Compounds that bind to p185 and methods of using the same
View Patent ↗Novels peptides and pharmaceutical compositions comprising the same are disclosed. Conjugated compositions peptides linked to detectable agents and/or cytotoxic agents. are disclosed. Method of detecting tumors that have p185 on tumor cell surfaces are disclosed. Methods of preventing transformation of a normal cell into a tumor cell in an individual at risk of developing a tumor having tumor cells which have p185 on their surfaces are disclosed. Methods of treating an individual who has cancer characterized by tumor cells that have a p185 on their cell surfaces are disclosed.
1. An isolated peptide an amino acid sequence selected from the group consisting of:
YCDGFYACYMDV (SEQ ID NO:113);
FCDGFYACYKDV (SEQ ID NO:128);
dFCDGFYAGdYMDVK (SEQ ID NO:124);
GdFCDGFYACdYMDVK (SEQ ID NO:125);
GGdFCDGFYACdYMDVK (SEQ ID NO:126);
GGGdFCDGFYACdYMDVK (SEQ ID NO:127); and
dFCDGFYACDYMDV (SEQ ID NO:118).
2. A pharmaceutical composition comprising a peptide according to claim 1 , and a pharmaceutically acceptable carrier or diluent.
3. A method of treating an individual who has cancer characterized by tumor cells that have a p185 on their cell surfaces comprising the steps of a) identifying said individual; b) administering to said individual, a therapeutically effective amount of a peptide having an amino acid sequence selected from the group consisting of:
YCDGFYACYMDV (SEQ ID NO: 113);
FCDGFYACYKDV (SEQ ID NO: 128);
dFCDGFYACdYMDVK (SEQ ID NO: 124);
GdFcDGFYACdYMDVK (SEQ ID NO: 125);
GGdFCDGFYACdYMDVK (SEQ ID NO: 126);
GGGdFCDGFYACdYMDVK (SEQ ID NO: 127); and
dFCDGFYACDYMDV (SEQ ID NO: 118)
in combination with a detectable agent and/or cytotoxic agent.
4. A composition comprising a conjugate of peptide linked to a detectable agent and/or cytotoxic agent, wherein the peptide has an amino acid sequence selected from the group consisting of:
YCDGFYACYMDV (SEQ ID NO:113);
FCDGFYACYKDV (SEQ ID NO:128);
dFCDGFYACdYMDVK (SEQ ID NO:124);
GdFCDGFYACdYMDVK (SEQ ID NO:125);
GGdFCDGFYACdYMDVK (SEQ ID NO:126);
GGGdFCDGFYACdYMDVK (SEQ ID NO:127); and
dFCDGFYACDYMDV (SEQ ID NO:118).
5. The composition of claim 4 wherein the peptide is linked to the detectable agent and/or the cytotoxic agent by a chelating linker.
6. The composition of claim 5 wherein the chelating linker is DOTA/DTPA.
7. The composition of claim 5 wherein said peptide is linked to a detectable agent.
8. The composition of claim 7 wherein said detectable agent is a radiosotope.
9. The composition of claim 8 wherein said radioisotope is selected from the group consisting of 99mTc, Y90, and 18F.
10. A method of detecting a tumor that has p185on tumor cell surfaces comprising the step of administering, to an individual suspected of having such a tumor or being susceptible to such a tumor, a composition comprising a conjugate of peptide linked to a detectable agent and/or cytotoxic agent, wherein the peptide has an amino acid sequence selected from the group consisting of:
YCDGFYACYMDV (SEQ ID NO: 113);
FCDGFYACYKDV (SEQ ID NO: 128);
dFCDGFYACdYMDVK (SEQ ID NO: 124);
GdFcDGFYACdYMDVK (SEQ ID NO: 125);
GGdFCDGFYACdYMDVK (SEQ ID NO: 126);
GGGdFCDGFYACdYMDVK (SEQ ID NO: 127); and
dFCDGFYACDYMDV (SEQ ID NO: 118) and detecting the presence of said conjugate, localized within the body of said individual.
11. The composition of claim 5 , wherein said peptide is linked to a cytotoxic agent selected from the group consisting of: cytotoxic drugs, toxins and cytostatic drugs.
12. A pharmaceutical composition comprising a conjugated compound according to claim 4 , and a pharmaceutically acceptable carrier or diluent.
13. A method of treating an individual who has cancer characterized by tumor cells that have a p185on their cell surfaces comprising the steps of:
a) identifying said individual;
b) administering to said individual, a therapeutically effective amount of composition comprising a conjugate of peptide linked to a detectable agent and/or cytotoxic agent, wherein the peptide has an amino acid sequence selected from the group consisting of:
YCDGFYACYMDV (SEQ ID NO: 113);
FCDGFYACYKDV (SEQ ID NO: 128);
dFCDGFYACdYMDVK (SEQ ID NO: 124);
GdFcDGFYACdYMDVK (SEQ ID NO: 125);
GGdFCDGFYACdYMDVK (SEQ ID NO: 126);
GGGdFCDGFYACdYMDVK (SEQ ID NO: 127); and
dFCDGFYACDYMDV (SEQ ID NO: 118).
14. The peptide of claim 1 wherein said peptide has the amino acid sequence:
YCDGFYACYMDV (SEQ ID NO:113).
15. The peptide of claim 1 wherein said peptide has the amino acid sequence:
FCDGFYACYKDV (SEQ ID NO:128).
16. The peptide of claim 1 wherein said peptide has the amino acid sequence:
dFCDGFYACdYMDVK (SEQ ID NO:124).
17. The peptide of claim 1 wherein said peptide has the amino acid sequence:
GdFCDGFYACdYMDVK (SEQ ID NO:125).
18. The peptide of claim 1 wherein said peptide has the amino acid sequence:
GGdFCDGFYACdYMDVK (SEQ ID NO:126).
19. The peptide of claim 1 wherein said peptide has the amino acid sequence:
GGGdFCDGFYACdYMDVK (SEQ ID NO:127).
20. The peptide of claim 1 wherein said peptide has the amino acid sequence:
dFCDGFYACDYMDV (SEQ ID NO:118).
21. The peptide according to any one of claims 15 and 16 - 20 wherein the carboxy terminus is amidated.
22. The peptide according to any one of claims 15 and 16 - 20 wherein the carboxy terminus is hydroxylated.