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 .
Election/Restrictions
Applicant’s election with traverse of Group I and species of a fully deuterated vinyl pyruvate (R1, R2, R3 = D; n = 0; and X1, X2, X3 = D) in the reply filed on July 22, 2026 is acknowledged.
The traversal is on the ground(s) that the claims which encompass invention Groups II and III, depend on claim 1, and include all the limitations of Group 1; and should therefore be eligible for examination together and do not impart an undue search burden.
This is not found persuasive because the claims in Groups II and III recite further limitations such as preparation steps, intermediates, solvents, and catalysts in addition to the limitations of Group I, and would therefore impose an undue search burden for examining together. Further, as discussed in the Office Action mailed June 4, 2026, Group II and III are drawn to two different methods for preparing the compound of Group I, and the technical feature of a compound of formula (III) does not represent a special technical feature over prior art. Thus, Groups I-III fail to satisfy the unity of invention requirement
The requirement is still deemed proper and is therefore made FINAL.
Claim Rejections - 35 USC § 112 New Matter
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 17 and 18 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
Claims 17 and 18 recite that the vinyl keto ester of formula (III) or vinyl pyruvate has a 13C atom specifically located at 1-13C, 1,2-13C or 2-13C. However, the specification as originally filed lacks any express or implicit disclosure defining formula (III) with isotopic labeling at these specific carbon positions. Applicant contends that because Scheme 2 of Example 1 of the specification discloses final products having a 1-13C, 1,2-13C or 2-13C atom, a skilled person will readily identify that the substrates to obtain said products also need to include a 1-13C, 1,2-13C or 2-13C atom. This argument is unpersuasive because the presence of a 1-13C, 1,2-13C or 2-13 label in a final product does not render it inevitable that the label originated from the starting material of formula (III). It is chemically plausible for isotopic labels to be introduced at intermediate synthetic stages. Speculative inference based on end-product structure without demonstrating that no other pathway exists cannot substitute for explicit disclosure. Therefore, the newly introduced limitation of a 13C atom specifically located at 1-13C, 1,2-13C or 2-13C, of formula (III) or vinyl pyruvate lacks written description support showing that the inventor was in possession of the claimed compound at the time of filing, and the claims constitute impermissible new matter that exceeds the scope of the original disclosure.
Amendment is required.
Claim Rejections - 35 USC § 112 Indefiniteness
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 1 and 16-18 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 1, the term "particularly" and the phrase ”more particularly” are ambiguous and optional language. Because it is unclear whether the limitations following these term and phrase are intended to be required features of the claimed invention, the term and phrase render the claim indefinite.
The dependent claims fall therewith.
Clarification and/or amendment is required.
Claim 16 recites “the compound of formula IV, VII, or of the moiety,” without proper antecedent basis in claim 1. Since claim 1 only covers “the compound of formula III,” it is unclear how claim 16 applies to formulas IV, VII, or the depicted moiety when dependent solely on claim 1. Specifically, it is unclear whether the moiety with open bonds attached to oxygen arm replaces existing functional groups of formula III or represents a separate compound family. Therefore, a person skilled in the art cannot determine the exact scope of the compound intended to be claimed in claim 16, rendering the claim indefinite. It is suggested that claim 16 be amended to delete “the compound of formula IV, VII, or of the moiety” to obviate this rejection.
Clarification and/or amendment is required.
Claim 17 recites the limitation “the 13C atom.” The claim lacks an antecedent basis for this limitation as claim 1 does not recite “a 13C atom.” Note that claim 16 recites “13C atom.” It is suggested that claim 17 be amended to depend on claim 16 to obviate this rejection. It is also suggested that claim 18 be amended to depend on claim 17.
Claim 17 also recites “1-13C, 1,2-13C or “2-13C.” The specification does not establish a clear position-numbering system for formula (III) that corresponds to “1-13C, 1,2-13C or “2-13C.” Relying on standard chemical nomenclature is insufficient because formula III encompasses variable structures (e.g., n is an integer from 0 to 16). The physical and chemical identity of position “2” changes depending on whether n = 0 or ≥ 1. Accordingly, without an explicit positional mapping in the specification, the terms ““1,2-13C” or “2-13C” render the scope of the claim indefinite. It is suggested that claim 17 be amended to recite the specific structural location of the 13C atom rather than using numerical positional identifiers to obviate this rejection.
Clarification and/or amendment is required.
Claim Rejections - 35 USC § 112 Improper Dependency
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 16 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 16 depends on claim 1. However, claim 16 further defines technical features regarding “the compound of formula IV, VII, or of the moiety,” which are not defined, disclosed, or recited in claim 1. A dependent claim must incorporate by reference all the limitations of the claim from which it depends and further limit that subject matter. Claim 16 introduces elements outside the scope of parent claim 1, failing to properly limit claim 1. It is suggested that claim 16 be amended to delete “the compound of formula IV, VII, or of the moiety” to obviate this rejection.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claims 1 and 16-18 are rejected under 35 U.S.C. 103 as being unpatentable over Vuichoud et al. (The Journal of Physical Chemistry B, 2014; cited on PTO-892) in view of Reineri et al. (Nature Communications, 2015; cited on PTO-892) and Hatano et al. (Organic Letters, 2016).
Vuichoud discloses the enhanced polarization of 13C nuclei in deuterated molecules such as [1-13C]pyruvate-d3
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for nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) system (abstract).
Vuichoud does not disclose a deuterated vinyl group attached to the pyruvate.
Reineri discloses a method of PHIP-SAH (parahydrogen-induced polarization by means of side arm hydrogenation) to overcome the limitation of PHIP (abstract; page 4, column 2, ¶ 2). Reineri discloses that PHIP can be obtained on molecules such as pyruvate by using precursors containing a side arm capable of hydrogenation that can be hydrolyzed to yield the hyperpolarized target products (page 4, column 2, ¶ 2). Reineri discloses that an unsaturated alcoholic group such as vinyl can be used as a side arm (page 5, column 1, ¶ 1).
Hatano discloses a method for H/D exchange of vinyl groups to prepare deuterium-labeled vinyl derivatives (abstract, page 3675, Scheme 2)
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. Hatano discloses that such deuterium-labeled compounds can be valuable for pharmaceutical applications (page 3674, column 1, ¶ 1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the [1-13C]pyruvate-d3 of Vuichoud by attaching the deuterium labeled vinyl group as a side arm in order to produce highly polarized pyruvate for fast and cost-effective metabolic MRI. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Reineri teaches that an unsaturated ester side arm such as vinyl can be attached to a target carboxylic acid such as pyruvate to yield hyperpolarized pyruvate effectively, and Hatano teaches a method for introducing D into a vinyl group to prepare deuterium-labeled vinyl derivatives. Further, a person of ordinary skill in the art would have been motivated to utilize deuterium-labelled vinyl group as a side-arm to produce a fully deuterated vinyl pyruvate (vinyl-[1-13C]pyruvate-d₆) as a precursor for PHIP-SAH to allow faster, simpler, and less expensive signal enhancement. The choice of specific isotopologues and isotopomers (D substitution) constitutes nothing more than the routine optimization of a known hyperpolarized imaging probe to maximize its physical and metabolic properties according to the specific requirements of the target applications in order to achieve an effective imaging agent.
Claims 1 and 16-18 are rejected under 35 U.S.C. 103 as being unpatentable over Carrera et al. (ChemPhysChem, 2021; cited on IDS filed December 18, 2023) in view of Vuichoud et al. (The Journal of Physical Chemistry B, 2014; cited on PTO-892) and Hatano et al. (Organic Letters, 2016).
Carrera discloses a vinyl-[1-13C]pyruvate as a hyperpolarized probe for imaging analysis (abstract). Carrera discloses a structure of a vinyl-[1-13C]pyruvate (page 1043, Scheme 1)
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, which corresponds to the elected species of compound of formula (III) of instant claims, except for the labeling with D.
Carrera does not disclose that the compound is fully deuterated.
AS discussed above, Vuichoud discloses the enhanced polarization of 13C nuclei in deuterated molecules such as [1-13C]pyruvate-d3
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for nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) system (abstract).
As discussed above, Hatano discloses a method for H/D exchange of vinyl groups to prepare deuterium-labeled vinyl derivatives (abstract, page 3675, Scheme 2)
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. Hatano discloses that such deuterium-labeled compounds can be valuable for pharmaceutical applications (page 3674, column 1, ¶ 1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the vinyl-[1-13C]pyruvate of Carrera by labeling the compound with D as taught by Vuichoud and Hatano to produce a vinyl-[1-13C]pyruvate-d₆. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Vuichoud teaches that methyl group with D can be used in the pyruvate compound for MRI and Hatano teaches a method for introducing D into a vinyl group to prepare deuterium-labeled vinyl derivatives. Further, a person of ordinary skill in the art would have been motivated to utilize a vinyl-[1-13C]pyruvate-d₆ as a precursor for PHIP-SAH to optimize spin physics, allowing for higher nuclear polarization levels and cleaner transfer of spin order. The choice of specific isotopologues and isotopomers (D substitution) constitutes nothing more than the routine optimization of a known hyperpolarized imaging probe to maximize its physical and metabolic properties according to the specific requirements of the target applications in order to achieve an effective imaging agent.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JONG HWAN BAEK whose telephone number is (571)272-0670. The examiner can normally be reached Mon - Thu, 9 am - 3 pm ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael G Hartley can be reached at 571-272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JONG HWAN BAEK/Examiner, Art Unit 1618
/Michael G. Hartley/ Supervisory Patent Examiner, Art Unit 1618
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