Claims for Patent: 8,580,520

Summary for Patent: 8,580,520

Title:	YKL-40 as a marker for gastrointestinal cancers
Abstract:	The present invention relates to gastrointestinal cancers and methods for selecting a treatment for said gastrointestinal cancer in a subject. The present invention further relates to a methods of diagnosing the presence of and/or classifying the severity of a gastrointestinal cancer; together with methods for determining the effect of a therapy administered and/or the prognosis for a subject suffering from a gastrointestinal cancer, before, during or after administering the treatment. For all the methods applies that a determined level of YKL-40 above one or more reference levels indicates the treatment, the severity of the disease, the effect of the treatment and/or the prognosis of the subject. The reference level is typically a level obtained from healthy individuals or a level previously obtained from the same subject. The subject may suffer from any one or more gastrointestinal cancers, such as upper gastrointestinal cancers, and metastatic colorectal cancer. The present invention further relates to a kit and a device that may be used in the method of the present invention.
Inventor(s):	Johansen; Julia Sidenius (Frederiksberg, DK), Schultz; Nicolai Aagaard (Frederiksberg, DK), Jensen; Benny Vittrup (Roskilde, DK), Bojesen; Stig (Kobenhavn O, DK), Nordestgaard; Borge Gronne (Genrofte, DK), Nielsen; Hans Jorgen (Kongens Lyngby, DK), Christensen; Ib Jarle (Hillerod, DK)
Assignee:	Herlev Hospital (Herlev, DK) Rigshospitalet (Kobenhavn O, DK) Hvidovre Hospital (Hvidovre, DK)
Application Number:	13/063,402
Patent Claims:	1. A method for determining a therapy for a gastrointestinal cancer expressing wild type KRAS in a subject, said method comprising: i) determining the level of YKL-40 in a blood, serum, or plasma sample obtained from the subject; and ii) comparing said level of YKL-40 with a reference level of YKL-40 obtained in healthy individuals selected from the following set of age dependent cut-off values defined as the 90.sup.th percentile: natural log (ln)(plasma YKL-40 .mu.g/l)=3.5+0.02.times.age of the subject (years); the 95.sup.th percentile: ln(plasma YKL-40 .mu.g/l)=3.6+0.02.times.age of the subject (years); and the 97.5.sup.th percentile: ln(plasma YKL-40 .mu.g/l)=3.9+0.02.times.age of the subject (years); and iii) treating said subject with an EGFR inhibitor when the determined level of YKL-40 is below the reference level. 2. The method of claim 1, further comprising the following steps: iv) determining the level of YKL-40 in a sample obtained from said subject after a period of treatment; and v) comparing said YKL-40 level with the YKL-40 level obtained in step i), wherein the level of YKL-40 in the sample of step i) is age adjusted by adding 0.5 .mu.g/l per year for women, and 0.8 .mu.g/l per year for men, and wherein said treatment is continued if the level of YKL-40 in the sample of step iv) is below or equal to the age adjusted level obtained in step i). 3. The method according to claim 2, wherein a level of YKL-40 in the sample being increased to at least a factor of 1.60 or more compared to the level obtained in step i) indicates that the gastrointestinal cancer has evolved to a more severe stage of the cancer, therefore suggesting a therapy with higher efficacy than the treatment of step iii), or wherein a level of YKL-40 in the sample being decreased to at least a factor of 0.6 compared to the level obtained in step i) indicates that the gastrointestinal cancer has evolved to a less severe stage of the cancer, therefore suggesting a continuation of said treatment of step iii) or initiation of a therapy with lower efficacy than the treatment of step iii). 4. The method according to claim 2, wherein a level of YKL-40 in the sample being increased by at least 109% compared to the level obtained in step i) indicates that the gastrointestinal cancer has evolved to a more severe stage of the gastrointestinal cancer, therefore suggesting a therapy with higher efficacy than the treatment of step iii), or wherein a level of YKL-40 in the sample being decreased by 52% compared to the level obtained in step i) indicates that the gastrointestinal cancer has evolved to a less severe stage of the gastrointestinal cancer, therefore suggesting a continuation of said treatment of step iii) or initiation of a therapy with lower efficacy than the treatment of step iii). 5. The method according to claim 1, wherein the gastrointestinal cancer is an upper GI cancer and/or a lower GI cancer. 6. The method according to claim 1, wherein the gastrointestinal cancer is an upper GI cancer. 7. The method according to claim 1, wherein the gastrointestinal cancer is one or more upper GI cancers selected from the group consisting of esophageal cancer, gastric/stomach cancer, pancreatic cancer and biliary cancer. 8. The method according to claim 1, wherein the gastrointestinal cancer is pancreatic cancer. 9. The method according to claim 1, wherein the gastrointestinal cancer is one or more lower GI cancers selected from the group consisting of small intestine cancer, duodenum cancer, appendix cancer, colon cancer, rectal cancer, colorectal cancer and anal cancer. 10. The method according to claim 1, wherein the gastrointestinal cancer is colorectal cancer or metastatic colorectal cancer. 11. The method according to claim 1, wherein the gastrointestinal cancer is metastatic colorectal cancer. 12. The method according to claim 1, wherein the EGFR inhibitor is selected from the group consisting of Cetuximab, Panitumumab, Zalutumumab, and Erlotinib. 13. The method according to claim 1, further comprising determining wherein the level of one or more additional biomarkers in the same sample as the YKL-40 level. 14. The method according to claim 13, wherein the one or more additional biomarkers is selected from the group consisting of BRAF mutation status, PTEN expression, microsatelite instability (MSI), AREG expression, EREG expression, CRP, ESR, CEA, CA19-9, LDH, tissue inhibitor of metalloproteinase 1 (TIMP1), interleukins, IL-4, IL-6, IL-8, VEGF, metalloproteinases, soluble UPAR (sUPAR), tumor necrosis factor-alpha, the aminoterminal propeptide of type I and III procollagen (P-III-NP), monocyte chemoattractant protein-1, fibrin D-dimer and other gene-, microRNA and SNP biomarkers identified from array studies.

Details for Patent 8,580,520

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	02/12/2004		2028-09-15
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	03/28/2007		2028-09-15
Amgen, Inc.	VECTIBIX	panitumumab	Injection	125147	09/27/2006		2028-09-15