Antibodies against claudin 18.2 useful in cancer diagnosis
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A61K-049/00
C07K-016/00
C07K-016/18
C07K-016/28
C07K-016/30
G01N-001/00
G01N-033/574
A61K-051/10
출원번호
US-0227565
(2016-08-03)
등록번호
US-10053512
(2018-08-21)
우선권정보
EP-PCT/EP2012/001991 (2012-05-09)
발명자
/ 주소
Sahin, Ugur
Tureci, Ozlem
Mitnacht-Kraus, Rita
Woll, Stefan
출원인 / 주소
GANYMED PHARMACEUTICALS AG
대리인 / 주소
Neal, Gerber & Eisenberg LLP
인용정보
피인용 횟수 :
0인용 특허 :
93
초록
The invention relates to antibodies directed against an epitope located within the C-terminal portion of CLDN18.2 which are useful, for example, in diagnosing cancer and/or in determining whether cancer cells express CLDN18.2.
대표청구항▼
1. An antibody or antigen binding fragment thereof that binds to claudin 18.2 (CLDN18.2) or a peptide having the amino acid sequence TEDEVQSYPSKHDYV (SEQ ID NO: 5) or EVQSYPSKHDYV (SEQ ID NO: 6) wherein the antibody or antigen-binding fragment comprises(i) an antibody heavy chain comprising: a CDR1
1. An antibody or antigen binding fragment thereof that binds to claudin 18.2 (CLDN18.2) or a peptide having the amino acid sequence TEDEVQSYPSKHDYV (SEQ ID NO: 5) or EVQSYPSKHDYV (SEQ ID NO: 6) wherein the antibody or antigen-binding fragment comprises(i) an antibody heavy chain comprising: a CDR1 having the amino acid sequence set forth in SEQ ID NO: 8,a CDR2 having the amino acid sequence set forth in SEQ ID NO: 9, anda CDR3 having the amino acid sequence set forth in SEQ ID NO: 10; andan antibody light chain comprising: a CDR1 having the amino acid sequence set forth in SEQ ID NO: 12,a CDR2 having the amino acid sequence set forth in SEQ ID NO: 13, anda CDR3 having the amino acid sequence set forth in SEQ ID NO: 14; or(ii) an antibody heavy chain comprising: a CDR1 having the amino acid sequence set forth in SEQ ID NO: 16,a CDR2 having the amino acid sequence set forth in SEQ ID NO: 17, anda CDR3 having the amino acid sequence set forth in SEQ ID NO: 18; andan antibody light chain comprising: a CDR1 having the amino acid sequence set forth in SEQ ID NO: 20,a CDR2 having the amino acid sequence set forth in SEQ ID NO: 21, anda CDR3 having the amino acid sequence set forth in SEQ ID NO: 22. 2. The antibody or antigen-binding fragment thereof of claim 1, wherein said CLDN18.2 is cell surface membrane-bound CLDN18.2. 3. The antibody or antigen-binding fragment thereof of claim 1, wherein said CLDN18.2 is present on cancer cells. 4. The antibody or antigen-binding fragment thereof of claim 3, wherein said cancer cells are CLDN18.2 expressing cancer cells. 5. The antibody or antigen-binding fragment thereof of claim 3, wherein said cancer cells are selected from the group consisting of gastric, esophageal, pancreatic, lung, ovarian, colon, hepatic, head-neck, and gallbladder cancer cells. 6. The antibody or antigen-binding fragment thereof of claim 1, wherein the antibody or antigen-binding fragment thereof does not bind to non-cancerous cells except stomach epithelial cells. 7. The antibody or antigen-binding fragment thereof of claim 1, wherein the antibody or antigen-binding fragment thereof does not bind to non-cancerous lung cells. 8. The antibody of claim 1, wherein the antibody is a chimeric, human or humanized antibody. 9. The antibody of claim 1, wherein the antibody is a monoclonal antibody. 10. A conjugate comprising an antibody or antigen-binding fragment of claim 1 coupled to at least one detectable label. 11. A hybridoma capable of producing the antibody of claim 1. 12. The antibody or antigen-binding fragment of claim 1, wherein said CLDN18.2 comprises the amino acid sequence according to SEQ ID NO: 2 of the sequence listing or a variant of said amino acid sequence. 13. The antibody or antigen-binding fragment of claim 1, wherein the antibody or antigen-binding fragment comprises an antibody heavy chain comprising: a CDR1 having the amino acid sequence set forth in SEQ ID NO: 16,a CDR2 having the amino acid sequence set forth in SEQ ID NO: 17, anda CDR3 having the amino acid sequence set forth in SEQ ID NO: 18; andan antibody light chain comprising: a CDR1 having the amino acid sequence set forth in SEQ ID NO: 20,a CDR2 having the amino acid sequence set forth in SEQ ID NO: 21, anda CDR3 having the amino acid sequence set forth in SEQ ID NO: 22. 14. The antibody or antigen-binding fragment of claim 1, wherein the antibody or antigen-binding fragment comprises an antibody heavy chain comprising: a CDR1 having the amino acid sequence set forth in SEQ ID NO: 8,a CDR2 having the amino acid sequence set forth in SEQ ID NO: 9, anda CDR3 having the amino acid sequence set forth in SEQ ID NO: 10; andan antibody light chain comprising: a CDR1 having the amino acid sequence set forth in SEQ ID NO: 12,a CDR2 having the amino acid sequence set forth in SEQ ID NO: 13, anda CDR3 having the amino acid sequence set forth in SEQ ID NO: 14. 15. The antibody or antigen-binding fragment of claim 13, wherein the antibody or antigen-binding fragment comprises an antibody heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 15, and an antibody light chain comprising the amino acid sequence set forth in SEQ ID NO: 19. 16. The antibody or antigen-binding fragment of claim 14, wherein the antibody or antigen-binding fragment comprises an antibody heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 7, and an antibody light chain comprising the amino acid sequence set forth in SEQ ID NO: 11. 17. A diagnostic test kit which comprises the antibody or antigen-binding fragment of claim 1. 18. A method for detecting CLDN18.2 or determining the quantity of CLDN18.2 in a sample comprising the steps of: (i) contacting a sample with the antibody or antigen-binding fragment of claim 1 and(ii) detecting the formation of a complex or determining the quantity of a complex between the antibody or the antigen-binding fragment and CLDN18.2. 19. A method for determining whether cells express CLDN18.2 comprising the steps of: (i) contacting a cellular sample with the antibody or antigen-binding fragment of claim 1 and(ii) detecting the formation of a complex between the antibody or the antigen-binding fragment and CLDN18.2 expressed by cells in said sample. 20. A method for diagnosis, detection or monitoring of cancer comprising the steps of: contacting a biological sample with the antibody or antigen-binding fragment of claim 1 and(ii) detecting the formation of a complex and/or determining the quantity of a complex between the antibody or the antigen-binding fragment and CLDN18.2. 21. A method for determining whether a cancer is treatable by a cancer therapy targeting CLDN18.2 comprising the steps of: (i) contacting a sample comprising cancer cells with the antibody or antigen-binding fragment of claim 1 and(ii) detecting the formation of a complex between the antibody or the antigen-binding fragment and CLDN18.2. 22. The method of claim 18, wherein the sample comprises a paraffin embedded tissue section fixed with paraformaldehyde. 23. The method of claim 18, wherein, in step (i), the antibody or antigen binding fragment is at a concentration of about 0.1 to about 0.5 μg/ml. 24. The method of claim 23, wherein the concentration is about 0.2 μg/ml. 25. The method of claim 18, wherein step (i) comprises incubating the sample with the antibody or antigen-binding fragment overnight at 4° C. 26. The method of claim 18, wherein the antibody or antigen binding fragment is labeled with a detectable label. 27. The method of claim 26, wherein the detectable label is an enzyme or a fluorophore. 28. The method of claim 18, wherein the method further comprises contacting the antibody or antigen-binding fragment with a secondary antibody, wherein the secondary antibody is labeled with a detectable label. 29. The method of claim 28, wherein the secondary antibody is a horseradish-peroxidase (HRP)-labeled secondary antibody. 30. The method of claim 29, wherein step (ii) comprises exposing the HRP-labeled secondary antibody to a chemiluminescent substrate. 31. The method of claim 18, wherein the antibody or antigen-binding fragment comprises an antibody heavy chain comprising: a CDR1 having the amino acid sequence set forth in SEQ ID NO: 8,a CDR2 having the amino acid sequence set forth in SEQ ID NO: 9, anda CDR3 having the amino acid sequence set forth in SEQ ID NO: 10; andan antibody light chain comprising: a CDR1 having the amino acid sequence set forth in SEQ ID NO: 12,a CDR2 having the amino acid sequence set forth in SEQ ID NO: 13, anda CDR3 having the amino acid sequence set forth in SEQ ID NO: 14. 32. The method of claim 18, wherein the antibody or antigen-binding fragment comprises an antibody heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 7, and an antibody light chain comprising the amino acid sequence set forth in SEQ ID NO: 11. 33. The method of claim 18, wherein the antibody or antigen-binding fragment comprises an antibody heavy chain comprising: a CDR1 having the amino acid sequence set forth in SEQ ID NO: 16,a CDR2 having the amino acid sequence set forth in SEQ ID NO: 17, anda CDR3 having the amino acid sequence set forth in SEQ ID NO: 18; andan antibody light chain comprising: a CDR1 having the amino acid sequence set forth in SEQ ID NO: 20,a CDR2 having the amino acid sequence set forth in SEQ ID NO: 21, anda CDR3 having the amino acid sequence set forth in SEQ ID NO: 22. 34. The method of claim 18, wherein the antibody or antigen-binding fragment comprises an antibody heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 15, and an antibody light chain comprising the amino acid sequence set forth in SEQ ID NO: 19.
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