Claims for Patent: 9,650,416

Summary for Patent: 9,650,416

Title:	.alpha.v.beta.6 peptide ligands and their uses
Abstract:	AV.beta.6 peptide ligands, functional variants thereof and their nucleic acids encoding them are disclosed with their uses in the treatment and imaging of AV.beta.6 mediated diseases.
Inventor(s):	Howard; Mark J. (Kent, GB), Dicara; Danielle (San Francisco, CA), Marshall; John (London, GB)
Assignee:	Cancer Research Technology Limited (London, GB)
Application Number:	14/567,274
Patent Claims:	1. A method of treating a cancer in a patient, wherein cells of said cancer overexpress .alpha.v.beta.6, the method comprising administering to a patient in need thereof, a therapeutically effective amount of a peptide or a peptide linked to a therapeutically active moiety, said peptide or linked peptide comprising the sequence motif B.sub.nRGDLX.sup.5X.sup.6LX.sup.8X.sup.9X.sup.10Z.sub.mX.sub.i or B.sub.nRGDLX.sup.5X.sup.6IX.sup.8X.sup.9X.sup.10Z.sub.mX.sub.i, wherein B.sub.n is a sequence of n amino acids each of which is any D- or L-amino acid, X.sup.5, X.sup.6, X.sup.8, X.sup.9, and X.sup.10 each independently represent any amino acid, Z.sub.m is a sequence of m amino acids independently selected from the group consisting of: Glu, Ala, Leu, Met, Gln, Lys, Arg, Val, Ile, Trp, Phe and Asp, X.sub.i is a sequence of i amino acids each of which is any amino acid, n is 6 to 7, m is at least 1, and n, m, and i are selected to make the maximum length of said peptide 20 amino acids, and wherein said therapeutically active moiety is selected from the group consisting of: mechlorethamine, cyclophosphamide, ifosfamide, melphalan, chlorambucil, hexamethylmelamine, thiotepa, busulfan, carmustine, lomustine, semustine, streptozoein, decarbazine dimethyltriazenoimidazolecarboxamide, methotrexate, fluorouracil, floxuridine, cytarabine, mercaptopurine, thioguanine, pentostatin, vinblastine, vincristine, etoposide, teniposide, dactinomycin, daunorabicin, doxorubicin, bleomycin, plicamycin, mitomycin, L-asparaginase, interferon alphenomes, cisplatin, carboplatin, mitoxantrone and antbracycline, hydroxyurea, procarbazine, mitotane, aminoglutethimide, taxol, flutamide, tamoxifen, ricin, abrin, Pseudomonas exotoxin, tissue factor, TNF.alpha., IL-2, phosphorus-32, iodine-125, iodine-131, indium-111, rhenium-186, rhenium-188, and yttrium-90. 2. A method of diagnosing a cancer in a patient, wherein cells of said cancer overexpress .alpha.v.beta.6, the method comprising: detecting whether .alpha.v.beta.6 integrin is present at a tumor by contacting at least one tumor cell with a peptide comprising the sequence motif B.sub.nRGDLX.sup.5X.sup.6LX.sup.8X.sup.9X.sup.10Z.sub.mX.sub.i or B.sub.nRGDLX.sup.5X.sup.6IX.sup.8X.sup.9X.sup.10Z.sub.mX.sub.i, wherein B.sub.n is a sequence of n amino acids each of which is any D- or L-amino acid, X.sup.5, X.sup.6, X.sup.8, X.sup.9, and X.sup.10 each independently represent any amino acid, Z.sub.m is a sequence of m amino acids independently selected from the group consisting of: Glu, Ala, Leu, Met, Gln, Lys, Arg, Val, Ile, Trp, Phe and Asp, X.sub.i is a sequence of i amino acids each of which is any amino acid, n is 6 to 7, m is at least 1, and n, m, and i are selected to make the maximum length of said peptide 20 amino acids, and detecting binding between .alpha.v.beta.6 integrin and said peptide; and diagnosing the patient with a cancer that overexpresses .alpha.v.beta.6 when said binding between .alpha.v.beta.6 integrin and said peptide at the tumor is detected. 3. The method of claim 1, wherein said peptide is selected from the group consisting of A20FMDV2 (SEQ ID NO. 8) and DBD2 (SEQ ID NO: 16), said A20FMDV2 (SEQ ID NO: 8) and DBD2 (SEQ ID NO: 16) being optionally biotinylated. 4. The method of claim 1, wherein said peptide is A20LAP (SEQ ID NO: 6). 5. The method of claim 1, wherein said peptide is A20FMDV2 (SEQ ID NO: 8), said A20FMDV2 (SEQ ID NO: 8) being optionally biotinylated. 6. The method of claim 2, wherein said peptide is selected from the group consisting of A20FMDV2 (SEQ ID NO. 8) and DBD2 (SEQ ID NO: 16), said A20FMDV2 (SEQ ID NO: 8) and DBD2 (SEQ ID NO: 16) being optionally biotinylated. 7. The method of claim 2, wherein said peptide is A20LAP (SEQ ID NO: 6). 8. The method of claim 2, wherein said peptide is A20FMDV2 (SEQ ID NO: 8), said A20FMDV2 (SEQ ID NO: 8) being optionally biotinylated. 9. The method of claim 2, wherein said peptide is linked to a detectable moiety selected from the group consisting of: a radioactive moiety, a Magnetic Resonance Imaging (MRI) spin label, and an optical moiety, and wherein detecting binding between .alpha.v.beta.6 integrin and said peptide comprises detecting said detectable moiety. 10. The method of claim 2, wherein the method further comprises providing the patient with a cancer prognosis, wherein the patient is provided with a prognosis of reduced survival when the presence of .alpha.v.beta.6 integrin at the tumor is detected as compared with survival when the presence of .alpha.v.beta.6 integrin at the tumor has not been detected. 11. A method of imaging epithelial cells that overexpress .alpha.v.beta.6 integrin in the body of a patient, the method comprising: administering to the patient a peptide comprising the sequence motif B.sub.nRGDLX.sup.5X.sup.6LX.sup.8X.sup.9X.sup.10Z.sub.mX.sub.i or B.sub.nRGDLX.sup.5X.sup.6IX.sup.8X.sup.9X.sup.10Z.sub.mX.sub.i, wherein B.sub.n is a sequence of n amino acids each of which is any D- or L-amino acid, X.sup.5, X.sup.6, X.sup.8, X.sup.9, and X.sup.10 each independently represent any amino acid, Z.sub.m is a sequence of m amino acids independently selected from the group consisting of: Glu, Ala, Leu, Met, Gln, Lys, Arg, Val, Ile, Trp, Phe and Asp, X.sub.i is a sequence of i amino acids each of which is any amino acid, n is 6 to 7, m is at least 1, and n, m, and i are selected to make the maximum length of said peptide 20 amino acids, wherein said peptide is linked to a detectable moiety selected from the group consisting of: a radioactive moiety, a Magnetic Resonance Imaging (MRI) spin label, and an optical moiety; and detecting said detectable moiety to thereby image peptide epithelial cells that overexpress .alpha.v.beta.6 integrin. 12. The method of claim 11, wherein the patient is suffering from a condition selected from the group consisting of: chronic fibrosis, chronic obstructive pulmonary disease (COPD), lung emphysema, chronic wounding skin disease and an epithelial tumor. 13. A method of detecting .alpha.v.beta.6 integrin in a patient, said method comprising: a) obtaining a cell sample from a human patient; and b) detecting whether .alpha.v.beta.6 integrin is present in the cell sample by contacting the cell sample with a peptide comprising the sequence motif B.sub.nRGDLX.sup.5X.sup.6LX.sup.8X.sup.9X.sup.10Z.sub.mX.sub.i or B.sub.nRGDLX.sup.5X.sup.6IX.sup.8X.sup.9X.sup.10Z.sub.mX.sub.i wherein B.sub.n is a sequence of n amino acids each of which is any D- or L-amino acid, X.sup.5, X.sup.6, X.sup.8, X.sup.9, and X.sup.10 each independently represent any amino acid, Z.sub.m is a sequence of m amino acids independently selected from the group consisting of: Glu, Ala, Leu, Met, Gln, Lys, Arg, Val, Ile, Trp, Phe and Asp, X.sub.i is a sequence of i amino acids each of which is any amino acid, n is 6 to 7, m is at least 1, and n, m, and i are selected to make the maximum length of said peptide 20 amino acids, and detecting binding between .alpha.v.beta.6 integrin and said peptide. 14. The method of claim 13, wherein the cell is a cancer cell. 15. The method of claim 13, wherein said peptide is linked to a detectable moiety selected from the group consisting of: a radioactive moiety, a Magnetic Resonance Imaging (MRI) spin label, and an optical moiety, and wherein detecting binding between .alpha.v.beta.6 integrin and said peptide comprises detecting said detectable moiety.

Details for Patent 9,650,416

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Recordati Rare Diseases, Inc.	ELSPAR	asparaginase	For Injection	101063	01/10/1978		2025-10-03