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
The preliminary amendment dated 7 December 2023, in which claims 1, 3-17 have been amended, claims 2, 18-21 have been cancelled, and new claim 22 has been added, is acknowledged.
Claims 1, 3-17, 22 are pending in the instant application.
Claims 1, 3-17, 22 are being examined herewith.
Priority
The instant application is a 35 U.S.C. § 371 U.S. national entry of International Application PCT/GB2022/051442, filed on 9 June 2022, which claims the benefit of Great Britain Patent Application No. 2108224.3, filed on 9 June 2021.
A certified copy of the priority document has been submitted on 7 December 2023.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 7 December 2023, 21 February 2024, 3 May 2024, 15 May 2024 and 24 December 2024 are acknowledged and considered.
Claim Rejections- 35 USC 103
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 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 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, 4-17, 22 are rejected under 35 U.S.C. 103 as being unpatentable over
Liu et al. (WO 2010/042163, cited in IDS), in view of Markham et al. (Drugs 2020, 80, 931-937, cited in PTO-892).
Liu (WO 2010/042163) teaches that nitroxoline is an inhibitor of angiogenesis (Figures 8, 9) and is a selective inhibitor of MetAP2 (Figure 2) and SIRT1 (Figure 5) , effective to treat diseases associated thereof, such as, for example, neurofibroma (page 35, line 13; page 37, line 6) or neurofibromatosis (page 27, line 6, line 11; page 35, line 5, line 13; page 36, line 29; page 38, line 12).
Liu teaches that nitroxoline is administered to a subject orally, or parenterally, or intravenously (page 34, lines 3-5), as in instant claims 12, 13.
The subject is a human (page 34, lines 10-11), as in instant claim 4.
The compound is administered in a dosage of 0.1 to 120 mg/kg/day, which, for a person of 60 kg, corresponds to 6 mg to 7.2 g/day, which encompasses the amounts in instant claims 5, 7, 9, 11.
Liu teaches administering the compound in a dosage of less than 500 mg/day (page 34, line 9), which overlaps with the amounts/dose in instant claims 5, 7, 9, 11.
Liu teaches that the compound is administered once, or twice daily (page 58, lines 8-9, as in instant claim 6; the dosing interval can be adjusted according to the needs of individual patients (page 58, lines 13-14).
Liu teaches a composition comprising nitroxoline as the only active agent in the composition, as in instant claim 14.
Liu does not teach treating cutaneous neurofibroma as the subtype of neurofibroma to be treated, as in instant claims.
Liu does not teach that nitroxoline is administered three times a day, or four times a day, as in instant claims 8-11.
Liu does not teach co-administration of 1-75 mg of selumetinib in the method of treating neurofibroma, as in instant claims 15-17, 22.
Markham et al. (Drugs 2020, 80, 931-937, cited in PTO-892) teach selumetinib is effective to treat neurofibromatosis (page 931, left column, first paragraph). Markham teaches (page 933, left column, second paragraph) orally administering of 50 mg of selumetinib, or orally administering 75 mg selumetinib, amounts which are within the range in instant claims 17, 22.
Markham teaches (Table page 936) a method of treating patients with neurofibromatosis type 1 and cutaneous neurofibroma by administering selumetinib (NCT02839720, 5th line in the Table).
Marham does not teach a method of treating cutaneous neurofibroma with a combination of nitroxoline and selumetinib, as in instant claims 15-17, 22.
It would have been obvious for a person of ordinary skill in the art to use the teachings of Liu to arrive at the instant invention. The person of ordinary skill in the art would have been motivated to administer nitroxoline to treat cutaneous neurofibroma, because Liu teaches that nitroxoline effective to treat, for example, neurofibroma. Thus, the person of ordinary skill in the art would have administered nitroxoline to a subject suffering from neurofibroma, or a subtype of neurofibroma which is cutaneous neurofibroma, with a reasonable expectation of achieving therapeutic effect.
Further, regarding claims 8-11, the person of ordinary skill in the art would have used the amount/dose taught by Liu, and would have explored different dosing intervals, such as 3 times a day, or 4 times a day, because Liu teaches that the dosing interval can be adjusted according to the needs of individual patients. Determining the dosing interval/frequency of administration, with the aim of optimizing therapeutic effect, is routine, well within the skill of the artisan.
Regarding claims 15-17, 22, he person of ordinary skill in the art would have been motivated to add selumetinib to nitroxoline, and administer the resulting combination in a method of treating cutaneous neurofibroma. One of ordinary skill in the art would have reasonably expected that adding selumetinib to a composition comprising nitroxoline, known or expected to be useful for the same purpose, will result in a composition/combination effective to treat neurofibroma or a subtype of neurofibroma which is cutaneous neurofibroma. Since active ingredients are known or expected to be effective against neurofibroma/neurofibromatosis, it is considered prima facie obvious to combine them into a single composition useful for the same purpose. At least additive effects would have been reasonably expected. See In re Kerkhoven, 205 USPQ 1069 (CCPA 1980).
As such, claims 1, 4-17, 22 are rejected as prima facie obvious.
Claims 1, 3 are rejected under 35 U.S.C. 103 as being unpatentable over
Liu et al. (WO 2010/042163, cited in IDS), in view of Dasgupta et al. (Cancer Res. 2005, 65 (21), 9843-9850, cited in PTO-892).
Liu (WO 2010/042163) teaches that nitroxoline is a selective inhibitor of MetAP2 (Figure 2), effective to treat diseases associated thereof, such as, for example, neurofibroma (page 35, line 13; page 37, line 6) or neurofibromatosis (page 27, line 6, line 11; page 35, line 5, line 13; page 36, line 29; page 38, line 12).
Liu does not teach treating cutaneous neurofibroma in a patient who has neurofibromatosis type 1, by administering to the patient nitroxoline, as in instant claim 3.
Dasgupta et al. (Cancer Res. 2005, 65 (21), 9843-9850) teach (Abstract) that individuals affected with the neurofibromatosis 1 (NF1) tumor predisposition syndrome are prone to the development of multiple nervous system tumors. Dasgupta teaches that MetAP2 is regulated by neurofibromin, and that MetAP2 inhibitors could be employed to treat NF1 associated tumor.
It would have been obvious for a person of ordinary skill in the art to use the teachings of Liu and Dasgupta to arrive at the instant invention. The person of ordinary skill in the art would have been motivated to administer nitroxoline to treat cutaneous neurofibroma in patients suffering from neurofibromatosis type 1, because Liu teaches that nitroxoline is a MetAP2 inhibitor effective to treat, for example, neurofibroma or neurofibromatosis, and Dasgupta teaches that MetAP2 inhibitors could be employed to treat NF1 associated tumor.
Thus, the person of ordinary skill in the art would have administered MetAP2 inhibitor nitroxoline to a subject suffering from neurofibromatosis type 1 and neurofibroma, or a subtype of neurofibroma which is cutaneous neurofibroma, with a reasonable expectation that the MetAP2 inhibitor is effective to treat NF1 associated tumor in such patients.
As such, claims 1, 3 are rejected as prima facie obvious.
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.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 3-17, 22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 22-39 of copending Application No. 18/710,477 (reference application) in view of Liu et al. (WO 2010/042163, cited in IDS). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 22-39 of copending Application No. 18/710,477 render obvious the instant claims.
Claims 22-39 of copending Application No. 18/710,477 are drawn to a method of treating or preventing a plexiform neurofibroma comprising administering to a subject in need thereof nitroxoline; claim 24 recites that the subject has neurofibromatosis type 1, as in instant claim 3; claim 25 recites that the subject is a human, as in instant claim 4; claims 26-32 recite amounts of nitroxoline administered and frequency of administration, as in instant claims 5-11; claims 33-34 refer to routes of administration of nitroxoline, as in instant claims 12, 13; claims 36-39 recite co-administering selumetinib, as in instant claims 15-17, 22.
Liu (WO 2010/042163) teaches that nitroxoline is effective to treat, for example, neurofibroma (page 35, line 13; page 37, line 6) or neurofibromatosis (page 27, line 6, line 11; page 35, line 5, line 13; page 36, line 29; page 38, line 12).
Treating neurofibromatosis is considered to at least prevent plexiform neurofibroma.
It would have been obvious for a person of ordinary skill in the art to use the teachings of claims 22-39 of copending Application No. 18/710,477 and Liu to arrive at the instant invention. The person of ordinary skill in the art would have been motivated to administer nitroxoline to treat cutaneous neurofibroma, because claims 22-39 of copending Application No. 18/710,477 teach that nitroxoline is effective to treat plexiform neurofibroma, and Liu teaches that nitroxoline effective to treat, for example, neurofibroma or neurofibromatosis. Thus, the person of ordinary skill in the art would have administered nitroxoline to a subject suffering from cutaneous neurofibroma, with a reasonable expectation that nitroxoline is effective against neurofibroma and the different subtypes of neurofibroma, such as cutaneous neurofibroma.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1, 3-17, 22 are rejected.
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/IRINA NEAGU/Primary Examiner, Art Unit 1629
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