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 1 July 2026, in which claim 20 has been amended, is acknowledged.
Claims 1-3, 5-8, 10-15, 17-23 are pending in the instant application.
Claims 22, 23 are withdrawn, as being drawn to a non-elected invention.
Claims 1-3, 5-8, 10-15, 17-21 are examined herein.
Response to arguments of 1 July 2026
In view of Applicant’s amendment of 1 July 2026, the objection to claims 22, 23 is herein withdrawn. The status indicators have been corrected.
In view of Applicant’s amendment of 1 July 2026, the rejection of claims 20, 21 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite, is herein withdrawn. The claim language has been clarified.
Applicant’s arguments (Remarks of 1 July 2026, pages 6-8) against the rejection of claims 1, 2, 5, 7, 8, 11, 13, 14, 15, 20 under 35 U.S.C. 102(a)(1) over Valls-Lacalle, have been considered.
The Declaration under 37 CFR 1.132, signed by Professor Thomas Krieg, co-inventor, submitted on 1 July 2026, has been considered.
Professor Krieg indicates (Declaration, points 5-6) that experimental work was carried out to directly compare the pH of the Valls-Lacalle infusion with the pH of the infusion of the instant Application. Disodium malonate 10 mM was added to the unbuffered physiological saline, in accordance with Valls-Lacalle. Professor Krieg states (Declaration, point 6) that addition of 10 mM disodium malonate to the physiological saline solution immediately increased the pH of the infusion, which stabilised at about pH 7.4 - 7.6. Thus, the disodium malonate in physiological saline composition used in Valls- Lacalle would have had a pH range 7.4 - 7.6.
In view of the data presented in the Declaration of 1 July 2026 (point 6), the rejection of claims 1, 2, 5, 7, 8, 11, 13, 14, 15, 20 under 35 U.S.C. 102(a)(1) over Valls-Lacalle is herein withdrawn.
A new/modified rejection is made below.
Applicant’s arguments (pages 8-13) against the rejection of claims 1-3, 5-8, 10-15, 17-21 under 35 U.S.C. 103 over Murphy, in view of Valls-Lacalle, have been considered.
Applicant argues (page 9) that Murphy demonstrates only that DMM is effective when administration commences before the onset of ischemia. This does not provide a possible clinical pathway for treating acute ischemic stroke, because in a clinical setting (such as in a hospital or ambulance) the medicament (DMM) could in practice only be administered after the onset of ischemia. In response, it is noted the instant claims are drawn to treating or preventing ischemia, which includes Murphy.
Applicant argues (page 9) that comparative Example 11, [0013], Figure 8, of the present application confirms that that DMM is not effective when administration commences after the onset of ischemia (i.e., when administration of DMM commences at or immediately prior to the onset of reperfusion). In response, it is noted the instant claims are not limited to administration of malonate at reperfusion (only claim 15 recites that).
Applicant further argues (page 11, third paragraph) that Murphy does not teach treating ischemia reperfusion with disodium malonate at pH 4 to 7, only with neutral ester compound which is dimethylmalonate. In response, Murphy is used in the rejection for the teaching that succinate dehydrogenase inhibitors are effective to treat reperfusion injury which is a result of reperfusion after stroke, or stroke and reperfusion injury, or myocardial ischemia, or ischemia that occurs during organ transplantation.
Applicant explains (page 10) that a key finding underpinning the present invention is that, surprisingly, artificially lowering the pH of an ischemic tissue dramatically enhances the intracellular delivery of salts of formula (I). Selective uptake of salts of formula (I) by ischemic tissue greatly increases the concentration of the compound accumulating in the tissue, which in turn reduces the extent of ischemia reperfusion injury ([0019]).
Examples 1 and 2 of the application as filed show that the intracellular delivery and uptake of disodium malonate (DSM) is greatly - and unexpectedly - enhanced in cells at pH 6 compared to cells at pH 7.4 and 8 (see Fig. 1 and Fig. 2). Applicant points to additional Examples presented in the Krieg declaration, showing enhanced intracellular delivery and uptake of salts across the scope of formula (I) and across the pH range of from about 4.0 to 7.0.
In response, the data in the Krieg Declaration, submitted on 1 July 2026, has been considered.
Professor Krieg argues (point 7) that
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In response, the instant claims are drawn to treating ischemia reperfusion injury. During myocardial ischemia, a large reduction of tissue pH develops, and tissue pH returns to normal after reperfusion (Lemasters et al. Myocardial Ischemia: Mechanisms, Reperfusion, Protection, 1996, p. 99, see below). Acidosis (pH <= 7.0) protects myocytes against cell death during ischemia. Thus, in the case of cardiac ischemia reperfusion, infusing an acidic solution directly to the tissue undergoing ischemia, before the onset of reperfusion, or at the point of reperfusion, would protect myocytes against cell death during ischemia.
Professor Krieg argues (Declaration points 8-10) that, while some intravenous drugs are infused from solutions at acidic pH, the reason for using low pH is due to the stability of the drug solutions on storage. Applicant argues that there are no infusions of drugs at low pH, where the low pH enhances the cell uptake or efficacy of the drug, as in the instant case.
This argument is not persuasive. What distinguishes the instant case from other drugs is the chemical structure of the drug. It is known that malonate is a dicarboxylate at physiological pH, with pKa1 = 2.83 and pKa2 = 5.69. The Henderson-Hasselbalch formula is used to calculate the species distribution of the fully protonated acid (H2M), monoacid (HM-) and fully deprotonated form M2- at different pH. Based on such calculations, a person of ordinary skill in the art would understand that at pH 7.0, 95% of the malonate is in the form of malonate anion M2-.
At pH = 5.69 = pKa2, 50% of the malonate is in the form of HM- and 50% is M2-.
At pH = 4, 91.9% of the malonate is in the form of monoacid (HM-).
Thus, a POSITA would expect that each pH, even within the range in instant claims 1, is associated with a different distribution of malonate forms (H2M), monoacid (HM-) and fully deprotonated form M2-.
The Declaration, point 11, shows that an increase in malonate uptake in C2C12 cells at pH = 4.0 versus pH 5, 6, or 7.0. Yet such increase in malonate uptake in the cells is in line with an increase in concentration of the monocarboxylic form monoacid (HM-), which represents 91% of the three forms at pH = 4.
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It is unclear how the data presented is relevant to the instant method of treating cardiac ischemia reperfusion, since C2C123 cells are distinct from cardiomyocytes.
Further, it is unclear how the data presented represents a side-by-side comparison with the closest prior art, which is Valls-Lacalle. Valls-Lacalle uses sodium malonate in saline, which Applicant has determined has a pH of 7.4. Thus, Valls-Lacalle teaches that sodium malonate in saline at pH = 7.4 is effective to treat ischemia reperfusion: when administered beginning at 39 min of ischemia and lasting for the first 5 min of reperfusion, intracoronary malonate at 10 mmol/L was effective to reduce infarct size.
Based on the data in Declaration point 11, the point of Applicant’s argument is that the malonate uptake into cells is important for efficacy, and the uptake depends on pH. Yet, at
pH = 7.0, which is within the range in instant claims, malonate exists almost entirely (over 95%) as fully deprotonated malonate ion M2-, comparable with 98% at pH = 7.4 (Valls-Lacalle). Applicant has not shown some unexpected result in treating ischemia at pH = 7.0, versus the method of Valls-Lacalle.
Regarding the establishment of unexpected results, a few notable principles are well settled. It is applicant’s burden to explain any proffered data and establish how any results therein should be taken to be unexpected and significant. See MPEP 716.02 (b). The claims must be commensurate in the scope with any evidence of unexpected results. See MPEP 716.02 (d). Further, A DECLARATION UNDER 37 CFR 1.132 must compare the claimed subject matter with the closest prior art in order to be effective to rebut a prima facie case of obviousness. See, MPEP 716.02 (e).
Applicant argues (page 12) that the data in Declaration shows that the uptake for disodium malonate, disodium succinate and disodium butylmalonate is greatly enhanced over the claimed pH 4 to 7. Applicant argues (page 13) that it is credible that the effect will be observed over the scope claimed.
In response, the point regarding pH and enhanced cellular uptake has been addressed above.
For all the reasons above, the rejection is maintained and modified rejections are made below.
For the same reasons, the rejections of the claims on the ground of nonstatutory double patenting are maintained.
Claims 1-3, 5-8, 10-15, 17-21 have been examined to the extent they read on the elected species, disodium malonate, which is a salt of formula (I)
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for which the following definitions apply:
Y = H; m = 0; n = 0;
X is a negative charge;
Z is Na+; A is 1; B is 2 (interview of 5 March 2026 with Mr. Rudy Ng, Attorney for Applicant), and the following objections and rejections are made below.
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 1-3, 5, 7, 8, 11, 13, 14, 15, 20, 21 are rejected under 35 U.S.C. 103 as obvious over Valls-Lacalle et al. (Scientific Reports 2018, 8, 2442, p. 1-9, published on line 5 February 2018, cited in IDS), in view of Lemasters et al. (Myocardial Ischemia: Mechanisms, Reperfusion, Protection, 1996, p. 99, Abstract, cited in PTO-892).
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 (Abstract) a method of treating cardiac ischemia reperfusion, to limit reperfusion injury and infarct size comprising administering to a subject in need thereof a composition in the form of solution for infusion, as in instant claim 5, comprising disodium malonate (Applicant’s elected species) in saline (page 7, last paragraph).
Disodium malonate is a malonate salt, as in instant claim 8, and is a salt of formula (I) of instant claim 1, where n is 0 and m is 0, as in instant claim 7.
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-Lacalle teaches intracoronary administration of disodium malonate, directly to the tissue undergoing ischemia, as in instant claim 13, where ischemia reperfusion injury is myocardial ischemia reperfusion injury, as in instant claim 11, with administration starting minutes before the onset of reperfusion, as in instant claim 14.
Valls-Lacalle does not teach that the pH of the malonate solution administered is 4.0 to 7.0, as in the instant claims.
Lemasters teaches (Summary) that during myocardial ischemia, a large reduction of tissue pH develops, and tissue pH returns to normal after reperfusion. Lemasters teaches that the role of pH in ischemia/reperfusion injury to cultured cardiac myocytes and perfused papillary muscles was investigated and it was found that acidosis (pH <= 7.0) protected profoundly against cell death during ischemia. Lemasters teaches that the return from acidotic to normal pH after reperfusion caused myocytes to lose viability. This worsening of injury is a 'pH paradox' and was mediated by changes of intracellular pH (pHi), since manipulations that caused pHi to increase more rapidly after reperfusion accelerated cell killing, whereas manipulations that delayed the increase of pHi prevented loss of myocyte viability.
It would have been obvious to a person of ordinary skill in the art to combine the teachings of Valls-Lasale and Lemasters to arrive at the instant invention. The person of ordinary skill in the art would have been motivated to prepare a solution of sodium malonate using a buffer to control the pH at 7.0 or lower, and administer said solution in the method of treating cardiac ischemia reperfusion taught by Valls-Lacalle, because
Lemasters teaches that during myocardial ischemia, a large reduction of tissue pH develops, and tissue pH returns to normal after reperfusion, and
Lemasters teaches that acidosis (pH <= 7.0) protected profoundly against cell death during ischemia, and manipulations that delayed the increase of intracellular pHi prevented loss of myocyte viability.
Thus, the person of ordinary skill in the art would have administered sodium malonate in a composition that has a pH of 7.0 or below, directly to the tissue undergoing ischemia, before the onset of reperfusion, or at the point of reperfusion, with the expectation that said administration will delay the increase of intracellular pH, and thus prevent loss of myocyte viability/protect against cell death during ischemia reperfusion.
Alternatively, it would have been obvious to prepare a neutral malonate solution buffered at
pH = 7.0, with a reasonable expectation that such a solution will retain therapeutic effect in the method of Valls-Lacalle. A prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. MPEP 2144.05.I.
As such, claims 1-3, 5, 7, 8, 11, 13, 14, 15, 20, 21 are rejected as prima facie obvious.
Claims 1-3, 5-8, 10-15, 17-21 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 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 6 recites that the reperfusion injury is ischemia reperfusion injury, as in the instant claims. Claim 7 recites that the reperfusion injury is a result, for example, of reperfusion after stroke, or stroke and reperfusion injury, as in instant claim 10. Murphy teaches (claim 10) treatment of reperfusion injury in organ transplantation, as in instant claim 12.
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 specifically teaches (page 35) that dimethyl malonate is effective to treat myocardial ischemia reperfusion injury, as in instant claim 11.
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 17, such as blood thinning agents, lysis agents, as in instant claims 18, 19.
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 ischemia reperfusion injury in a subject by administering disodium malonate in a composition having pH 4.0 to 7.0, 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 (Abstract) a method of treating ischemia reperfusion, to limit reperfusion injury and infarct size comprising administering to a subject in need thereof a composition in the form of solution for infusion, as in instant claim 5, comprising disodium malonate (Applicant’s elected species) in saline (page 7, last paragraph). Normal saline (0.9% NaCl) is a sterile, slightly acidic solution with a typical pH between 4.5 and 7.0, commonly cited as roughly 5.5, which is within the pH range in instant claims 1, 2, 20.
Disodium malonate is a malonate salt, as in instant claim 8, and is a salt of formula (I) of instant claim 1, where n is 0 and m is 0, as in instant claim 7.
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-Lacalle teaches intracoronary administration of disodium malonate, directly to the tissue undergoing ischemia, as in instant claim 13, where ischemia reperfusion injury is myocardial ischemia reperfusion injury, as in instant claim 11, with administration starting minutes before the onset of reperfusion, as in instant claim 14.
It would have been obvious to a person of ordinary skill in the art to administer sodium malonate salt to treat ischemic reperfusion injury, because Valls-Lacalle teaches that disodium 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 are effective to treat reperfusion injury which is a result of reperfusion after stroke, or stroke and reperfusion injury, or myocardial ischemia, or ischemia that occurs during organ transplantation. 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, or myocardial ischemia, or ischemia that occurs during organ transplantation, with the expectation of achieving therapeutic effect.
Further, the person of ordinary skill in the art would have administered sodium malonate as a solution for infusion, buffered at pH = 7.0, with pH close to saline vehicle used by Valls-Lacalle, with a reasonable expectation that such a solution will retain therapeutic effect. A prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. MPEP 2144.05.I.
The person of ordinary skill in the art would have used the schedule of administration taught by Valls-Lacalle, before/during reperfusion, with the expectation that such administration will result in therapeutic effect in treating reperfusion injury with disodium malonate.
As such, claims 1-3, 5-8, 10-15, 17-21 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, 5-8, 10-15, 17-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6-12, 14-20, 22-23 of U.S. Patent Application No. 17/781,297 (published as US 20220409562, 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 1-4, 6-12, 14-20, 22-23 of U.S. Patent Application No. 17/781,297 render obvious the instant claims.
Claims 1-4, 6-12, 14-20, 22-23 of U.S. Patent Application No. 17/781,297 are drawn to a method of treating ischemic stroke reperfusion injury in a subject with a salt of formula (I), wherein the genus of salts of formula (I) overlaps with the instant salts of formula (I). The pH of the composition comprising the salt of formula (I), administered in the method, is not disclosed.
Valls-Lacalle teaches (Abstract) a method of treating ischemia reperfusion, to limit reperfusion injury and infarct size, comprising administering to a subject in need thereof a composition in the form of solution for infusion, comprising disodium malonate in saline.
It would have been obvious to a person of ordinary skill in the art to administer disodium malonate as a solution for infusion, buffered at pH = 7.0, with pH close to saline vehicle used by Valls-Lacalle, in a method of claims 1-4, 6-12, 14-20, 22-23 of U.S. Patent Application No. 17/781,297, with a reasonable expectation that such a solution will retain therapeutic effect. A prima facie case of obviousness exists where the claimed ranges (in this case pH) or amounts do not overlap with the prior art but are merely close. MPEP 2144.05.I.
Claims 1-3, 5-8, 10-15, 17-21 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 (Abstract) a method of treating ischemia reperfusion, to limit reperfusion injury and infarct size, comprising administering to a subject in need thereof a composition in the form of solution for infusion, comprising disodium malonate in saline.
It would have been obvious to a person of ordinary skill in the art to administer disodium malonate as a solution, for infusion, as disclosed by Valls-Lacalle, in a method of treating a reperfusion injury in a subject, 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.
Further, the person of ordinary skill in the art would have administered sodium malonate as a solution for infusion, buffered at pH = 7.0, with pH close to saline vehicle used by Valls-Lacalle, with a reasonable expectation that such a solution will retain therapeutic effect. A prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. MPEP 2144.05.I.
Conclusion
Claims 1-3, 5-8, 10-15, 17-21 are rejected.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/IRINA NEAGU/Primary Examiner, Art Unit 1629
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