1483-1491, (1991) J. E… [cited by applicant]
Armour et al., “Recombinant human IgG molecules lacking Fcγ receptor I binding and monocyte triggering activities,” (1999) Eur J Immunol. 29(8):2613-2624. [cited by applicant]
Shields et al., “High Resolution Mapping of the Binding Site on Human IgG1 for FcγRI, FcγRII, FcγRIII, and FcRn and Design of IgG1 Variants with Improved Binding to the FcγR,” (2001) J Biol Chem. 276(9):6591-6604. [cited by applicant]