Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Status of the Claims
Claims 1-19 are pending and are examined on their merits.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The Information Disclosure Statement filed on September 11th 2023 is in compliance with the provisions of 37 CFR 1.97 and has been considered in full. A signed copy of references cited from the IDS is included with this Office Action.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-3 and 8-9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Dong (Dong et al., (2005). Downregulation of XIAP and induction of apoptosis by the synthetic cyclin-dependent kinase inhibitor GW8510 in non-small cell lung cancer cells. Cancer Biology & Therapy, 5(2), 165–170).
Claims 1-2 are directed towards the treatment of cancer via administration of GW8510, a CDK inhibitor. Dong teaches the treatment of cancer via administration of GW8510 (Dong, Abstract):
“In order to evaluate the antitumor activity of one such inhibitor, GW8510, against human lung cancers, we analyzed the effects of GW8510 on six nonsmall cell lung cancer (NSCLC) cell lines (A549, H1299, H460, H226, H358 and H322) and normal human fibroblast (NHFB).”
“These results suggest that GW8510 might provide a treatment strategy for human NSCLC and XIAP is an important target for GW8510-induced apoptosis of NSCLC cells that occurs through inhibition of XIAP mRNA transcription.”
Dong therefore anticipates claims 1-2.
Claim 3 limits the cancer of claim 1 to solid cancer. Dong teaches the treatment of nonsmall cell lung cancer (Dong, Abstract), anticipating claim 3.
Claim 8 requires that the cancer of claim 1 has KRAS mutation and is anticipated by Dong, who teaches the treatment of the H358 cancer cell line1, which is known to carry the KRAS G12C mutation.
Claim 9 limits the mutation in claim 8 to KRAS G12C and is anticipated for the same reasons.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-9 are rejected under 35 U.S.C. 103 as being unpatentable over Dong in view of Pao (Pao et al., KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med. 2005 Jan;2(1):e17).
For the teachings of Dong as they relate to claims 1-3 and 8-9, see the above 102 rejection for claims 8 and 9.
Claims 4-7 limit the cancer of claim 1 to cancers resistant to EGFR tyrosine kinase inhibitors, such as erlotinib. For the teachings of Dong as they are relevant to claim 1 and the treatment of KRAS G12C mutated cancers, see the above 102 rejections for claims 1 and 8. One of ordinary skill in the art would have a reasonable expectation of success in treating erlotinib-resistant cancers with GW8510, because KRAS G12C cancers, such as those treated by Dong, are known in the art to typically have erlotinib resistance. For example, see Pao, who teaches that KRAS-mutated cancers (Pao, pg. 0058, Table 1), including those with the G12C mutation (Pao, pg. 0060) typically have very low response to erlotinib (i.e. are erlotinib-resistant). Claims 4-7 are therefore prima facie obvious.
Claims are rejected under 35 U.S.C. 103 as being unpatentable over Dong in view of Pao and in further view of Guevara (Guevara et al., Intrinsic caspase-8 activation mediates sensitization of erlotinib-resistant tumor cells to erlotinib/cell-cycle inhibitors combination treatment. Cell Death Dis. 2012 Oct 25;3(10):e415).
Claim 10 is directed towards an adjuvant comprising GW8510, a known CDK inhibitor. Claims 11-15 limit the additional agent in the adjuvant to an EGFR tyrosine kinase inhibitor, such as erlotinib. For the teachings of Dong as they are relevant to the treatment of KRAS cancers with GW8510, see the above 102 rejections for claim 1.
Regarding the combination treatment of GW8510 and erlotinib, one of ordinary skill in the art would have a reasonable expectation of success in treating cancers with an adjuvant comprising GW8510 and erlotinib, because similar CDK inhibitors are known in the art to re-sensitize erlotinib-resistant cancer cells to the drug. For example, see Guevara, who uses NBI1, a CDK inhibitor, to resensitize erlotinib-resistant cells to the drug, and proposes a combination treatment of erlotinib and NBI1 as an anti-cancer combination treatment in erlotinib-resistant cells:
“Here, we show that NBI1 sensitizes erlotinib-resistant tumor cells to the combination treatment for apoptosis-mediated cell death. Importantly, in both erlotinib-sensitive and erlotinib resistant cells, the effective dose of erlotinib was lower in the presence of TAT-NBI1. Among the key hallmarks of this process are the accumulation of damaged DNA in the cells and the depletion of cellular levels of inhibitor of apoptosis proteins (IAP) that induced the activation of caspase-8 and caspase-10. These two caspases were necessary for full apoptosis activation. siRNA-based silencing revealed that further activation of caspase-2 was caspase-10-dependent. Lastly, we provide novel evidence that TAT-NBI1/erlotinib co-treatment of erlotinib-resistant cells activates a death domain kinase RIP1-dependent apoptotic pathway that induces cell death.”
[Guevara, pg. 2]
“These results suggested that a coadministration of a CDK2/cyclin A inhibitor with erlotinib resensitizes resistant cells to erlotinib, and it also reduces the lethal dose in erlotinib-sensitive cells, thereby widening the therapeutic window of the drug while diminishing the possible side effects.”
[Guevara, pg. 2]
One of ordinary skill in the art would therefore have a reasonable expectation of success in using a CDK inhibitor, such as GW8510, in combination with erlotinib in the treatment of cancer, and claims 10-15 are thereby prima facie obvious.
Claim 16 requires that the anticancer adjuvant of claim 10 inhibits resistance to the anticancer agent. As Guevara teaches the resensitization of cancer cells to erlotinib after the administration of CDK inhibitors, claim 16 is prima facie obvious for the same reasons as claim 10.
Claims 17-19 are rejected under 35 U.S.C. 103 as being unpatentable over Dong in view of Pao and in further view of Chen (Chen et al., Gemcitabine resistance mediated by ribonucleotide reductase M2 in lung squamous cell carcinoma is reversed by GW8510 through autophagy induction. Clin Sci (Lond) 18 July 2018; 132 (13): 1417–1433).
Claim 17 is directed to the treatment of cancer comprising administration of GW8510 in a food composition. For the teachings of Dong as they are relevant to the treatment of cancers with GW8510, see the above 102 rejection for claim 1. Regarding the food composition, Chen teaches oral administration of GW8510 (Chen, pg. 1428), and claim 17 is therefore prima facie obvious.
Claim 18 limits the cancer of claim 17 to EGFR inhibitor-resistant cancer. For the teachings of Pao as they relate to the treatment of EGFR inhibitor-resistant cancer with GW8510, see the above 103 rejection of claims 4-7. Claim 18 is thereby prima facie obvious for the same reasons as claim 17.
Claim 19 limits the cancer of claim 17 to cancer with KRAS mutation. For the teachings of Dong as they relate to the treatment of KRAS mutated cancers with GW8510, see the above 102 rejection of claim 8. Claim 19 is thereby prima facie obvious for the same reasons as claim 17.
Conclusion
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/A.J.S./Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
1 For evidentiary support on the presence of the KRAS G12C mutation in the H358 cell line, see cancer.gov (cancer.gov/cell-lines updated July 10th 2018)