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 11 November 2022, in which claims 1-4, 6-12, 14-20, 22-23 have been amended, and claims 5, 13, 21, 24-25 have been cancelled, is acknowledged.
Claims 1-4, 6-12, 14-20, 22-23 are pending in the instant application.
Claims 1-4, 6-12, 14-20, 22-23 are examined herein.
Priority
The instant application is a National stage entry on International Patent Application PCT/GB2020/053141, filed on 8 December 2020, which claims priority from GB Patent Application No. 1918022.3, filed on 9 December 2019. A certified copy of the priority document has been submitted on 31 May 2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11 November 2022 is acknowledged and considered.
Election/Restrictions
Applicant’s election without traverse of malonate salts as the species of a salt of formula (I) administered in the method of treatment, for initial examination, in the reply filed on 10 November 2025, is acknowledged. Claims 1-4, 6-12, 14-20, 22-23 read on the elected species.
Applicant’s elected species, malonate, is a salt of formula (I)
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for which the following definitions apply:
Y = H; m = 0; n = 0.
Since Applicant set forth no arguments against the requirement for election of species, the requirement for restriction/election is herein maintained and is made FINAL.
Claims 1-4, 6-12, 14-20, 22-23 have been examined to the extent they read on the elected species and the following objections and rejections are made below.
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.
Claims 12, 20 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 12 recites the broad recitation “administration […] before reperfusion”, and the claim also recites “preferably […] administered at least 10 minutes before the onset of reperfusion”, which is the narrower statement of the range/limitation.
Further, claim 20 recites the broad recitation “dosage in the range of from about 0.1 mg/kg to about 500 mg/kg of body weight”, and the claim also recites “preferably in the range of from about 0.5 mg/kg to about 100 mg/kg of body weight”, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Appropriate clarification is required.
Claims 7, 19 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.
In claim 7, the phrase “selected from Li+, Na+, […] and/or NH4+” is vague and indefinite because the term “or NH4+” would mean that the claim is open ended in the closed Markush expression “selected from the group consisting of”.
Similarly, in claim 19, the phrase “selected from thrombolysis [by application of blood thinning agents or application of lysis agents], and/or thrombectomy” is vague and indefinite because the term “or thrombectomy” would mean that the claim is open ended in the closed Markush expression “selected from the group consisting of”.
Appropriate clarification is required.
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 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 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 1-4, 6-12, 14-20, 22-23 are rejected under 35 U.S.C. 103 as obvious over Murphy et a. (WO 2016/001686, cited in IDS), in view of Valls-Lacalle et al. (Scientific Reports 2018, 8, 2442, p. 1-9, published on line 5 February 2018, cited in IDS).
Murphy teaches a method for treating a reperfusion injury in a subject, the method comprising administering to the subject a therapeutically effective amount of a cell-permeable and reversible succinate dehydrogenase inhibitor (SDHi) or a prodrug, or a pharmaceutically acceptable salt thereof, such as, for example, dimethyl malonate (Claim 5). Claim 7 recites that the reperfusion injury is a result, for example, of reperfusion after stroke, or stroke and reperfusion injury.
Murphy specifically teaches (page 36, last paragraph) that dimethyl malonate is effective to treat ischemic reperfusion injury in vivo in a rat brain ischemia and reperfusion model.
Murphy teaches (page 14, lines 19-25) that a SDHi or a prodrug or a pharmaceutically acceptable salt of the invention may be administered in combination with a treatment used to remove a blockage in blood flow, as in instant claim 18, such as blood thinning agents, lysis agents, as in instant claim 19.
Murphy teaches that the method is used in combination therapy to prevent tissue damage, as in instant claim 22.
Murphy teaches (page 24, Figure 4(d)) protection by dimethylmalonate against brain I/R injury in vivo, with quantification of brain infarct volume. This is consistent with dimethyl malonate being effective to treat brain injury upon ischemic reperfusion injury, consistent with dimethyl malonate being brain penetrant.
Murphy does not teach a method of treating ischemic stroke reperfusion injury in a subject by administering disodium malonate, as in the instant claims.
Valls-Lacalle teaches (Abstract) that disodium malonate is a selective inhibitor a succinate dehydrogenase effective to treat ischemia reperfusion, limit reperfusion injury and infarct size.
Valls-Lacalle teaches that malonate was administered beginning at 39 min of ischemia and lasting for the first 5 min of reperfusion (page 8, second paragraph); intracoronary malonate at 10 mmol/L was effective to reduce infarct size.
Thus, Valls-Lcalle teaches administering sodium malonate salt during reperfusion, as in instant claim 14, with administration starting minutes before the onset of reperfusion, as in instant claim 12, for a total time as in instant claim 17.
It would have been obvious to a person of ordinary skill in the art to administer sodium malonate salt to treat ischemic stroke reperfusion injury, because Valls-Lacalle teaches that sodium malonate is a selective inhibitor a succinate dehydrogenase effective to treat ischemia reperfusion, limit reperfusion injury and infarct size, and claims Murphy teaches that succinate dehydrogenase inhibitors such as methyl malonate are effective to treat reperfusion injury which is a result of reperfusion after stroke, or stroke and reperfusion injury. Thus, a person of ordinary skill in the art would have administered sodium malonate salt to a subject suffering from reperfusion injury due to stroke, with the expectation of achieving therapeutic effect.
Further, regarding claims 10, 11, the person of ordinary skill in the art would have administered sodium malonate intravenously, and, would have determined the therapeutically effective dose, as in instant claim 20, because determining the optimal administration route and the therapeutic dose in a method of treatment is routine, well within the skill of the artisan.
The person of ordinary skill in the art would have used the schedule of administration taught by Valls-Lacalle, before/during reperfusion, before stroke, with the expectation that such administration will result in therapeutic effect in treating reperfusion injury with disodium malonate.
As such, claims 1-4, 6-12, 14-20, 22-23 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 1-4, 6-12, 14-20, 22-23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent Application No. 18/568,243 (published as US 2024/0252457, cited in PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-25 of U.S. Patent Application No. 18/568,243 render obvious the instant claims.
Claims 1-21 of U.S. Patent Application No. 18/568,243 are drawn to composition comprising a salt of formula (I)
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,
wherein the genus of salts of formula (I) overlaps with the instant salts of formula (I). Claims 22, 23 are drawn to a unit dosage form for intravenous infusion comprising a composition comprising a salt of formula (I), and claim 23 is drawn to a kit comprising a composition comprising a salt of formula (I). The Specification of U.S. Patent Application No. 18/568,243 teaches that salt of formula (I) are effective to treat ischemia reperfusion injury in a subject. Claims 24, 25 of U.S. Patent Application No. 18/568,243 are drawn to a method of treating ischemia reperfusion injury in a subject with a salt of formula (I).
As such, there is substantial overlap between the method of the instant claims and the method and composition of claims 1- 25 of U.S. Patent Application No. 18/568,243.
Claims 1-4, 6-12, 14-20, 22-23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 10,603,298 (cited in PTO-892), in view of Valls-Lacalle et al. (Scientific Reports 2018, 8, 2442, p. 1-9, published on line 5 February 2018, cited in IDS). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-13 of U.S. Patent No. 10,603,298 render obvious the instant claims.
Claims 1-13 of U.S. Patent No. 10,603,298 are drawn to a method for treating a reperfusion injury in the heart of a subject, the method comprising administering to the subject a therapeutically effective amount of a cell-permeable and reversible succinate dehydrogenase inhibitor that is, for example, dimethyl malonate (Claim 3). Claim 4 recites that the reperfusion injury is a result, for example, of reperfusion after stroke, or stroke and reperfusion injury.
Claims 1-13 of U.S. Patent No. 10,603,298 do not teach the method by administering sodium malonate, as in the instant claims.
Valls-Lacalle teaches that sodium malonate is a selective inhibitor a succinate dehydrogenase effective to treat ischemia reperfusion, limit reperfusion injury and infarct size.
It would have been obvious to a person of ordinary skill in the art to administer sodium malonate salt to treat ischemic stroke reperfusion injury, because Valls-Lacalle teaches that sodium malonate is a selective inhibitor a succinate dehydrogenase effective to treat ischemia reperfusion, limit reperfusion injury and infarct size, and claims 1-13 of U.S. Patent No. 10,603,298 teach that succinate dehydrogenase inhibitors such as methyl malonate are effective to treat reperfusion injury which is a result of reperfusion after stroke, or stroke and reperfusion injury. Thus, a person of ordinary skill in the art would have administered sodium malonate salt to a subject suffering from reperfusion injury due to stroke, with the expectation of achieving therapeutic effect.
Conclusion
Claims 1-4, 6-12, 14-20, 22-23 are rejected.
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/IRINA NEAGU/Primary Examiner, Art Unit 1629