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 Application
Claims 1-2, 7, 11-15, 17, 20-22, 37-38, 41-42, 46-47, 49 and 51-54 are pending in the application as of the preliminary amendment submitted 09/09/2024. Claims 3-6, 8-10, 16, 18-19, 23-36, 39-40, 43-45, 48 and 50 are cancelled. Claims 1-2, 7, 11-15, 17, 20-22, 37-38, 41-42, 46-47, 49 and 51-54 are examined herein.
Priority
This application is a 371 of PCT/US2022/028488 filed 05/10/2022 and claims foreign priority to JAPAN 2021-079820 filed 05/10/2021.
It is noted that Applicants have not provided an English translation of the certified copy of the foreign priority application as required by 35 U.S.C. 119(b). Without the English translation, one cannot ascertain if the instant invention is supported in the Japanese application. Therefore, art prior to the PCT date, but not before the date of the Japanese application may be cited against the claims. Accordingly, claims 1-2, 7, 11-15, 17, 20-22, 37-38, 41-42, 46-47, 49 and 51-54 have been afforded an effective filing date of 05/10/2022, the filing date of the PCT application.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e). Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Information Disclosure Statement
The information disclosure statements submitted on 10/31/2025, 09/09/2024 and 01/09/2024 (2) are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
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 47 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.
Regarding claim 47, the claim recites the limitations “wherein the basic additive is one or more selected from the group consisting of amino sugars, alkanolamines and trometamol salts, preferably, … the amphipathic additive is one or more selected from the group consisting of polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan monolaurate, polyoxyethylene-polyoxypropylene glycol, polysorbate, polyethylene glycol, ursodesocycholic acid, sorbitan fatty acid ester and sodium desoxycholate, preferably …”.
The recitation of the limitation “preferably” renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Thus, the metes and bounds of the claims are unclear.
For the purpose of applying prior art, claim 47 has been interpreted to
exclude the language that follows the limitation “preferably”.
Claim Rejections - 35 USC § 102
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 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.
Claims 20-21, 37, 38 and 54 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Honda et al. (EP 2452679 A1, 16 May 2012, hereinafter Honda, in the IDS).
Regarding instant claims 20-21, Honda teaches a method of treatment of ischemic damage including administration of a drug containing a triprenyl phenol compound according to the present invention to a patient 3 or more hours after the onset of a symptom, especially for the treatment of cerebral infraction (Para. [0081]). Honda further teaches administration of the agent up to 12 hours after the onset of the symptom (Para. [0069]). Honda teaches the subject can be a human (Para. [0076]). Honda exemplifies the treatment of cerebral infarction in various animal models comprising administering an exemplary triprenyl phenol compound, SMTP-7 (Paras. [0085]-[00173]). SMTP-7 is taught to be a cryoprotective agent for the treatment of ischemic damage having the following structure (Paras. [0008]-[0010]; Paras. [0060]-[0061], Table 5).
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Honda teaches the triprenyl phenol compounds to have plasminogen activation activity which allows for thrombolysis, as well as cryoprotective effect for inhibiting dysfunction caused by ischemia (Paras. [0006]-[0007]; Para. [0017]). SMTP-7 is Compound I of instant claim 1 as evidenced by Para. [0008] of the instant specification.
According to MPEP 2131.02(III), “A reference disclosure can anticipate a claim when the reference describes the limitations but "'d[oes] not expressly spell out' the limitations as arranged or combined as in the claim, if a person of skill in the art, reading the reference, would ‘at once envisage’ the claimed arrangement or combination." Kennametal, Inc. v. Ingersoll Cutting Tool Co., 780 F.3d 1376, 1381, 114 USPQ2d 1250, 1254 (Fed. Cir. 2015) (quoting In re Petering, 301 F.2d 676, 681(CCPA 1962))”. In the instant case, the method of treating cerebral infarction in a human as in instant claim 1 can be clearly envisaged by a person of ordinary skill in the art, given the disclosure of Honda. Therefore, the teachings of Honda anticipate the limitations of instant claims 20-21.
Regarding instant claim 37, Honda anticipates the method of treating a human subject with cerebral infarction, comprising administering to the human subject in need thereof a pharmaceutical composition comprising Compound I having the structure of formula (I). The limitation with respect to “wherein the administering of the pharmaceutical composition recanalizes occluded vessel in cerebral infarction”, is related to the mechanism of action of the drug, Compound I, in treating cerebral infarction. Honda teaches the active step of administering a pharmaceutical composition of the same drug (Compound 1) to the same patient population (a subject with cerebral infarction).
According to MPEP 2112.02 (II), “The discovery of a new use for an old structure based on unknown properties of the structure might be patentable to the discoverer as a process of using. In re Hack, 245 F.2d 246, 248, 114 USPQ 161, 163 (CCPA 1957). However, when the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978)”. In the instant case, the method of Honda, when practiced in treating a human subject with cerebral infarction, would have necessarily produced the same treatment effects. Therefore, the limitations of instant claim 37 are anticipated by the disclosure of Honda.
Regarding instant claims 38 and 54, Honda anticipates the method of treating a human subject with cerebral infarction, comprising administering to the human subject in need thereof a pharmaceutical composition comprising Compound I having the structure of formula (I). Honda further teaches in case of cerebral infarction, it would be effective to use the cryoprotective agent for a patient to whom a thrombolytic drug cannot be administered, because the risk of intracranial hemorrhage would be increased (Para. [0074]; Para. [0082]). Therefore, the disclosure of Honda anticipates the limitations of instant claims 38 and 54.
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.
Claims 1-2, 7, 11-12, 15, 20-22, 37, 41-42, 49 and 51-53 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nishimura et al. (Abstract WMP1: Results From A Phase 2a Study Of TMS-007, An SMTP Family Anti-inflammatory Prothrombolytic, On Patients With Acute Ischemic Stroke Up To 12 Hours After Onset, 03 February 2022, hereinafter Nishimura).
Applicants may overcome this rejection by perfecting the foreign priority filing date. According to MPEP 2152.06(C), “The filing date of the priority document is not perfected unless applicant has filed a certified priority document in the application (and an English language translation, if the document is not in English) (see 37 CFR 1.55(g))”.
Regarding instant claims 1-2, 11 and 49, Nishimura teaches TMS-007 a small molecule SMTP family member with a novel mode of action: promotion of plasminogen-fibrin binding to enhance physiological thrombolysis while inhibiting inflammation at the site of thrombosis (Abstract). Nishimura teaches TMS-007 administered as a single intravenous infusion at a dose of 1, 3, or 6 mg/kg to acute ischemic stroke (AIS) patients who were ineligible for t-PA or thrombectomy within 12 h of LKN (Abstract). Para. [0008] and Para. [0063] of the instant specification evidences TMS-007 to be a sodium salt preparation of SMTP-7, i.e., Compound I of the instant claims. Nishimura teaches the active step of administering a pharmaceutical composition of the same drug (Compound 1) to the same patient population (a subject who has experienced acute ischemic stroke, that would lead to cerebral infarction). Therefore, Nishimura anticipates the method of instant claims 1-2, 11 and 49.
Nishimura further teaches TMS-007 can extend the treatment window beyond 4.5 h since last known normal (LKN), unlike most other approved thrombolytic agents in the treatment of AIS (Abstract). Nishimura teaches TMS-007 was associated with a significant improvement in functional independence at 90 days (secondary endpoint): 40% of patients in Group T achieved a score of 0 or 1 on the mRS, compared to 18% in Group P (p < 0.05) (Abstract). Nishimura teaches recanalization occurred in 58.3% (14/24) of Group T compared to 26.7% (4/15) of Group P (odds-ratio, 4.23; 95% CI, 0.99 to 18.07) (Abstract).
The disclosure of Nishimura further anticipates the limitations of instant claims 7, 12, 15, 20-22, 37, 41-42.
Regarding the limitations of instant claims 51-53 drawn to “wherein the administering of the pharmaceutical composition dissolves a thrombus of a cerebral infarction patient; wherein the administering of the pharmaceutical composition has a low risk of a hemorrhagic side effect; wherein the administering of the pharmaceutical composition reduces the risk of causing hemorrhage in cerebral infarction”, are related to the mechanism of action of the drug, Compound I, in treating cerebral infarction.
According to MPEP 2112.02 (II), “The discovery of a new use for an old structure based on unknown properties of the structure might be patentable to the discoverer as a process of using. In re Hack, 245 F.2d 246, 248, 114 USPQ 161, 163 (CCPA 1957). However, when the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978)”. In the instant case, Nishimura teaches the active step of administering the same composition (TMS-007, i.e., SMTP-7, i.e., Compound I), to the same patient population (a subject having experienced acute ischemic stroke, that would lead to cerebral infarction). Thus, the method of Nishimura, when practiced in treating a human subject with cerebral infarction, would have necessarily produced the same treatment effects. Therefore, the limitations of instant claims 51-53 are anticipated by the disclosure of Nishimura.
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.
Claims 1-2, 11, 15, 17, 37, 42-43, 49 and 51-53 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hasumi et al. (Impact of SMTP Targeting Plasminogen and Soluble Epoxide Hydrolase on Thrombolysis, Inflammation, and Ischemic Stroke, 19 January 2021, hereinafter Hasumi).
Applicant may rely on the exception under 35 U.S.C. 102(b)(1)(A) to overcome this rejection under 35 U.S.C. 102(a)(1) by a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application, and is therefore not prior art under 35 U.S.C. 102(a)(1).
Regarding instant claims 1-2, 11 and 49, Hasumi teaches Stachybotrys microspora triprenyl phenol (SMTP) is a large family of small molecules derived from the fungus S. microspore (Abstract). Hasumi teaches SMTP congeners with both thrombolytic and anti-inflammatory actions plays a key role in the treatment of ischemic stroke in several models of rodents and monkeys (Abstract; Pg. 2, continued paragraph). Hasumi teaches the structure of a key SMTP congener, SMTP-7 (Figure 1).
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Hasumi teaches a potent SMTP congener, TMS-007, administered to human patients with acute ischemic stroke at a dose of 1, 3, and 6 mg/kg as an intravenous infusion (i.e., a pharmaceutical composition) in a randomized, placebo-controlled, double-blind, dose-escalation, parallel group phase 2 clinical study (Pg. 15, first full paragraph). Para. [0008] and Para. [0063] of the instant specification evidences TMS-007 to be a sodium salt preparation of SMTP-7, i.e., Compound I of the instant claims. Hasumi teaches SMTP serves as a drug that promotes recanalization (through enhancement of physiological fibrinolysis) while suppressing hemorrhagic transformation (through anti-inflammatory/antioxidative mechanisms) in ischemic stroke (Pg. 14, first full paragraph). Hasumi teaches the active step of administering a pharmaceutical composition of the same drug (Compound 1) to the same patient population (a subject who has experienced an ischemic stroke, that leads to cerebral infarction). Therefore, practicing the method of Hasumi would result in treating cerebral infarction that ensues following ischemic stroke by restoring blood flow to the brain. Therefore, the disclosure of Hasumi anticipates the limitations of instant claims 1-2, 11 and 49.
Regarding instant claims 15 and 17, Hasumi anticipates the method of treating cerebral infarction in a human as in instant claim 1. Hasumi teaches the patients include cardioembolic and atherothrombotic stroke and lacuna infarction patients who were ineligible for t-PA therapy or endovascular thrombectomy. Therefore, Hasumi anticipates the limitations of instant claims 15 and 17.
Regarding instant claims 42-43 and 51-53, Hasumi anticipates the method of treating cerebral infarction in a human as in instant claim 1. Here, the limitations with respect to “wherein the administering of the pharmaceutical composition improves a life of independence after cerebral infarction, wherein an index of the improvement of a life of independence is outcome of mRS (modified Rankin Scale) of 0-1 on Day 90 after administration; wherein the administering of the pharmaceutical composition improves a life of independence after cerebral infarction, wherein an index of the improvement of a life of independence is outcome of mRS (modified Rankin Scale) of 0-2 on Day 90 after administration; wherein the administering of the pharmaceutical composition dissolves a thrombus of a cerebral infarction patient; wherein the administering of the pharmaceutical composition has a low risk of a hemorrhagic side effect; wherein the administering of the pharmaceutical composition reduces the risk of causing hemorrhage in cerebral infarction”, are related to the mechanism of action of the drug, Compound I, in treating cerebral infarction.
According to MPEP 2112.02 (II), “The discovery of a new use for an old structure based on unknown properties of the structure might be patentable to the discoverer as a process of using. In re Hack, 245 F.2d 246, 248, 114 USPQ 161, 163 (CCPA 1957). However, when the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978)”. In the instant case, the method of Hasumi, when practiced in treating a human subject with cerebral infarction, would have necessarily produced the same treatment effects. Therefore, the limitations of instant claims 41-42 and 51-53 are anticipated by the disclosure of Hasumi.
Regarding instant independent claim 37, Hasumi anticipates the method of treating a human subject with cerebral infarction, comprising administering to the human subject in need thereof a pharmaceutical composition comprising Compound I having the structure of formula (I) or a salt thereof, as discussed above for claim 1. Hasumi teaches SMTP serves as a drug that promotes recanalization (through enhancement of physiological fibrinolysis) while suppressing hemorrhagic transformation (through anti-inflammatory/antioxidative mechanisms) in ischemic stroke (Pg. 14, first full paragraph).
Alternatively, the limitation with respect to “wherein the administering of the pharmaceutical composition recanalizes occluded vessel in cerebral infarction”, is related to the mechanism of action of the drug, Compound I, in treating cerebral infarction. Hasumi teaches the active step of administering a pharmaceutical composition of the same drug (Compound 1) to the same patient population (a subject who has experienced a ischemic stroke, that leads to cerebral infarction). The method of Hasumi, when practiced in treating a human subject with cerebral infarction, would have necessarily produced the same treatment effects. Therefore, the limitations of instant claim 37 are anticipated by the disclosure of Hasumi. See MPEP 2112.02 (II), cited above.
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.
Claims 1-2, 7, 11-15, 17, 22, 41-42 and 51-53 are rejected under 35 U.S.C. 103 as being unpatentable over the Honda et al. (EP 2452679 A1, 16 May 2012, hereinafter Honda, in the IDS).
Regarding instant claim 1 and 49, Honda teaches a method of treatment of ischemic damage including administration of a drug containing a triprenyl phenol compound according to the present invention to a patient 3 or more hours after the onset of a symptom, especially for the treatment of cerebral infraction (Para. [0081]). Honda teaches the subject can be a human (Para. [0076]). Honda teaches a single effective dose for an adult of the triprenyl phenol compound to preferably be 0.1 to 30 mg/kg (Para. [0068]). Honda exemplifies the treatment of cerebral infarction in various animal models comprising administering an exemplary triprenyl phenol compound, SMTP-7 (Paras. [0085]-[00173]). SMTP-7 is taught to be a cryoprotective agent for the treatment of ischemic damage having the following structure (Paras. [0008]-[0010]; Paras. [0060]-[0061], Table 5).
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Honda teaches the triprenyl phenol compounds to have plasminogen activation activity which allows for thrombolysis, as well as cryoprotective effect for inhibiting dysfunction caused by ischemia (Paras. [0006]-[0007]; Para. [0017]). SMTP-7 is Compound I of instant claim 1 as evidenced by Para. [0008] of the instant specification. Honda teaches a test dose of 10 mg/kg of SMTP-7 administered intravenously as a bolus over 5 sec followed by continuous administration over 30 min in a crab-eating monkey cerebral infarction model (Paras. [0154]-[0173]). Honda teaches the administration of SMTP-7 (10 mg/kg) resulted in significant reduction in infraction size in the crab-eating monkey model (Paras. [0172]-[0173]).
According to MPEP 2144.05(II)(A), "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Therefore, it would have taken no more than the relative skills of one of ordinary skill in the art through routine experimentation to have arrived at the claimed human dose of 1 to 6 mg of SMTP-7 (i.e., Compound I), more specifically 1 mg/kg, 3 mg/kg and 6 mg/kg, in the absence of any criticality of the recited doses.
The teachings of Honda render the limitations of instant claims 1-2, 11, 13 prima facie obvious.
Regarding instant claim 7, the teachings of Honda render the method of treating cerebral infarction in a human as in instant claim 1, prima facie obvious. Honda further teaches administration of the agent up to 12 hours after the onset of the symptom (Para. [0069]).
According to MPEP 2144.05(II)(A), "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Therefore, it would have taken no more than the relative skills of one of ordinary skill in the art through routine experimentation to optimize the treatment window, to arrive at the 4.5 to 12 hours after onset of cerebral infarction of the instant claims, with a reasonable expectation of success.
Regarding instant claim 12, the teachings of Honda render the method of treating cerebral infarction in a human as in instant claim 1, prima facie obvious. Honda teaches that there is no particular restriction on the number of administrations, and the use by any of one-time administration, multiple administrations, and a continuous administration is acceptable (Para. [0068]). This renders the limitation drawn to once daily administration, prima facie obvious.
Regarding instant claim 14, the teachings of Honda render the method of treating cerebral infarction in a human as in instant claim 1, prima facie obvious. Honda teaches SMTP-7 administered intravenously as a bolus over 5 sec followed by continuous administration over 30 min in a crab-eating monkey cerebral infarction model. Honda teaches rapid intravenous injection for 10% of a single dose, and a drip infusion over 30 min to 1 hour for 90% thereof (Para. [0070]). Therefore, it would have taken no more than the relative skills of one of ordinary skill in the art through routine experimentation to have optimized the intravenous administration schedule to arrive at the schedule of the instant claims with a reasonable expectation of success. See MPEP 2144.05(II)(A) cited above.
Regarding instant claim 15, the teachings of Honda render the method of treating cerebral infarction in a human as in instant claim 1, prima facie obvious. Honda teaches in the case of cerebral infarction, it is effectual to use a drug containing a triprenyl phenol compound according to the present invention for a patient to whom alteplase cannot be administered because 3 or more hours have passed since the onset of a symptom (Para. [0081]; Paras. [0074]-[0075]). This renders the limitations of claim 15 prima facie obvious.
Regarding instant claim 17, the teachings of Honda render the method of treating cerebral infarction in a human as in instant claim 1, prima facie obvious. Honda teaches the cryoprotective agent is effective in treating cerebral infarction associated with cerebral thrombosis, cerebral embolism pathologies (i.e., pathologies causing atherothombotic/embolic cerebral infarction) (Para. [0024]). This renders the limitations of claim 17 prima facie obvious.
Regarding instant claims 41-42 and 51-53, the teachings of Honda render the method of treating cerebral infarction in a human as in instant claim 1, prima facie obvious. Here, the limitations with respect to “wherein the administering of the pharmaceutical composition improves a life of independence after cerebral infarction, wherein an index of the improvement of a life of independence is outcome of mRS (modified Rankin Scale) of 0-1 on Day 90 after administration; wherein the administering of the pharmaceutical composition improves a life of independence after cerebral infarction, wherein an index of the improvement of a life of independence is outcome of mRS (modified Rankin Scale) of 0-2 on Day 90 after administration; wherein the administering of the pharmaceutical composition dissolves a thrombus of a cerebral infarction patient; wherein the administering of the pharmaceutical composition has a low risk of a hemorrhagic side effect; wherein the administering of the pharmaceutical composition reduces the risk of causing hemorrhage in cerebral infarction”, are related to the mechanism of action of the drug, Compound I, in treating cerebral infarction. Honda teaches the active step of administering a pharmaceutical composition of the same drug (Compound 1) to the same patient population (a subject with cerebral infarction). Therefore, the method of Honda, when practiced in treating a human subject with cerebral infarction, would have necessarily produced the same treatment effects. Therefore, the limitations of instant claims 41-42 and 51-53 are rendered obvious by the teachings of Honda.
Regarding instant claim 22, the teachings of Honda are set forth in the anticipation rejection above and incorporated herein by reference. Honda anticipates the method of instant claim 20.
Honda do not explicitly teach administering the pharmaceutical composition to the human subject 4.5 to 12 hours after the onset of cerebral infarction.
According to MPEP 2144.05(II)(A), "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Therefore, it would have taken no more than the relative skills of one of ordinary skill in the art through routine experimentation to optimize the treatment window, to arrive at the 4.5 to 12 hours after onset of cerebral infarction of the instant claims, with a reasonable expectation of success.
Claims 46-47 are rejected under 35 U.S.C. 103 as being unpatentable over the Honda et al. (EP 2452679 A1, 16 May 2012, hereinafter Honda, in the IDS) as applied to claims 1-2, 7, 11-15, 17, 22, 41-42 and 51-53 above, in view of Koyanagi et al. (Mechanism of the action of SMTP-7, a novel small-molecule modulator of plasminogen activation, 2014, hereinafter Koyanagi).
The teachings of Honda are set forth in the obviousness rejection above and incorporated herein by reference.
Regarding instant claims 46-47, the teachings of Honda render the method of treating cerebral infarction in a human as in instant claim 1, prima facie obvious. Honda teaches the formulation of cryoprotective agent can include any kind of additives (Para. [0067]). Honda do not explicitly teach a basic additive or amphipathic additive as recited in instant claim 47.
Koyanagi teaches SMPT-7 that has excellent therapeutic activities against thrombotic stroke in several rodent models requires a cofactor with a long-chain alkyl or alkenyl group to enhance plasminogen activation (Abstract). Koyanagi teaches an exemplary composition of SMTP-7 with the surfactant Tween 80 (polyoxyethylene sorbitan monooleate) wherein Tween 80 acts as a cofactor for the plasminogen activation action of SMPT-7 (Pg. 318, first column, first paragraph, Fig. 1). Tween 80 is an amphipathic additive.
Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. MPEP 2144.07. Koyanagi teaches Tween 80, an amphipathic additive, as a cofactor that enhances plasminogen activation of SMTP-7. Accordingly, it would have been obvious to one of ordinary skill in the art to have incorporated an amphipathic additive into the composition of SMTP-7, with a reasonable expectation of success. The motivation being to enhance plasminogen activation by SMTP-7.
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-2, 7, 11-15, 17, 20-22, 37-38, 41-42, 46-47, 49 and 51-54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-8, 10-14 and 16-26 of co-pending Application No 18/287,489 in view of Honda et al. (EP 2452679 A1, 16 May 2012, hereinafter Honda, in the IDS).
Although the claims at issue are not identical, they are not patentably distinct from each other because both set of claims are drawn to a method of treating a subject with cerebral infarction comprising administering a composition comprising the same active compound, a compound represented by formula (I) (SMTP-7), and either or both of a basic additive or amphipathic additive.
The instant claims are drawn to a method of treating a human subject with cerebral infarction, comprising administering to the human subject in need thereof a pharmaceutical composition comprising Compound I having the structure of formula (I) (i.e., SMTP-7) or a salt thereof at a dose of 1 to 6 mg/kg as of said Compound I and other embodiments.
The claims of the reference ‘489 application are drawn to a method for preventing or treating an ischemic disorder in a subject in need thereof, wherein the method comprises administering a therapeutically effective amount of a the pharmaceutical composition according to claim 1 to the subject, wherein the pharmaceutical composition comprises a compound represented by formula (1) (i.e., SMTP-7).
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Claims 10-12 of the reference ‘489 application anticipates treating cerebral infraction as in instant claim 1. Claim 13 of the reference ‘489 application anticipates treating acute ischemic stroke as in instant claim 49. Claim 16 anticipates the intravenous administration as in instant claim 11. Claims 3-8 and 18-19 of the reference ‘489 application anticipates the basic and amphipathic additives as in instant claims 46-47. Claim 20 of the reference ‘489 application anticipates the window of administration of the active agent after the onset of cerebral infarction as in instant claims 7 and 20-22. Claims 21-24 of the reference ‘489 application anticipates the patient population as in instant claims 15, 38 and 54.
The reference ‘489 application does not teach the specific dosages of SMTP-7, the administration schedule and the intended treatment effects as in instant claims 41-42 and 51-53.
Honda teaches a single effective dose for an adult of the triprenyl phenol compound to preferably be 0.1 to 30 mg/kg (Para. [0068]). Honda exemplifies the treatment of cerebral infarction in various animal models comprising administering an exemplary triprenyl phenol compound, SMTP-7 (Paras. [0085]-[00173]). Honda teaches a test dose of 10 mg/kg of SMTP-7 administered intravenously as a bolus over 5 sec followed by continuous administration over 30 min in a crab-eating monkey cerebral infarction model (Paras. [0154]-[0173]). Honda teaches the administration of SMTP-7 (10 mg/kg) resulted in significant reduction in infraction size in the crab-eating monkey model (Paras. [0172]-[0173]).
According to MPEP 2144.05(II)(A), "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Therefore, it would have taken no more than the relative skills of one of ordinary skill in the art through routine experimentation to have arrived at the claimed human dose of 1 to 6 mg of SMTP-7, more specifically 1 mg/kg, 3 mg/kg and 6 mg/kg, in the absence of any criticality of the recited doses and the claimed administration schedule.
Regarding the intended treatment effects as in instant claims 41-42 and 51-53, performing the active step of administering a pharmaceutical composition of SMTP-7 to a subject with cerebral infarction, as taught by the reference ‘489 application, would have necessarily resulted in the intended treatment effects.
Therefore, claims 1, 3-8, 10-14 and 16-26 of the reference ‘489 application in view of Honda renders the instant compounds of claims 1-2, 7, 11-15, 17, 20-22, 37-38, 41-42, 46-47, 49 and 51-54 prima facie obvious.
The instant claims 1-2, 7, 11-15, 17, 20-22, 37-38, 41-42, 46-47, 49 and 51-54 and claims 1, 3-8, 10-14 and 16-26 of co-pending Application No 18/287,489 are therefore not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1-2, 7, 11-15, 17, 20-22, 37-38, 41-42, 46-47, 49 and 51-54 are rejected.
No claims are allowed.
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/PADMAJA S RAO/Examiner, Art Unit 1627