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 Claims
Claims 1-40 are pending. Acknowledgment is made of Applicant’s preliminary amendments filed on May 06, 2024.
Priority
This application claims priority to U.S. Provisional Application No. 63/276,748, filed November 08, 2021, and is a 371 of PCT/US2022/049131, filed November 07, 2022.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 32-36 are rejected under 35 U.S.C. 101 because the claimed invention is not supported by either a specific and substantial asserted utility or a well-established utility.
Claims 32-36 recite the use of a compound of according to the formula in claim 1 for the manufacture of a medicament for treating pain. However, this is not a specific utility, as it is unclear whether these claims are drawn to a method for the manufacture of a medicament comprising a compound of claim 1, a medicament for treating pain comprising a compound of claim 1, or a method of treating pain using a medicament comprising a compound of claim 1. Thus, the claimed invention is not supported by a specific utility.
Claim Rejections - 35 USC § 112
112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 32-36 are also rejected under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph. Specifically, because the claimed invention is not supported by either a specific and substantial asserted utility or a well-established utility for the reasons set forth above, one skilled in the art clearly would not know how to use the claimed invention.
112(b)
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 32-36 are 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 pre-AIA the applicant regards as the invention.
Claims 32-36 are directed to a compound for use in the manufacture of a medicament for treating pain. It is unclear whether the claims are intending to encompass a product (i.e. a medicament for treating pain comprising a compound according to claim 1) or method/process of utilizing the claimed product or in a process of making other compositions (i.e. a process of manufacturing a medicament for treating pain comprising a compound according to claim 1).
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 1-31 and 37-40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 5, 9-12 and 15-25 of U.S. Patent No. 11,414,389 B2 (cited in the IDS filed May 06, 2024) in view of Pirali et al. (J. Med. Chem. 2019, 62, 5276-5297) and Liu et al. (Annual Reports in Medicinal Chemistry 2017, 50, 519-542).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been obvious over the above-mentioned claims of US 11,414,389 B2.
US 11,414,389 B2 claims compounds of the following formula and pharmaceutically acceptable salts thereof (claim 1).
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408
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In specific embodiments, US 11,414,389 B2 teaches the following compounds of claim 1:
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(claim 15)
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(claim 17).
US 11,414,389 B2 also claims a method of administering the above compounds to treat pain in a patient (claim 19), chronic pain (claim 20), chronic lower back pain (claim 21), diabetic peripheral neuropathic pain (claim 22), and osteoarthritis pain (claim 23). Finally, US 11,414,389 B2 claims a pharmaceutical composition comprising one of the above compounds (claim 24) as well as a process for preparing such a pharmaceutical composition (claim 25).
US 11,414,389 B2 does not claim compounds wherein the methyl is deuterated.
Pirali teaches deuterium is a rare, stable, nonradioactive isotope of hydrogen, which differs from protium by a single neutron (page 5276, left, para. 1); deuterium-modified compounds usually retain biochemical potency and selectivity (p. 5277, left para. 3), the most straightforward application of deuterium substitution is to slow down drug metabolism, especially cytochrome P450 (CYP450)-mediated transformations (page 5278, left, para. 1); ample literature is devoted to deuteration as a means to improve the PK profile of drugs (page 5278, right, para. 2); independent of PK parameters, deuteration of a soft-spot can be capitalized upon to reduce the formation of unwanted metabolites, as well as to increase the formation of desirable active metabolites, a phenomenon named metabolic shunting (page 5281, right, para. 3); the substitution of the acidic proton with deuterium at the chiral center of a single stereoisomer might decrease the rate of atom abstraction and afford a good strategy to stabilize chemically unstable stereoisomers (page 5283, right, para. 3); and deuteration can also be used as a means to expand knowledge, for example, to test the contribution of a metabolite to the action of a particular drug (page 5284, left, para. 3). Thus, Pirali teaches deuterium substitution is a known method utilized in drug design and known for use in improving bioavailability, drug stability, and PK profile while retaining biochemical potency and selectivity.
Pirali does not teach the deuteration of methyl to lower the required dose.
Liu teaches the broad proposition for deuterium substitution in drug discovery is that if a drug is quickly metabolized via enzymatic cleavage of a C–H bond, and if this cleavage is at least partially rate-limiting, a deuterium isotope effect (DIE) may potentially slow the reaction kinetics and increase the metabolic stability of an appropriately deuterated drug, which could lead to lower efficacious doses (p. 521, para. 2). In particular, Liu teaches deuteration of the methyl groups in dextromethorphan substantially lowers the dose of quinidine needed to be co-administered (pp. 527-528, 2nd para. of 527 into 1st para. of 528).
Regarding claims 1-20, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to produce a deuterium enriched compound from US 11,414,389 wherein the hydrogens on methyl moieties are substituted with deuterium to arrive at the instantly claimed compounds. One would have been motivated and had a reasonable expectation of success to do so since Pirali teaches deuterium substitution is a known method in drug design for use in improving bioavailability, drug stability, and PK profile and Liu teaches deuterium substitution of methyl in drugs can lower the required dose.
Regarding claims 21-25, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to administer compounds from US 11,414,389 wherein the hydrogens on methyl moieties are substituted with deuterium to treat pain (as well as chronic pain, chronic lower back pain, diabetic peripheral neuropathic pain, and osteoarthritic pain) in a subject. One would have been motivated and had a reasonable expectation of success to do so since US 11,414,389 teaches the non-methylated compounds treat pain and the prior art teaches substitution of deuterium usually retains biochemical potency and selectivity.
Regarding claim 26, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to produce compounds of the formula in instant claim 1 for use in therapy since the prior art teaches the non-deuterated compounds of instant claim 1 can be used in treating pain and substitution of deuterium usually retains biochemical potency and selectivity, and because treating pain is a form of therapy.
Regarding claims 27-31, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to produce compounds of the formula in instant claim 1 for use in therapy since the prior art teaches the non-deuterated compounds of instant claim 1 can be used in treating pain (as well as chronic pain, chronic lower back pain, diabetic peripheral neuropathic pain, and osteoarthritic pain) and substitution of deuterium usually retains biochemical potency and selectivity.
Regarding claims 37-39, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to produce a pharmaceutical composition comprising a compound according to claim 1 since the prior art teaches a pharmaceutical composition of the non-deuterated form of the same compounds.
Regarding claim 40, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to prepare a pharmaceutical composition comprising a compound according to claim 1 since the prior art teaches the same process of preparing a pharmaceutical composition except with the non-deuterated form of the same compounds from instant claim 1.
Taken altogether, all this would result in the invention of instant claims 1-31 and 37-40 with a reasonable expectation of success. In other words, the invention of instant claims 1-31 and 37-40 are obvious over the invention of claims 1, 3, 5, 9-12 and 15-25 of US 11,414,389 B2. Thus, instant claims 1-31 and 37-40 are not patentably distinct from the invention of claims 1, 3, 5, 9-12 and 15-25 of US 11,414,389 B2.
Conclusion
Claims 1-40 are rejected.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to OLIVER D. HEES whose telephone number is (571)272-9840. The examiner can normally be reached Monday - Friday 8:00 am - 5:00 pm.
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/O.D.H./ Examiner, Art Unit 1628
/AMY L CLARK/ Supervisory Patent Examiner, Art Unit 1628
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