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
Claims 5-20, 22-23, 26-27 and 32 are pending in the present application.
AMENDMENTS
The amendments filed 09/17/2025 have been entered in the present application file.
Previous Claim Rejections - 35 USC § 101
Claims 26-27 were previously rejected under 35 U.S.C. 101 because the claimed invention was directed to non-statutory subject matter.
Applicant has amended the claims to direct the reference claims to statutory subject matter.
The previous rejection is withdrawn.
Previous Claim Rejections - 35 USC § 112
Claims 11-12 and 26-27 were previously 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.
Applicant has amended the claims to remove the indefinite subject matter and indefinite phrasing.
The rejections are withdrawn.
Previous Claim Rejections - 35 USC § 103
Claims 5-20, 22-23, 26-27 and 32 were previously rejected under 35 U.S.C. 103 as being unpatentable over WO 2018/203219 A1 (Cooke), in view of WO 2017/205756 A1 (Shay; published 11/30/2017).
Applicant has amended the claims to require wherein the melanoma is unresectable cutaneous melanoma and traverses the previous rejection on grounds Cooke does not disclose the combination of naporafenib and trametinib for the treatment of unresectable cutaneous melanoma. Applicant further argues Shay does not teach or suggest the use of naporafenib or trametinib to treat unresectable cutaneous melanoma, and discloses a method of treatment unrelated to RAF.
The Examiner has considered the amendment and traversal fully but must disagree for the following reasons.
Cooke discloses trametinib has been approved for the treatment of unresectable or metastatic malignant melanoma with B-Raf V600E or V600K mutations. See page 13, lines 9-20. Cooke discloses working examples demonstrating the effects of the combination of naporafenib and trametinib in treating various melanoma cell lines including cell lines derived from cutaneous melanoma subjects. See Example 1B and Example 2 on pages 39-40 and 44-46, respectively of Cooke.
Shay discloses a method of treating a subject with melanoma comprising administering to said subject a therapeutically effective amount of 6-thio-2'-deoxyguanosine (6-thio-dG), wherein melanoma is resistant to an immunotherapy and/or MAPKi therapy. See claims 2 and 5-7 of Shay. Shay discloses where the melanoma resistant/refractory to immunotherapy to be treated is BRAF V600 mutant melanoma. See pages 88-90 and claims 6-8 of Shay. Shay discloses working examples where the melanoma to be treated is human skin cutaneous melanoma. See Example 2 on pages 27-28 and Table 7 on page 95.
“It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
As Cooke and Shay both teach a composition suitable for the treatment of BRAFV600-mutant melanoma, wherein the melanoma is cutaneous melanoma, including unresectable or malignant melanoma, it would have been prima facie obvious to one of ordinary to skill to combine these compositions to form a third composition suitable for the same utility, the treatment of cutaneous melanoma, where the cutaneous melanoma is unresectable. There would be a reasonable expectation of success for one of ordinary skill in the art based on the efficacy and utility disclosed in the prior art disclosures, particularly from Cooke which discloses the combination of naporafenib and trametinib for the same purpose and Shay which discloses the treatment of similarly mutant melanoma which is resistant/refractory to previous treatment and/or unresectable.
Therefore, the rejection of 06/18/2025 is maintained in an amended form due to Applicant’s amendments.
Previous Double Patenting Rejection
Claims 5-20, 22-23, 26-27 and 32 were previously provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-3, 9-10, 13 and 27-30 of copending Application No. 19/024,258 in view of WO 2018/203219 A1 (Cooke) and WO 2017205756 A1 (Shay; published 11/30/2017).
Claim 5-7 were previously provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-5 of copending Application No. 18/679,016 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because they are both drawn to a method of treating cancer comprising a combination of naporafenib and trametinib.
Applicant notes that Application Nos. 19/024,258 and 18/679,016 have been abandoned. The Examiner has acknowledged the abandoned applications and the previous provisional non-statutory double patenting rejections over the ‘258 application and ‘016 application have been withdrawn.
Information Disclosure Statement
The Information Disclosure Statement(s) filed 09/16/2025 and 10/03/2025 have been acknowledged and considered by the Examiner.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 5-20, 22-23, 26-27 and 32 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2018/203219 A1 (Cooke), in view of WO 2017205756 A1 (Shay; published 11/30/2017).
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Cooke discloses a pharmaceutical combination of naporafenib (compound of formula (I) in Cooke) and a MEK inhibitor, comprising trametinib, for use in treatment of BRAF V600-mutant melanoma or NRAS mutant melanoma. See claims 1, 3, 20-21, and 27 of Cooke. Cooke discloses as a monotherapy trametinib has been approved for the treatment of unresectable or metastatic malignant melanoma with B-Raf V600E or V600K mutations. See page 13, lines 9-20. See present claims 5-6 and 8-10. Cooke discloses working examples demonstrating the effects of the combination of naporafenib and trametinib in treating various melanoma cell lines including cell lines derived from cutaneous melanoma subjects. See Example 1B and Example 2 on pages 39-40 and 44-46, respectively of Cooke.
Cooke provides where NRAS-mutant melanoma of the disclosure includes melanoma having at least one NRAS mutation corresponding to Q61K, Q61L or Q61R. See page 28, lines 8-9. See present claim 7.
Cooke teaches where the combination is suitable for the treatment of melanoma, where melanoma is refractory to chemotherapy, in particular to refractory to treatment with a combination of BRAF inhibitors, such as dabrafenib, and MEK inhibitors, such as trametinib. See pages 27-28 as well as present claims 11-12 and 14-17.
Cooke discloses wherein the total daily dose of naporafenib or trametinib is administered once daily as well as continuously or intermittently. See page 31, lines 18-23 and page 32, lines 6-7. See present claims 18-20. Cooke discloses where naporafenib can be administered at a unit dosage of about 50 mg – 800 mg, and where trametinib can be administered in a dosage from 0.125 mg/day to 10 mg/day, preferably 0.5, 1 or 2 mg/day trametinib. See page 32, lines 14-26 and page 33, lines 8-19. See also present claims 22-23 and 26-27.
Cooke provides a dose of about 200 mg of naporafenib may be administered twice per day and (total daily dose about 400 mg) and a dose of about 1.0 mg or about 2.0 mg of trametinib may be administered once per day. See page 33, lines 13-16. See present claim 32.
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
Cooke does not disclose or suggest wherein the melanoma to be treated is resistant or refractory to treatment with immunotherapy.
Finding of prima facie obviousness --- rationale and motivation (See
MPEP § 2142-2143)
Shay discloses a method of treating a subject with melanoma comprising administering to said subject a therapeutically effective amount of 6-thio-2'-deoxyguanosine (6-thio-dG), wherein melanoma is resistant to an immunotherapy and/or MAPKi therapy. See claims 2 and 5-7. Shay discloses where the melanoma to be treated is BRAF V600 mutant melanoma. See pages 88-90. Shay discloses working examples where the melanoma to be treated is human skin cutaneous melanoma. See Example 2 on pages 27-28 and Table 7 on page 95.
Shay provides wherein the method may further comprise treating said subject with a second cancer therapy, such as an immunotherapy, such as ipilumumab and nivolumab or combination of ipilumumab and nivolumab, a radiotherapy, a neoadjuvant chemotherapy (such as plantinum/taxane), a toxin therapy, a hormonal therapy or surgery. See page 2, lines 26-30 and pages 18-21.
“It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
As Cooke and Shay both teach a composition suitable for the treatment of BRAFV600-mutant melanoma, wherein the melanoma is cutaneous melanoma, including unresectable or malignant melanoma, it would have been prima facie obvious to one of ordinary to skill to combine these compositions to form a third composition suitable for the same utility, the treatment of cutaneous melanoma, where the cutaneous melanoma is unresectable. There would be a reasonable expectation of success for one of ordinary skill in the art based on the efficacy and utility disclosed in the prior art disclosures, particularly from Cooke which discloses the combination of naporafenib and trametinib for the same purpose and Shay which discloses the treatment of similarly mutant melanoma which is resistant/refractory to previous treatment and/or unresectable.
Conclusion
Claims 5-20, 22-23, 26-27 and 32 are rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to QUINCY A MCKOY whose telephone number is (703)756-4598. The examiner can normally be reached Monday - Thursday 8:00 - 6:00.
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/QUINCY A. MCKOY/
Patent Examiner, Art Unit 1626
/KAMAL A SAEED/Primary Examiner, Art Unit 1626
/JOSEPH K MCKANE/Supervisory Patent Examiner, Art Unit 1626