IP Library › Granted Patent US 12,570,765
Granted Patent B2
US 12,570,765 · App. 18/758,038 · Granted Mar 10, 2026

Trispecific T cell engagers

Inventors: Margaret Karow (Newbury Park, CA); Richard Yau (Newbury Park, CA); Jackie Sheng (Newbury Park, CA)
Assignee: SUZHOU ZELGEN BIOPHARMACEUTICALS CO. LTD.
C07K16/3092A61K39/39558A61K45/06C07K16/28C07K16/2809C07K16/2818C07K16/2878C07K16/30C07K16/468A61K2039/505C07K2317/24C07K2317/31C07K2317/52C07K2317/55C07K2317/565C07K2317/622C07K2317/732C07K2317/74C07K2317/75C07K2319/33
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Quick Facts
Patent No.
US 12,570,765
App. No.
18/758,038
Granted
Mar 10, 2026
Kind
B2
Abstract

Provided are trispecific T Cell Engagers or TSMAb's, antibodies that can simultaneously engage three different types of epitopes on the same target or on different targets. More specifically, the invention is directed to trispecific molecules that bind to DLL3, MUC17 or CLDN18.2 and activate CD (cluster of differentiation) molecules (e.g. CD3, CD28 and CD137). Also provided are methods of treating an ailment such as cancer using an antibody (or fragment) against DLL3, MUC17 or CLD18 paired with an antibody (or fragment) of an agonist antibody that activates CD3, CD28 and/or CD137.

Claims (12)

1 . An anti-CD28, anti-CD3, and anti-DLL3 trispecific antibody, comprising:

a first peptide chain comprising (1) an anti-CD28 single chain fragment variable region (scFv), (2) an anti-CD3 scFv and (3) one peptide chain of a fragment crystallizable region (Fc region);

a second peptide chain comprising (1) one peptide chain of an anti-DLL3 Fab fragment and (2) another peptide chain of the Fc region; and

a third peptide chain comprising another peptide chain of the anti-DLL3 Fab fragment, and

wherein the first peptide chain comprises SEQ ID NO: 481, the second peptide chain comprises SEQ ID NO: 276 and the third peptide chain comprises SEQ ID NO: 302; or

wherein the first peptide chain comprises SEQ ID NO: 481, the second peptide chain comprises SEQ ID NO: 291 and the third peptide chain comprises SEQ ID NO: 295; or

wherein the first peptide chain comprises SEQ ID NO: 481, the second peptide chain comprises SEQ ID NO: 290 and the third peptide chain comprises SEQ ID NO: 298; or

wherein the first peptide chain comprises SEQ ID NO: 481, the second peptide chain comprises SEQ ID NO: 276 and the third peptide chain comprises SEQ ID NO: 297.

2 . The trispecific antibody of claim 1 , wherein the first peptide chain comprises SEQ ID NO: 481, the second peptide chain comprises SEQ ID NO: 276 and the third peptide chain comprises SEQ ID NO: 302.

3 . The trispecific antibody of claim 1 , wherein the first peptide chain comprises SEQ ID NO: 481, the second peptide chain comprises SEQ ID NO: 291 and the third peptide chain comprises SEQ ID NO: 295.

4 . The trispecific antibody of claim 1 , wherein the first peptide chain comprises SEQ ID NO: 481, the second peptide chain comprises SEQ ID NO: 290 and the third peptide chain comprises SEQ ID NO: 298.

5 . The trispecific antibody of claim 1 , wherein the first peptide chain comprises SEQ ID NO: 481, the second peptide chain comprises SEQ ID NO: 276 and the third peptide chain comprises SEQ ID NO: 297.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 16, 2025
From: GENSUN BIOPHARMA INC.
To: ZELGEN HOLDINGS LIMITED
Reel/Frame 073225/0789 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 16, 2025
From: ZELGEN HOLDINGS LIMITED
To: SUZHOU ZELGEN BIOPHARMACEUTICALS CO. LTD.
Reel/Frame 073226/0963 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 17, 2024
From: KAROW, MARGARET; YAU, RICHARD; SHENG, JACKIE
To: GENSUN BIOPHARMA INC.
Reel/Frame 068011/0234 →
Continuity (5)
Continuation 17164696 · Feb 1, 2021
Provisional Application 62991070 · Mar 17, 2020
Provisional Application 62981048 · Feb 25, 2020
Provisional Application 62968999 · Jan 31, 2020
Related Publication 20240425611A1 · Dec 26, 2024
References Cited (51)
US 4676980A · Segal et al. · 1987 [cited by applicant]
US 4816567A · Cabilly et al. · 1989 [cited by applicant]
US 4946778A · Ladner et al. · 1990 [cited by applicant]
US 5545806A · Lonberg et al. · 1996 [cited by applicant]
US 5545807A · Surani et al. · 1996 [cited by applicant]
US 5569825A · Lonberg et al. · 1996 [cited by applicant]
US 5625126A · Lonberg et al. · 1997 [cited by applicant]
US 5633425A · Lonberg et al. · 1997 [cited by applicant]
US 5661016A · Lonberg et al. · 1997 [cited by applicant]
US 20160032006A1 · Hudson · 2016 [cited by applicant]
US 20160355600A1 · Moore · 2016 [cited by examiner]
US 20180044415A1 · Escarpe et al. · 2018 [cited by applicant]
US 20190263907A1 · Raum et al. · 2019 [cited by applicant]
WO 9100360 · 1991 [cited by applicant]
WO 9308829 · 1995 [cited by applicant]
WO 2018191438 · 2018 [cited by applicant]
WO 2019126748 · 2019 [cited by applicant]
WO 2019133961 · 2019 [cited by applicant]
WO 2019140196 · 2019 [cited by applicant]
Ni et al., The Protein Journal, 43, pp. 683-696, Jul. 2024 (Year: 2024). [cited by examiner]
Owen et al., Journal of Hematology & Oncology, Publication Date: Jun. 18, 2019 (Year: 2019). [cited by examiner]
Willems et al., Cancer Immunol Immunother, 54: 1059-1071, Publication Date: May 13, 2005 (Year: 2005). [cited by examiner]
McCafferty J, Griffiths AD, Winter G, Chiswell DJ. Phage antibodies: filamentous phage displaying antibody variable domains. Nature. Dec. 6, 1990;348(6301):552-4. [cited by applicant]
Sundaresan et al., J Nucl Med 44:1962-9 (2003). [cited by applicant]
Temple F Smith, Michael S Waterman, Comparison of biosequences,Advances in Applied Mathematics, vol. 2, Issue 4, 1981, pp. 482-489. [cited by applicant]
Saul B. Needleman, Christian D. Wunsch, A general method applicable to the search for similarities in the amino acid sequence of two proteins, Journal of Molecular Biology, vol. 48, Issue 3, 1970, pp. 443-453. [cited by applicant]
Pearson WR, Lipman DJ. Improved tools for biological sequence comparison. Proc Natl Acad Sci U S A. Apr. 1988;85(8):2444-8. [cited by applicant]
Altschul SF, Madden TL, Schäffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. Sep. 1, 1997;25(17):3389-402. [cited by applicant]
Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J Mol Biol. Oct. 5, 1990;215(3):403-10. [cited by applicant]
Mark A. Batzer, James E. Carlton, Prescott L. Deininger, Enhanced evolutionary PCR using oligonucleotides with inosine at the 3′-terminus, Nucleic Acids Research, vol. 19, Issue 18, Sep. 25, 1991, p. 5081. [cited by applicant]
Ohtsuka E, Matsuki S, Ikehara M, Takahashi Y, Matsubara K. An alternative approach to deoxyoligonucleotides as hybridization probes by insertion of deoxyinosine at ambiguous codon positions. J Biol Chem. Mar. 10, 1985;2… [cited by applicant]
Rossolini GM, Cresti S, Ingianni A, Cattani P, Riccio ML, Satta G. Use of deoxyinosine-containing primers vs degenerate primers for polymerase chain reaction based on ambiguous sequence information. Mol Cell Probes. Apr… [cited by applicant]
Leicher T, Bähring R, Isbrandt D, Pongs O. Coexpression of the KCNA3B gene product with Kv1.5 leads to a novel A-type potassium channel. J Biol Chem. Dec. 25, 1998;273(52):35095-101. [cited by applicant]
Köhler, G., Milstein, C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256, 495-497 (1975). [cited by applicant]
Kozbor D, Roder JC. The production of monoclonal antibodies from human lymphocytes. Immunol Today. Mar. 1983;4(3):72-9. [cited by applicant]
International Search Report and Written Opinion filed in international application PCT/US21/16104 mailed on Jun. 30, 2021. [cited by applicant]
Marks JD, Griffiths AD, Malmqvist M, Clackson TP, Bye JM, Winter G. By-passing immunization: building high affinity human antibodies by chain shuffling. Biotechnology (N Y). Jul. 1992;10(7):779-83. [cited by applicant]
Lonberg N, Taylor LD, Harding FA, Trounstine M, Higgins KM, Schramm SR, Kuo CC, Mashayekh R, Wymore K, McCabe JG, et al. Antigen-specific human antibodies from mice comprising four distinct genetic modifications. Nature… [cited by applicant]
Morrison, S. Success in specification. Nature 368, 812-813 (1994). [cited by applicant]
Fishwild, D., O'Donnell, S., Bengoechea, T. et al. High-avidity human IgGK monoclonal antibodies from a novel strain of minilocus transgenic mice. Nat Biotechnol 14, 845-851 (1996). [cited by applicant]
Neuberger M. Generating high-avidity human Mabs in mice. Nat Biotechnol. Jul. 1996; 14(7):826. [cited by applicant]
Lonberg N, Huszar D. Human antibodies from transgenic mice. Int Rev Immunol. 1995; 13(1):65-93. [cited by applicant]
Traunecker A, Lanzavecchia A, Karjalainen K. Bispecific single chain molecules (Janusins) target cytotoxic lymphocytes on HIV infected cells. Embo J. Dec. 1991;10(12):3655-9. [cited by applicant]
Suresh MR, Cuello AC, Milstein C. Bispecific monoclonal antibodies from hybrid hybridomas. Methods Enzymol. 1986;121:210-28. [cited by applicant]
Jones PT, Dear PH, Foote J, Neuberger MS, Winter G. Replacing the complementarity-determining regions in a human antibody with those from a mouse. Nature. May 29-Jun. 4, 1986;321(6069):522-5. [cited by applicant]
Riechmann L, Clark M, Waldmann H, Winter G. Reshaping human antibodies for therapy. Nature. Mar. 24, 1988;332(6162):323-7. [cited by applicant]
Verhoeyen M, Milstein C, Winter G. Reshaping human antibodies: grafting an antilysozyme activity. Science. Mar. 25, 1988;239(4847):1534-6. [cited by applicant]
Leonard G. Presta, Antibody engineering, Current Opinion in Structural Biology, vol. 2, Issue 4, 1992, pp. 593-596. [cited by applicant]
Wu AM, Senter PD. Arming antibodies: prospects and challenges for immunoconjugates. Nat Biotechnol. Sep. 2005;23(9):1137-46. [cited by applicant]
Henikoff S, Henikoff JG. Amino acid substitution matrices from protein blocks. Proc Natl Acad Sci U S A. Nov. 15, 1992;89(22):10915-9. [cited by applicant]
International Search Report and Written Opinion in International Application PCT/US2021/016103 Mailed on Apr. 29, 2021. [cited by applicant]