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, 10, 13-16, 19, 22, 25, 28-32, 35-38, and 40-41 are pending. Claims 35-38 and 40-41 are withdrawn. Claims 1, 10, 13-16, 19, 22, 25, and 28-32 are rejected.
Information Disclosure Statement
The Information Disclosure Statement (IDS) submitted on 7/26/2024 was considered by the Examiner.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1, 10, 13-16, 19, 22, 25, and 28-32) in the reply filed on 8/10/2026 is acknowledged.
Claims 35-38 and 40-41 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claim Interpretation
Regarding instant claim 15, Examiner is interpreting the following “wherein” clauses as only limiting “a compound” and not the whole “isotopic mixture”:
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. Therefore, only one compound in a mixture is required to have the limitations of the wherein clauses shown here.
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.
Claim 32 is 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.
Claim 32 preamble is drawn to a product claim: “[t]he pharmaceutical composition] and the body of the claim is drawn to “for use in a method” and “the method”. Consequently, it is unclear if the claim is a product or method claim. In the interest of compact prosecution and due to the nature of the preamble, the claim is being interpreted as a product claim in this office action.
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.
Claim 1 is rejected under 35 USC 101 because the claimed invention is directed to a product of nature (law of nature or natural phenomenon) without significantly more. Subject matter eligibility guidance from MPEP 2106 requires considering the following steps:
Step 1: the claims are to a chemical compound of Formula (I) product. (Step 1: Yes).
Step 2A, prong one: alpha-ketoglutarate is a nature-based product because it is an essential metabolite, as evidenced by Legendre et al. (World Journal of Microbiology and Biotechnology, 2020, 36:123). Legendre specifically teaches the following in the abstract:
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The markedly different characteristics analysis is used to determine if the nature-based product is a product of nature exception. MPEP2106.04(C)(I). The compound of the claims is a metabolite that occurs in “virtually all organisms”. Therefore, the naturally occurring counterpart is the compound as it occurs in nature inside an organism. Upon comparing the claimed product to the naturally occurring counterpart, the comparison shows there are not differences in chemical structure or any other aspect of characteristic. The isotopes of carbon-13 and deuterium of the instant claims occur in nature to varying degrees and abundances (natural phenomenon).
Step 2A, prong two: This part of the eligibility analysis evaluates whether the claim as a whole integrates the recited judicial exception in a practical application of the exception. This evaluation is performed by (a) identifying whether there are any additional elements recited in the claim beyond the judicial exception, and (b) evaluating those additional elements individually and in combination to determine whether the claim as a whole integrates the exception into a practical application. The claims do not recite language which integrates the exception into a practical application. (Step 2A: No).
This part of the eligibility analysis evaluates whether the claim as a whole amounts to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim. MPEP 2106.05. As discussed with respect to Step 2A Prong Two, the claim does not recite any additional element beyond the judicial exception. Thus, the claims lack an inventive step (Step 2B: No). The claim is not eligible.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1, 10, 13, 15, 16, 19, 22, 25, 28 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by CAS Registry No. 1381759-60-9 (which entered the STN database on 7/5/2012).
Regarding instant claims 1, 10, 13, 15, 16, 19, 22, 25, 28, CAS Registry No. 1381759-60-9 is drawn to the following structure:
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, which is embraced by a compound of instant Formula (I):
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wherein Xa-Xd are deuterium [at least 25% and at least 50% of the sum of Xa-Xd are deuterium]; R1 = H. Regarding carbon number 1 of the instant claims, the prior art compound would inherently comprise an isotope of carbon-13. Regarding instant claims 13 and 28, the prior art compound would inherently comprise deuterium instead of hydrogen because of deuterium’s natural abundance. Regarding instant claim 15, an isotopic mixture would be inherent because of carbon and hydrogen isotope natural abundance. Additionally regarding instant claim 15, the claimed composition only requires an isotopic mixture of a compound of Formula (I), which is embraced by the prior art compound above and isotope natural abundances.
Claim(s) 1, 10, 13, 15, 16, 19, 22, 25, 28, 30-32 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chaumeil et al. (Nature Com.; published 2013; 4(2429), 1-23; see IDS filed 26 Jul. 2024).
Regarding claims 1, 10, 13, 15, 16, 19, 22, 25, 28, Chaumeil et al. disclose a [1-13C]α-ketoglutarate composition that comprises 1-13C-5-12C alpha ketoglutarate
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(see Fig. 1; pg. 16), which is embraced by a compound of instant formula (I):
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, wherein R1 both = H (may be deuterium because of natural abundance); Xa-Xd = H (each may be deuterium because of natural abundance). Specifically, regarding instant claim 15, the claimed composition only requires an isotopic mixture of a compound of Formula (I), which is embraced by the prior art compound above.
Regarding claims 30-31, Chaumeil et al. teach the following on p. 3:
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wherein water and glycerol are pharmaceutically acceptable carriers for the hyperpolarized compound of [1-13C]α-ketoglutarate (composition of instant claim 31 only requires an isotopic mixture of said compound). Regarding instant claim 32 (rejected as indefinite above), in which the preamble is drawn to “[t]he pharmaceutical composition of claim 30”, the prior art described herein would be intrinsically capable of any use or method because it is has the same structure as claimed.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 14 and 29 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chaumeil et al. (Nature Com.; published 2013; 1-12; see IDS filed 26 Jul. 2024), as applied to claims 1, 10, 13, 15, 16, 19, 22, 25, 28, 30-32 above, and further in view of Paulekuhn et al. (J. Med. Chem, 2007-cited on 7/26/2024 IDS).
**The 102 rejection of claims 1, 10, 13, 15, 16, 19, 22, 25, 28, 30-32 over Chaumeil supra is incorporated herein by reference.
Chaumeil fails to teach when R1 is a cation. Paulekuhn provides for this deficiency.
Paulekuhn teaches that salt formation is “a well-known technique to modify and optimize the physical chemical properties of an ionizable research or development compound. Properties such as solubility, dissolution rate, hygroscopicity, stability, impurity profiles, and crystal habit can be influenced by using a variety of pharmaceutically acceptable counterions” (see p. 6665, left column). Regarding instant claims 14 and 29, it would have been obvious to a skilled artisan to modify an anticipated compound with R1 being a cation, which would result from salt formation. A PHOSITA would have been motivated to transform [1-13C]α-ketoglutarate into a salt, wherein R1 would be a cation, to improve physical and chemical properties such as solubility and stability. A skilled artisan would have arrived at a salt of [1-13C]α-ketoglutarate with a reasonable expectation of a useful compound.
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, 10, 13-16, 19, 22, 25, and 28-32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 3 and 5-27 of copending Application No. 17793089, in view of Chaumeil et al. (Nature Com.; published 2013; 4(2429), 1-23; see IDS filed 26 Jul. 2024).
The co-pending case teaches the following in claims 3 and 5:
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Regarding instant claims 1, 10, 13, 15, 16, 19, 22, 25, and 28, which are drawn to
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, wherein hydrogen may be deuterium at any location due to natural abundance. Regarding instant claims 14 and 29, R1 would be a cation when the co-pending case compound shown supra is the pharmaceutically acceptable salt thereof. Specifically, regarding instant claim 15, the claimed composition only requires an isotopic mixture of a compound of Formula (I), which is embraced by the co-pending case compound above.
Regarding claims 30-31, Chaumeil et al. teach the following on p. 3:
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wherein water and glycerol are pharmaceutically acceptable carriers for the hyperpolarized compound of [1-13C]α-ketoglutarate (composition of instant claim 31 only requires an isotopic mixture of said compound). Regarding instant claim 32 (rejected as indefinite above), in which the preamble is drawn to “[t]he pharmaceutical composition of claim 30”, the prior art described herein would be intrinsically capable of any use or method because it is has the same structure as claimed and is a “version” of the co-pending case compound.
This is a provisional nonstatutory double patenting rejection.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MEGHAN C HEASLEY whose telephone number is (571)270-0785. The examiner can normally be reached Monday - Friday 8:30-4:30 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy Clark can be reached at 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MEGHAN C HEASLEY/Examiner, Art Unit 1626
/KAMAL A SAEED/Primary Examiner, Art Unit 1626
