Antibodies and related molecules that bind to PSCA proteins

• US 7,541,442 B2
• Filed: 02/15/2006
• Issued: 06/02/2009
• Est. Priority Date: 05/30/2003
• Status: Active Grant

• Current Assignee: Agensys, Inc. (Astellas Pharma Incorporated)
• Original Assignee: Agensys, Inc. (Astellas Pharma Incorporated)
• Inventors: Gudas, Jean, Raitano, Arthur B., Morrison, Robert Kendall, Challita-Eid, Pia M., Jakobovits, Aya, Jia, Xiao-chi
• Primary Examiner(s): Canella; Karen A
• Assistant Examiner(s): Reddig; Peter J
• Application Number:
  US11/355,464
• Publication Number:
  US 20060147375A1
• Time in Patent Office: 1,203 Days
• Field of Search: None
• US Class Current: 530/388.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/53 DNA (RNA) vaccination
• CPC Class Codes: A61K 39/001193 Prostate associated antigens e.g. Prostate stem cell antigen [PSCA]; Prostate carcinoma tumor antigen [PCTA]; PAP or PSGR
• CPC Class Codes: A61K 47/6869 the tumour determinant being from a cell of the reproductive system: ovaria, uterus, testes, prostate
• CPC Class Codes: A61K 49/0002 General or multifunctional contrast agents, e.g. chelated agents
• CPC Class Codes: A61K 51/1051 the tumor cell being from breast, e.g. the antibody being herceptin
• CPC Class Codes: A61K 51/1054 the tumor cell being from lung
• CPC Class Codes: A61K 51/1057 the tumor cell being from liver or pancreas
• CPC Class Codes: A61K 51/106 the tumor cell being from kidney or bladder
• CPC Class Codes: A61K 51/1072 the tumor cell being from the reproductive system, e.g. ovaria, uterus, testes or prostate
• CPC Class Codes: C07K 14/4748 Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE
• CPC Class Codes: C07K 14/705 Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748
• CPC Class Codes: C07K 16/30 from tumour cells
• CPC Class Codes: C07K 16/3069 Reproductive system, e.g. ovaria, uterus, testes, prostate
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2317/732 Antibody-dependent cellular cytotoxicity [ADCC]
• CPC Class Codes: C07K 2317/734 Complement-dependent cytotoxicity [CDC]
• CPC Class Codes: C07K 2317/77 Internalization into the cell
• CPC Class Codes: G01N 2500/04 Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A)
• CPC Class Codes: G01N 33/566 : using specific carrier or receptor proteins as ligand binding reagents where possible specific carrier or receptor proteins are classified with their target compounds
• CPC Class Codes: G01N 33/57415 : of breast
• CPC Class Codes: G01N 33/57434 : of prostate
• CPC Class Codes: G01N 33/57484 : involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
• CPC Class Codes: G01N 33/57492 : involving compounds localized on the membrane of tumor or cancer cells

Abstract

Antibodies and molecules derived therefrom that bind to novel PSCA protein, and variants thereof, are described wherein PSCA exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in the cancers listed in Table I. Consequently, PSCA provides a diagnostic, prognostic, prophylactic and/or therapeutic target for cancer. The PSCA gene or fragment thereof, or its encoded protein, or variants thereof, or a fragment thereof, can be used to elicit a humoral or cellular immune response; antibodies or T cells reactive with PSCA can be used in active or passive immunization.

Claims

1. A monoclonal antibody comprising an antigen binding site that binds specifically to a PSCA protein comprising the amino acid sequence of SEQ ID NO:

2, wherein the monoclonal antibody comprises the amino acid sequence of the variable heavy chain region and the variable light chain region of the antibody secreted by the hybridoma assigned A.T.C.C. Accession No.;

PTA-6697.

4. The antibody of claim 1, wherein the antibody is a fully human antibody.

5. The antibody of claim 1, wherein the antibody is coupled to a detectable marker, a toxin, a therapeutic agent, or a chemotherapeutic agent.

6. The antibody of claim 5, wherein the detectable marker is a radioisotope, a metal chelator, an enzyme, a fluorescent compound, a bioluminescent compound or a chemiluminescent compound.

7. The antibody of claim 6, wherein the radioisotope comprises ²¹²Bi, ¹³¹I, ¹³¹In, ⁹⁰Y, ¹⁸⁶Re, ²¹¹At, ¹²⁵I, ¹⁸⁸Re, ¹⁵³Sm, ²¹³Bi, ³²P, or Lu.

8. The antibody of claim 5, wherein the toxin comprises ricin, ricin A chain, doxorubicin, daunorubicin, a maytansinoid, taxol, ethidium bromide, mitomycin, etoposide, tenoposide, vincristine, vinblastine, colchicine, dihydroxy anthracin dione, actinomycin, diphtheria toxin, Pseudomonas exotoxin (PE) A, PE40, abrin, abrin A chain, modeccin A chain, alpha sarcin, gelonin, mitogellin, retstrictocin, phenomycin, enomycin, curicin, crotin, calicheamicin, sapaonaria officinalis inhibitor, glucocorticoid, auristatin, auromycin, yttrium, bismuth, combrestatin, duocarmycins, dolostatin, cc 1065, or a cisplatin.

9. A hybridoma that produces the monoclonal antibody of claim 1.

10. A pharmaceutical composition that comprises the antibody of claim 1 in a unit dose form.

11. An assay for detecting the presence of a PSCA protein comprising the amino acid sequence of SEQ ID NO:

2 in a biological sample comprising contacting the sample with the monoclonal antibody of claim 1, and detecting the binding of the PSCA protein in the sample, wherein the protein comprises the amino acid sequence of SEQ ID NO;

2.

12. The assay of claim 11, wherein the antibody is labeled with a detectable marker.

13. A method for detecting a PSCA protein comprising the amino acid sequence of SEQ ID NO:

2 in a biological sample, comprising steps of;

providing the biological sample and a control sample;

contacting the biological sample and the control sample with the antibody of claim 1 that specifically binds to the PSCA protein, wherein the protein comprises the amino acid sequence of SEQ ID NO;

2; and

determining an amount of a complex of the substance with the PSCA protein comprising the amino acid sequence of SEQ ID NO;

2 and the antibody present in the biological sample and the control sample.

14. The method of claim 13 further comprising:

taking the biological sample and the control sample from a patient who has or is suspected of having a cancer listed in Table I.

2. A monoclonal antibody fragment comprising an antigen binding site that binds specifically to a PSCA protein comprising the amino acid sequence of SEQ ID NO:

2, wherein the monoclonal antibody fragment comprises the amino acid sequence of the variable heavy chain region and the variable light chain region of the monoclonal antibody secreted by the hybridoma assigned A.T.C.C. Accession No.;

PTA-6697.

3. The antibody fragment of claim 2, wherein the fragment is an Fab, F(ab′

)₂, Fv or Sfv fragment.

15. The antibody fragment of claim 2 wherein the antibody fragment is coupled to a detectable marker, a toxin, a therapeutic agent, or a chemotherapeutic agent.

16. The antibody fragment of claim 15, wherein the detectable marker is a radioisotope, a metal chelator, an enzyme, a fluorescent compound, a bioluminescent compound or a chemiluminescent compound.

17. The antibody fragment of claim 16, wherein the radioisotope comprises ²¹²Bi, ¹³¹I, ¹³¹In, ⁹⁰Y, ¹⁸⁶Re, ²¹¹At, ¹²⁵I, ¹⁸⁸Re, ¹⁵³Sm, ²¹³Bi, ³²P, or Lu.

18. The antibody fragment of claim 15, wherein the toxin comprises ricin, ricin A chain, doxorubicin, daunorubicin, a maytansinoid, taxol, ethidium bromide, mitomycin, etoposide, tenoposide, vincristine, vinbiastine, colchicine, dihydroxy anthracin dione, actinomycin, diphtheria toxih, Pseudomonas exotoxin (PE) A, PE40, abrin, abrin A chain, modeccin A chain, alpha sarcin, gelonin, mitogellin, retstrictocin, phenomycin, enomycin, curicin, crotin, calicheamicin, sapaonaria officinalis inhibitor, glucocorticoid, auristatin, auromycin, yttrium, bismuth, combrestatin, duocarmycins, dolostatin, cc 1065, or a cisplatin.

19. A pharmaceutical composition that comprises the monoclonal antibody fragment of claim 2 in a unit dose form.