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 .
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 3-12, 17-18, 22-23, 39-40, 44-45 and 62 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 1, the phrase "effective amount of Compound A" renders the claim indefinite because it is unclear what the structural limitations is for compound A. The claim fails to identify the structure or chemical name of Compound A. Ultimately the metes and bounds of the claim is unclear.
Claims 3-12, 17-18, 22-23, 39-40, 44-45 and 62 are additionally rendered indefinite as depending from claim 1 without further limiting Compound A.
For the purposes of prior art, examiner is interpreting Compound A as (R)-N-(2-(5-fluoropyridin-3-yl)-8- isopropylpyrazolo[1,5-a][1,3,5]triazin-4-yl)-2,3,4,9-tetrahydro-1H-carbazol-3-amine from the specification.
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, 3-12, 17-18, 22-23, 39-40, 44-45 and 62 are rejected under 35 U.S.C. 103 as being unpatentable over Castro et al. (WO 2018195397 A2) in view of Kelly (WO 2018227244 A1).
Regarding claims 1, 3-12, 17-18, 22-23, 39-40, 44-45 and 62, Castro teaches methods for the treatment of cancers of melanoma, liposarcoma, lung, breast, prostate, leukemia, kidney, esophageal, brain, lymphoma or colon (relevant to claims 44-45) (para. 00121) comprising compounds useful as inhibitors of AHR in combination with another anti-cancer, cytotoxin, or chemotherapeutic agent (para. 00147). Of the AHR inhibitors Castro teaches structure I-40
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(R)-N-(2-(5-fluoropyridin-3-yl)-8- isopropylpyrazolo[1,5-a][1,3,5]triazin-4-yl)-2,3,4,9-tetrahydro-1H-carbazol-3-amine and a list of anti-cancer’s comprising doxorubicin (relevant to claim 62) (para. 00147). Castro teaches in some embodiments the AHR inhibitor is combined with an immuno-oncology PD-1 antagonist consisting of nivolumab and pembrolizumab (relevant to claims 1, 12, 17-18) (para. 00160).
Castro additionally teaches the AHR inhibitors are formulated a dosage of between 0.01 - 100 mg/kg body weight/day one or more times a day, to obtain the desired therapeutic effect (relevant to claims 3-11) (para. 0093, 00100).
Castro fails to teach the PD-1 antagonist at the claimed mg amount once about every 1, 2, 3 or 4 weeks.
Kelly teaches Nivolumab a human IgG4 anti-PD-1 mAb, should be administered at 3 mg/kg every 2 weeks to treat melanoma, metastatic melanoma, metastatic squamous NSCLC, renal cell carcinoma, and bladder cancer. Kelly additionally teaches pembrolizumab administered at 2 mg/kg or 10 mg/kg every 2 weeks or 3 weeks, for the same cancers as above (relevant to claims 22-23) (Page 7, 3rd and 5th para.)
Therefore, it would have been obvious to someone of ordinary skill in the art at the time of filling to have administered (R)-N-(2-(5-fluoropyridin-3-yl)-8- isopropylpyrazolo[1,5-a][1,3,5]triazin-4-yl)-2,3,4,9-tetrahydro-1H-carbazol-3-amine in the claimed dosage amount and anti-PD-1 antibody of nivolumab or pembrolizumab in the claimed amount every 2 or 3 weeks to treat cancer. One would have been motivated to do so from the teachings of Castro of the administration of (R)-N-(2-(5-fluoropyridin-3-yl)-8- isopropylpyrazolo[1,5-a][1,3,5]triazin-4-yl)-2,3,4,9-tetrahydro-1H-carbazol-3-amine and an anti-PD-1 antibody to treat cancer, wherein the R)-N-(2-(5-fluoropyridin-3-yl)-8- isopropylpyrazolo[1,5-a][1,3,5]triazin-4-yl)-2,3,4,9-tetrahydro-1H-carbazol-3-amine is a dosage of .01 to 100 mg/k weight falls within the claimed range of child to adult patients. Additionally the teachings of Kelly on nivolumab and pembrolizumab used to treat cancer by administration of 2 mg/kg , 3mg/kg or 10 mg/kg weight falls within the claimed range of child to adult patients.
It would also have been obvious to administer the antibody at about 4 weeks (relevant to claims 39-40) as Kelly teaches the 2 or 3 weeks as example treatments and it would have been routine experimentation to treat the patient close to 4 weeks as per MPEP 2144.05 (II): [W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Conclusion
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MIKHAIL O'DONNEL. ROBINSON
Examiner
Art Unit 1627
/MIKHAIL O'DONNEL ROBINSON/Examiner, Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627