# US 8,772,459 B2 · J591 minibodies and Cys-diabodies for targeting human prostate specific membrane antigen (PSMA) and methods for their use > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 8,772,459 B2 - Document ID: US8772459B2 - Status: Granted - Kind: B2 - Application number: 12/959,340 - Filed: 2010-12-02 - Published: 2011-11-03 - Granted: 2014-07-08 - Earliest claimed: 2009-12-02 - Assignees: Imaginab, Inc. - Applicants: David Ho; Tove Olafsen; Arye Lipman - Inventors: David Ho; Tove Olafsen; Arye Lipman - Web page: https://patentgrep.com/patent/US8772459B2 ## CPC - C07K 16/3069: {Reproductive system, e.g. ovaria, uterus, testes, prostate} - A61K 51/1072: {the tumor cell being from the reproductive system, e.g. ovaria, uterus, testes or prostate} - A61P 35/00: Antineoplastic agents - A61K 2039/505: {comprising antibodies} - C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered - C07K 2317/526: CH3 domain - C07K 2317/56: variable (Fv) region, i.e. VH and/or VL - C07K 2317/622: Single chain antibody (scFv) - C07K 2317/64: comprising a combination of variable region and constant region components - C07K 2317/77: Internalization into the cell - C07K 2317/90: characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract In one embodiment, a minibody monomer that binds PSMA is provided. The minibody monomer is encoded by a nucleotide sequence comprising, from N-terminus to C-terminus, an scFv sequence that can bind PSMA, an artificial hinge sequence, and a human IgG CH3 sequence. In another embodiment, a CysDB monomer that binds PSMA is provided. The CysDB monomer may be encoded by a nucleotide sequence comprising, from N-terminus to C-terminus, an scFv sequence that can bind PSMA and a cysteine tail. In other embodiments, methods for diagnosing or treating a cancer associated with PSMA expression in a subject are provided. ## Claims ### Claim 1 A minibody comprising: an scFv sequence that can bind prostate specific membrane antigen (PSMA), the scFv comprising a variable heavy domain (VH) linked to a variable light domain (VL) by a linker sequence; an artificial hinge sequence; and a human IgG CH3 sequence, wherein the minibody comprises: a heavy chain CDR1 that is a CDR1 in SEQ ID NO: 10; a heavy chain CDR2 that is a CDR2 in SEQ ID NO: 10; a heavy chain CDR3 that is a CDR3 in SEQ ID NO: 10; a light chain CDR1 that is a CDR1 in SEQ ID NO: 10; a light chain CDR2 that is a CDR2 in SEQ ID NO: 10; and a light chain CDR3 that is a CDR3 in SEQ ID NO: 10. ### Claim 2 (depends on 1) The minibody of claim 1, further comprising an N-terminus signal sequence to enable secretion of the minibody when expressed in a cell. ### Claim 3 (depends on 1) The minibody of claim 1, wherein the scFv is in a VHVL orientation such that the VH is upstream of the VL. ### Claim 4 (depends on 3) The minibody of claim 3, wherein the minibody is encoded by a nucleotide sequence that comprises SEQ ID NO:1. ### Claim 5 (depends on 1) The minibody of claim 1, wherein the scFv is in a VLVH orientation such that the VL is upstream of the VH. ### Claim 6 (depends on 1) The minibody of claim 1, wherein the minibody is encoded by a nucleotide sequence, that when expressed by a cell, produces an amino acid sequence, and wherein the amino acid sequence comprises SEQ ID NO:10. ### Claim 7 (depends on 1) The minibody of claim 1, wherein the variable light domain comprises the variable light domain amino acid sequence in SEQ ID NO: 10. ### Claim 8 (depends on 1) The minibody of claim 1, wherein the variable heavy domain comprises the variable heavy domain amino acid sequence in SEQ ID NO: 10. ### Claim 9 (depends on 1) The minibody of claim 1, wherein the variable light domain comprises the variable light domain amino acid sequence in SEQ ID NO: 10, and wherein the variable heavy domain comprises the variable heavy domain amino acid sequence in SEQ ID NO: 10. ### Claim 10 (depends on 1) The minibody of claim 1, wherein the minibody comprises the amino acid sequence of SEQ ID NO: 10. ### Claim 11 (depends on 1) The minibody of claim 1, wherein the minibody is conjugated to at least one therapeutic agent. ### Claim 12 (depends on 11) The minibody of claim 11, wherein the at least one therapeutic agent is selected from the group consisting of a chemotherapeutic agent, a therapeutic antibody, an antibody fragment, a toxin, a radioisotope, an enzyme, a nuclease, a hormone, an immunomodulator, an antisense oligonucleotide, a chelator, a boron compound, a photoactive agent, and a photoactive dye. ### Claim 13 (depends on 1) The minibody of claim 1, wherein the minibody is conjugated to at least one diagnostic agent. ### Claim 14 (depends on 13) The minibody of claim 13, wherein the diagnostic agent is selected from the group consisting of a radioactive substance, a dye, a contrast agent, a fluorescent compound, a fluorescent molecule, a bioluminescent compound, a bioluminescent molecule, an enzyme, an enhancing agent, a quantum dot, and a metal nanoparticle. ### Claim 15 An isolated polynucleotide that encodes a monomer of an anti-PSMA minibody, wherein the polynucleotide comprises SEQ ID NO: 1. ### Claim 16 (depends on 1) The minibody of claim 1, wherein the minibody comprises an amino acid sequence that comprises SEQ ID NO:10. ### Claim 17 (depends on 1) The minibody of claim 1, wherein the minibody comprises: a variable heavy domain of the variable heavy domain in SEQ ID NO:10; and a variable light domain of the variable light domain in SEQ ID NO: 10. ### Claim 18 (depends on 13) The minibody of claim 13, wherein the minibody is conjugated to at least one therapeutic agent.