# US 11,111,305 B2 · Method of using a bispecific antibody to conditionally inhibit a receptor signaling complex

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- Number: US 11,111,305 B2
- Document ID: US11111305B2
- Status: Granted
- Kind: B2
- Application number: 16/475,342
- Filed: 2018-01-09
- Published: 2019-11-14
- Granted: 2021-09-07
- Earliest claimed: 2017-01-09
- Assignees: Torch Therapeutics
- Applicants: Torch Therapeutics
- Inventors: Todd M. Kinsella; Donald G. Payan; Ramesh Bhatt; Kristen Baltgalvis
- Web page: https://patentgrep.com/patent/US11111305B2

## CPC

- C07K 16/2863: {against receptors for growth factors, growth regulators}
- C07K 16/00: Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K 16/289: {against CD45}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/31: multispecific
- C07K 2317/70: characterized by effect upon binding to a cell or to an antigen
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

This invention describes the design of bispecific antibodies that function as conditionally effective therapeutics by binding to a functionally silent epitope on one component of a targeted signaling complex and simultaneously binding to a second protein, whose expression or accessibility is cell- or disease environment-specific, and whose antibody-driven proximity to the signaling complex leads to an alteration of signal transduction.

## Claims

### Claim 1

A method of conditionally inhibiting a receptor signaling complex (RSC) comprising a receptor protein and a receptor ligand in a target cell comprising:
a) providing a cell capable of forming said receptor signaling complex, wherein said receptor protein binds said ligand at an active site;
b) contacting said cell with a bispecific antibody comprising:
i) a first antigen binding domain that binds to said receptor protein at a first epitope outside of said active site;
ii) a second antigen binding domain that binds to a target protein;
c) wherein if said cell expresses said target protein, said first antigen binding domain binds to said receptor protein and said second antigen binding domain binds to said target protein, thereby inhibiting the binding of said receptor protein and said ligand to reduce signaling; and
d) wherein if said cell does not express said target protein, said first antigen binding domain binds to said receptor protein and does not prevent binding of said ligand to said receptor protein to achieve receptor signaling, and
e) and wherein said receptor protein/target protein pair is selected from the group consisting of Type II Receptor for TGFβ (TGFBR2)/CD45, TGFBR2/Fibroblast Activation Protein (FAP), TGFBR2/Beta-3 Adrenergic Receptor (ADRB3), Colony Stimulating Factor 2 Receptor Alpha Subunit (GMCSFRα)/CD33, Signal-Regulatory Protein Alpha (SIRPα)/Programmed death-ligand 1 (PD-L1), Interleukin 2 Receptor (IL2R)/Layilin (LAYN), Program cell death protein 1 (PD-1)/Potassium Calcium-Activated Channel Subfamily M Alpha 1 (KCNMA1) and Glycoprotein 130 (gp130)/PD-L1.