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Anti-KC4 humanized monoclonal antibody and cells that express the antibody |
| RE40535 |
Anti-KC4 humanized monoclonal antibody and cells that express the antibody
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| Patent Drawings: | |
| Inventor: |
Couto, et al. |
| Date Issued: |
October 7, 2008 |
| Application: |
10/144,047 |
| Filed: |
May 14, 2002 |
| Inventors: |
Couto; Fernando J. R. do (Pleasanton, CA)
Ceriani; Roberto L. (Lafayette, CA)
Peterson; Jerry A. (Eureka, CA)
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| Assignee: |
IBC Pharmaceuticals, Inc. (Morris Plains, NJ) |
| Primary Examiner: |
Huff; Sheela J. |
| Assistant Examiner: |
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| Attorney Or Agent: |
Foley & Lardner LLP |
| U.S. Class: |
530/388.85; 424/130.1; 424/133.1; 424/156.1; 424/9.1; 435/328; 435/7.95; 436/518; 530/387.1; 530/387.3; 530/388.8 |
| Field Of Search: |
424/9.1; 424/130.1; 424/133.1; 424/156.1; 530/388.85; 530/388.8; 530/387.1; 530/387.3; 435/7.95; 435/328; 435/7 |
| International Class: |
C07K 16/00; A61K 49/00; C12N 5/16; G01N 33/53 |
| U.S Patent Documents: |
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| Foreign Patent Documents: |
2 188 638 |
| Other References: |
Cruse et al., Illustrated Dictionary of Immunology, CRC Press, p. 144, 1994. cited by examiner.
Freshney (Culture of Animal Cells, A Manual of Basic Technique, Alan R. Liss, Inc., 1983, New York, p. 4 cited by examiner.
Dermer (Bio/Technology, 1994, 12:320. cited by examiner.
Seaver (1994; Genetic Engineering vol. 14(14): pp. 10 and 21. cited by examiner.
Gura (Science, 1997, 278:1041-1042. cited by examiner.
Jain (Sci. Am., 1994, 271:58-65. cited by examiner.
Trickett (Medical Laboratory sciences 47:120-131, 1990. cited by examiner.
Treleaven et al (Hematological Oncology 3:36-75, 1985. cited by examiner.
Morrison et al., Proc. Natl. Acad. Sci, 81:6851-6855, Nov. 1984. cited by other.
E.A. Padlan, Molecular Immunology, 28:4/5:489-498, 1991. cited by other.
J.A. Peterson et al., Biochemical and Histological Characterization of Antigens Preferentially Expressed on the Surface and Cytoplasm of Breast Carcinoma Cells Identified by Monoclonal Antibodies Against the Human Milk Fat Globule, Hybridoma9:221-235, 1990. cited by other.
D. R. Davies and E. A. Padlan, Antibody-Antigen Complexis, Annu. Rev. Biochem, 59:439-73, 1990. cited by other.
L. Reichmann et al., Reshaping Human Antibodies for Therapy, Nature, 332:323-327, 1988. cited by other.
Dienhart, D.G., et al., "Imaging of non-small cell lung cancers with a monoclonal antibody, KC-4G3, which recognizes a human milk fat globule antigen," Cancer Res. 50(21):7068-76 (Nov. 1, 1990) (plus Abstract). cited by other.
Longley, C., et al., "Pharmacokinetics, biodistribution, and gamma camera imaging of .sup.111In-KC-4G3 murine monoclonal antibody in athymic nude mice with or without human tumor xenografts," Cancer Res. 50(18):5954-61 (Sep. 15, 1990). cited byother. |
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| Abstract: |
An anti-KC-4 humanized monoclonal antibody that comprises the variable regions of the light and heavy chains of the anti-KC-4 murine antibody, wherein the light chain has 7 amino acids and the heavy chain has 12 amino acids of the framework regions substituted with amino acid present in equivalent positions in antibodies of a species other than munne, and the constant regions of a human antibody. The antibody may be labeled and/or glycosylated, and is presented as a composition with a carrier. The anti-KC-4 monoclonal antibody is used in diagnostic kits for cancer and in in vivo methods of imaging and treating a primary or metastasized cancer, and in vitro diagnosis and ex vivo purging neoplastic cells from a biological fluid. RNAs and DNAs encode the monoclonal antibody, and a hybrid vector carrying the nucleotides and transfected cells express the peptides. |
| Claim: |
What is claimed as novel in Letters Patent of the United States is:
1. A .[.modified chimeric.]. .Iadd.humanized anti-KC-4 .Iaddend.antibody which selectively binds to the human KC-4 antigen,comprising (1) the .Iadd.humanized .Iaddend.variable regions of the light and heavy chains of an anti-KC-4 murine antibody and (2) light and heavy chain constant regions of a human antibody, wherein the amino acid sequence of the variable regionscomprises SEQ ID NOS: 50 and SEQ ID NO: 51.
.[.2. The antibody of claim 1, wherein 12 amino acids in the light chain framework regions (FRs) are substituted and 7 amino acids in the heavy chain FRs are substituted..].
.[.3. The antibody of claim 2, wherein said amino acids in said framework regions are amino acids present in equivalent positions in antibodies of species other than murine..].
4. An antibody according to claim 1, further comprising at least one glycosyl residue attached thereto.
5. A composition of matter, comprising the antibody of claim 1 and a carrier.
6. A cancer diagnostic kit, comprising the composition of claim 5, wherein said carrier is a pharmaceutically acceptable carrier for in vivo administration, and wherein said antibody is in radiolabeled form.
7. A cancer therapy kit, comprising the composition of claim 4 in a pharmaceutically-acceptable form, wherein said antibody is in radiolabeled form.
8. An in vitro cancer diagnostic kit, comprising the antibody of claim 1; and a solid support.
9. The in vitro kit of claim 8, further comprising one or more heterologous immunoglobulins that selectively bind to the constant region of the anti-KC-4 antibody.
10. The in vitro kit of claim 9, further comprising a label selected from the group consisting of a radioisotope, an enzyme, a phosphorescent molecule, and a fluorescent molecule, wherein said label is conjugated to said antibody of saidimmunoglobulin.
11. A .[.hybridoma.]. cell expressing the antibody of claim 1.
12. The .[.hybridoma.]. cell of claim 11, having the ATCC Accession No. HB 11455 (HuKC4V2).
13. A composition, comprising the .[.hybridoma.]. cell of claim 11, and a diluent or a carrier.
.Iadd.14. A method of determining the presence of cancer cells in a tissue or a blood sample thereof, comprising contacting a tissue or a blood sample with the anti-KC-4 antibody of claim 1 or an antigen binding fragment thereof, and detectingthe presence of an immune complex formed between said anti-KC-4 antibody and the KC-4 antigen of said tissue or said blood sample thereof..Iaddend.
.Iadd.15. A method according to claim 14, wherein the tissue is excised from a subject prior to being contacted with the anti-KC-4 antibody, and wherein said contacting and detecting steps are carried out in vitro..Iaddend.
.Iadd.16. A method according to claim 15, further comprising comparing results obtained by analyzing said formed complexes with a standard cut-off value determined by comparing results obtained for normal and cancer patients' samples wherein aresult above a cut-off value is indicative of cancer..Iaddend.
.Iadd.17. A method of imaging a cancer, comprising administering a pharmaceutically-acceptable composition comprising an effective imaging amount of the anti-KC-4 antibody of claim 1 or an antigen binding fragment thereof, in radiolabeled form,to a subject suspected of having a primary or metastasized cancer; and detecting any binding of the labeled antibody to cancer cells in the subject by external imaging..Iaddend.
.Iadd.18. A method of treating cancer in a subject, comprising administering to a subject in need of treatment an effective therapeutic amount of the antibody of claim 1, wherein the antibody is conjugated to a therapeutic agent..Iaddend.
.Iadd.19. A method of purging cancer cells from a biological sample, comprising contacting a biological sample obtained from a subject suspected of having cancer with the antibody of claim 1 and allowing said antibody to bind the KC-4 antigenassociated with cancer cells in the sample to form an immune complex between said antibody and the antigen of said biological sample; and removing said immune complex from the biological sample..Iaddend.
.Iadd.20. A method according to claim 14, wherein said tissue sample is prepared for immunohistochemical analysis..Iaddend.
.Iadd.21. A method of purging cancer cells from a biological sample and replenishing the purged sample to a subject, comprising the method of claim 19, wherein said method further comprises reintroducing the purged biological sample to thesubject..Iaddend. |
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