DETAILED ACTION
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 .
Status of the Application
Claims 1-3, 7, 9-10, 12-13, 15, 22-23, 27, 29-30, 33, 35-36, 58, 60, 62 are pending and are examined herein.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
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Claims 1-3, 7, 9-10, 12-13, 15, 22-23, 27, 29-30, 33, 35-36, 58, 60, 62 are provisionally rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 19-23, 25-30, 32-36, 38 of copending Application No. 17/999,799 in view of Bjerkvig et al. (WO 2019/207087, of record), Park et al. (WO 2019/107971, of record), and Decrescenzo et al. (WO 2018/213302, of record).
The referenced claims recite a method of treating melanoma having a NRASQ61L mutation by administering belvarafenib at 200-1300 mg per day. However, the referenced claims fail to disclose metastasis into the brain, the claimed dosage, and cobimetinib. The fact pattern for this obviousness rejection is the same as the 103 rejection below. This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Claims 1-3, 7, 9-10, 12-13, 15, 22-23, 27, 29-30, 33, 35-36, 58, 60, 62 are provisionally rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1-13 of copending Application No. 18/516,552 in view of Bjerkvig et al. (WO 2019/207087, of record), Park et al. (WO 2019/107971, of record), and Decrescenzo et al. (WO 2018/213302, of record).
The referenced claims recite a method of treating melanoma having a NRAS mutation by administering HM95573 (belvarafenib) and cobimetinib. However, the referenced claims fail to disclose metastasis into the brain and the claimed dosage. The fact pattern for this obviousness rejection is the same as the 103 rejection below. This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Claims 1-3, 7, 9-10, 12-13, 15, 22-23, 27, 29-30, 33, 35-36, 58, 60, 62 are provisionally rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 46-65 of copending Application No. 18/554,041 in view of Bjerkvig et al. (WO 2019/207087, of record).
The referenced claims recite a method of treating melanoma having a NRASQ61L mutation by administering belvarafenib and cobimetinib. However, the referenced claims fail to disclose metastasis into the brain. The fact pattern for this obviousness rejection is the same as the 103 rejection below. This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Claims 1-3, 7, 9-10, 12-13, 15, 22-23, 27, 29-30, 33, 35-36, 58, 60, 62 are provisionally rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1-2, 4, 6, 10-12, 15, 23, 25-26, 36 of copending Application No. 18/554, 236 in view of Bjerkvig et al. (WO 2019/207087, of record), Park et al. (WO 2019/107971, of record), and Decrescenzo et al. (WO 2018/213302, of record).
The referenced claims recite a method of treating melanoma having a BRAFV600E mutation by administering belvarafenib at 250-500 mg per day. However, the referenced claims fail to disclose metastasis into the brain and cobimetinib. The fact pattern for this obviousness rejection is the same as the 103 rejection below. This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Claims 1-3, 7, 9-10, 12-13, 15, 22-23, 27, 29-30, 33, 35-36, 58, 60, 62 are rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 11,859,252 in view of Bjerkvig et al. (WO 2019/207087, of record), Park et al. (WO 2019/107971, of record), and Decrescenzo et al. (WO 2018/213302, of record).
Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims recite a method of treating melanoma having a KRAS mutation by administering HM95573 (belvarafenib) and cobimetinib. However, the referenced claims fail to disclose metastasis into the brain, specific mutations, and the claimed dosage. The fact pattern for this obviousness rejection is the same as the 103 rejection below.
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 1-3, 7, 9-10, 12-13, 15, 22-23, 27, 29-30, 33, 35-36, 58, 60, 62 are rejected under 35 U.S.C. 103 as being unpatentable over Bae et al. (“Abstract 2606: Antitumor activity of the selective RAF inhibitor HM95573 in melanoma,” Experimental and Molecular Therapeutics, 2015, 1-4, of record) in view of Bjerkvig et al. (WO 2019/207087, of record), Park et al. (WO 2019/107971, of record), and Decrescenzo et al. (WO 2018/213302, of record).
The instant claims are directed to a method of treating a metastatic melanoma metastasis in the brain or a method of treating brain cancer metastasized from melanoma by administering a belvarafenib and the MEK inhibitor, cobimetinib, wherein the cancer carries a BRAFV600E mutation.
Bae et al. teach that the mitogen-activated protein kinase (MAPK) pathway is particularly important for the survival and proliferation of tumor cells. Activation of the MAPK pathway due to mutations in BRAF and NRAS is considered one of the causes of melanoma. HM95573 (also known as belvarafenib) is a novel, highly potent RAF kinase inhibitor, which shows high selectivity toward BRAF mutant kinases, for example BRAFV600E. Belvarafenib potently inhibited the growth of mutant BRAF melanoma cell lines and showed excellent antitumor activity in mouse models with both BRAF and NRAS mutation cell lines.
However, Bae et al. fail to disclose metastasis into the brain, the claimed dosage, and cobimetinib.
Bjerkvig et al. teach methods of treating metastatic cancer by administering a pharmaceutical composition comprising beta-sitosterol in combination with MEK inhibitor (abstract), for example cobimetinib (page 7, lines 15-17). In a preferred embodiment, the cancer is a metastatic melanoma with metastases in the brain (page 4, lines 13-14). Amounts effective will depend, of course, on the particular subject being treated; the severity of a condition, disease or disorder; the individual patient parameters including age, physical condition, size and weight; the duration of the treatment; the nature of concurrent therapy (if any); the specific route of administration and like factors within the knowledge and expertise of the health practitioner. These factors are well known to those of ordinary skill in the art and can be addressed with no more than routine experimentation. It is generally preferred that a maximum dose be used, that is, the highest safe dose according to sound medical judgment. It will be understood by those of ordinary skill in the art, however, that a patient may insist upon a lower dose or tolerable dose for medical reasons, psychological reasons or for virtually any other reason (page 22, lines 11-26).
Park et al. teach a method of treating abnormal cell growth, for example melanoma or brain cancer, by administering a compound of formula I (also known as belvarafenib) (paragraphs 124-125). The administration dose may vary depending on the subject to be treated, severity of the illness, or health of the subject, administration rate, and physician’s decision, but it may be conventionally administered to a human subject, for instance, 70 kg, in an amount of from 10 mg to 2,000 mg, preferably 50 mg to 1,000 mg, 1 to 4 times daily. In some cases, it may be more appropriate to administer a lower or higher dosage than that mentioned above (paragraph 127).
Decrescenzo et al. teach methods of treating cancers with a BRAF mutation (abstract), for example melanoma or gliobastoma (paragraph 0019), by administering a MEK inhibitor (paragraph 0021), for example cobimetinib (paragraph 0022 and claim 16). A suitable dosage for all anti-cancer agents is 1 mg/kg per day (paragraph 0211).
It is noted that the claimed dosage of 2.5 to 25 mg/kg for the same 70 kg subject in Park et al. equates to 175 to 1,750 mg, which is encompassed by the teachings of the reference. Similarly, the claimed dosage of 20-100 mg of the MEK inhibitor is taught by in Decrescenzo et al. since for a 70 kg subject, the amount of MEK inhibitor would equate to 70 mg. It is also obvious to administer the active agents for 28 consecutive days or as long as the symptoms persist or the cancer is still diagnosed. The limitations regarding brain cancer metastases or brain cancer cells are obvious to occur since all elemental steps of the claims have been taught by the cited prior art.
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art, prior to the effective filing date of the claimed invention, to have treated a metastatic melanoma with metastases in the brain by combining a pharmaceutical composition comprising beta-sitosterol and the MEK inhibitor, cobimetinib, as taught by Bjerkvig et al., with belvarafenib, as taught by Bae et al., in the claimed dosage amounts, as taught by Park and Decrescenzo et al.
A person of ordinary skill in the art would have been motivated to treat metastatic melanoma with metastases in the brain because not only does both Bjerkvig and Bae et al. teach treating melanoma, but Bjerkvig et al. teaches that metastatic melanoma with metastases in the brain is known in the art. Since metastatic melanoma with metastases in the brain is a specific species to the broad genus of melanoma, it is obvious absent a teaching of unexpected results.
A person of ordinary skill in the art would have been motivated to combine the MEK inhibitor, cobimetinib, with belvarafenib because both have been individually known to be useful in treating melanoma. Therefore, one of ordinary skill in the art would have had a reasonable expectation of success in treating melanoma with the therapeutically additive effect of both belvarafenib and cobimetinib.
A person of ordinary skill in the art would have been motivated to administer belvarafenib and cobimetinib at the claimed dosages because the cited prior art teaches that these dosage ranges are recommended for use in treating melanoma. Therefore, one of ordinary skill in the art would have had a reasonable expectation of success in melanoma by administering belvarafenib and cobimetinib at the claimed dosages.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Yong S. Chong whose telephone number is (571)-272-8513. The examiner can normally be reached Monday to Friday: 9 AM to 5 PM EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam Milligan, can be reached at (571)-270-7674. The fax phone number for the organization where this application or proceeding is assigned is (571)-273-8300.
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/Yong S. Chong/Primary Examiner, Art Unit 1623