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
Status of 17/441,484
Claims 1, 3-4, and 19-22 are currently pending.
Priority
Instant application 17/441,484, filed 9/21/2021, claims priority as follows:
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Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
All references from the IDS received September 21st, 2021 have been considered unless marked with a strikethrough.
Response to Amendments/Arguments
The amendment filed 10/27/2025 has been entered. Applicant has amended claims 1, 3-4, and 22. No claims have been added or cancelled.
In the Non-Final Rejection dated 7/31/2025, the specification was objected to for containing browser-executable code. In response, Applicant has deleted the browser-executable code to overcome the objection. Thus, the objection is withdrawn.
Claims 1 and 19-22 were rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) in the Non-Final Rejection dated 7/31/2025. In response, Applicant argues the evidentiary reference Levine (Levine, J. A. et. al. Sci. Rep. 2021, 11, 430) is not prior art, and thus can’t be used, and that the rejection is improper.
Levine is able to be used as an evidentiary reference, not as prior art, because it includes facts such as the characteristics and properties of a material as stated in MPEP § 2124. In this case, Levine includes facts of the characteristics and properties of the chemical compound TM5614.
Additionally, Applicant argues that the Office’s reasoning based on In re Spada is not reasonable because all of Spada’s claims are composition claims, and the issue of Spada is not whether Spada may have discovered the new use of a known composition. The Examiner acknowledges this, but reiterates that the argument at present is inherency, which Spada does include even if not recited verbatim. Further Applicant argues that claim 1 is clearly directed to a new use of a composition and that there is no prior art that teaches the use of PAI-1 to reduce plasma, LDL, HDL, and cholesterol or methods thereof. The arguments have been considered, but are not persuasive because Applicant has not provided evidence to overcome the fact that the reduction of plasma LDL, HDL, and cholesterol occurred after oral administration of TM5614 in the patient population of Renascience Co., LTD. (US 2016/0158188, herein after “Renascience”). MPEP § 2112 further states:
“Where applicant claims a composition in terms of a function, property or characteristic and the composition of the prior art is the same as that of the claim but the function is not explicitly disclosed by the reference, the examiner may make a rejection under both 35 U.S.C. 102 and 103. "There is nothing inconsistent in concurrent rejections for obviousness under 35 U.S.C. 103 and for anticipation under 35 U.S.C. 102." In re Best, 562 F.2d 1252, 1255 n.4, 195 USPQ 430, 433 n.4 (CCPA 1977). This same rationale should also apply to product, apparatus, and process claims claimed in terms of function, property or characteristic. Therefore, a 35 U.S.C. 102 and 103 rejection is appropriate for these types of claims as well as for composition claims.”
Which applies in this case because while Renascience does not explicitly disclose all of the functions, properties, or characteristics of TM5614, it does disclose a method of treatment by orally administering TM5614 to the same patient population as the instant disclosure, which in turn must have reduced the LDL, HDL, and cholesterol in the patient population as a result of PAI-1 inhibition. TM5614 of Renascience and of the instant disclosure are identical chemical composition and thus cannot have mutually exclusive properties. In order to overcome the rejection, Applicant must provide evidence that the prior art products do not necessarily possess the characteristics of the claimed product according to MPEP § 2112.01(I). Thus, the rejection is maintained.
Claims 3 and 4 were rejected under 35 U.S.C. 103 in the Non-Final dated 7/31/2025. In response, Applicant presented the above arguments and also argues that the reference Lawrence does not remedy the deficiencies of Renascience. Applicant’s arguments have been considered, but are not persuasive for the same reasons as stated above. The rejection is therefore maintained.
In the Non-Final Rejection dated 7/31/2025, claims 1 and 19-20 were rejected on the grounds of nonstatutory double patenting. Applicant did not address this rejection in the response filed 10/27/2025 and thus, the rejection is maintained.
MAINTAINED REJECTIONS
Election/Restriction
Applicants’ election of Group I, claims 1-6, without traverse in the reply filed 9/5/2024, is acknowledged. Over the course of prosecution, claims 2 and 5-18 were cancelled, and claims 19-22 have been added and are considered to be part of Group I.
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 (i.e., changing from AIA to pre-AIA ) 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1 and 19-22 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Renascience Co., LTD. (US 2016/0158188, herein after “Renascience”) as evidenced by Levine (Levine, J. A. et. al. Sci. Rep. 2021, 11, 430).
Regarding claims 1 and 20, the reference Renascience discloses the sodium salt TM5614, sodium 5-chloro-2-({[3-( quinolin-8-yl)phenyl]carbonyl}amino)benzoate, as example 68 in Table 2 (page 30) with an inhibitory effect on PAI-1 at 10 μM and 2.5 μM. The authors note example 68 is also referred to as compound d (page 65, para [1049]). Further, Renascience discloses a method of treating mice xenografted with ovarian cancer cells by orally administering compound d to the subject (page 77, para [1241]).
Evidentiary reference Levine acknowledges that mechanism of PAI-1 inhibition and reduction of plasma LDL, HDL, and cholesterol had not been completely elucidated prior to publication. Specifically, the authors state, “no studies have described or investigated a mechanistic link between PAI-1 and dyslipidemia”, and, “this newly discovered mechanistic relationship allows for the identification of PAI-1 as a singular factor that directly contributes to each of the clinical components of metabolic syndrome” (page 1, para 3). Levine additionally discloses that inhibition of PAI-1 with TM5614 lowers plasma LDL, HDL, and cholesterol (page 2, para 3 and page 5, Fig. 3C). Thus, though the reference Renascience doesn’t explicitly disclose the reduction of plasma LDL, HDL, and cholesterol as a result of PAI-1 inhibition, Levine discloses the elucidation of the mechanism at a later date. While silent in Renascience, the orally administered TM5614 to the same patient population as the instant disclosure must have reduced the plasma LDL, HDL, and cholesterol in the patients as products of identical chemical composition cannot have mutually exclusive properties. In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties Applicant discloses and/or claims are necessarily present. See MPEP § 2112.
With respect to claim 19, it is known to one of ordinary skill in fundamental acid/base chemistry that there is an equilibrium between the sodium salt and the free acid upon oral administration of TM5614 into the aqueous environment of the patient. Thus, though not explicitly defined, the free acid of TM5614 is present in the teachings of Renascience.
With respect to claims 21 and 22, the reference Renascience discloses a preferable dosage of 0.03 to 30 mg/kg/day, which satisfies these limitations (page 60, para [0976]).
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 3 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Renascience Co., LTD. (US 2016/0158188, herein after “Renascience”), as evidenced by Levine (Levine, J. A. et. al. Sci. Rep. 2021, 11, 430), and further in view of Lawrence (US 2015/0315178 A1, cited in the IDS of 9/21/2021).
Determining the scope and contents of the prior art
The references Renascience as evidenced by Levine teach as disclosed above, and at least those teachings are incorporated herein.
Lawrence teaches combination therapies of a PAI-1 inhibitor and at least one other therapeutic agent (second therapeutic agent) (page 41, para [0176]), and specifically designates the other therapeutic agents as drugs used to manage cardiovascular disease including, but not limited to, cholesterol lowering drugs, such as statins, anti-inflammatories, and ACE inhibitors. Lawrence explicitly defines the limitation of “statins”, and the limitation of PCSK9 inhibitors is satisfied by Lawrence’s teaching of “cholesterol lowering drugs”. The instant specification defines PCSK9 inhibitors as cholesterol lowering drugs by, “the result of the inhibition or decrease of PCSK9 is a decrease the fasting plasma LDL in a subject” (para [0039]), and that PCSK9 is, “a regulator of plasma cholesterol levels” (para [0007]).
Ascertaining the differences between the prior art and the claims at issue
Renascience, as evidenced by Levine, fails to teach co-administration of the PAI-1 inhibitor TM5614 with a statin or a PCSK9 inhibitor, whereas Lawrence fails to teach TM5614 as the PAI-1 inhibitor and the method limitations of the instant claims.
Resolving the level of ordinary skill in the pertinent art
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of methods of treatment with PAI-1 inhibitors. An artisan possess the technical knowledge necessary to make adjustments to the methods of treatment with PAI-1 inhibitors to enhance their effectiveness. Said artisan has also reviewed the problems in the art as regards to methods of treatment with PAI-1 inhibitors and understands the solutions that are widely known in the art.
Considering objective evidence present in the application indicating obviousness or nonobviousness
Applying KSR Prong (A), it would have been prima facie obvious to one of ordinary skill in the art to combine the teachings of Renascience, as evidenced by Levine, and Lawrence to arrive at methods of treatment with PAI-1 inhibitors co-administered with a statin or PCSK9 inhibitor, because combinations of PAI-1 inhibitors and statins or PCSK9 are known in the art. One would be motivated before the effective filing date to use combinations of the drugs to expand the scope of combination therapies able to treat diseases, particularly the reduction of plasma LDL, HDL, and cholesterol in a subject. Since this modification of the prior art represents nothing more than “the predictable use of prior art elements according to their established functions”, a prima facie case of obviousness exists.
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 and 19-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7, 9, and 11 of U.S. Patent No. 8,785,473 (herein after the ‘473 patent) as evidenced by Levine (Levine, J. A. et. al. Sci. Rep. 2021, 11, 430). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘473 patent recite compounds of Formula (I) of which TM5614 maps to. Claim 1 of the ‘473 patent recites a compound of Formula (I):
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Which maps to TM5614 when R1 is halogen, R2 is hydrogen, B is COOR9, where R9 is a hydrogen or a group converted to a hydrogen in vivo, X is vinylene (-CH=CH-), L is a bond, A is
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, R3 is H, R4 is H, q is 1, T is a single bond, and D is heteroaryl, and claims 7, 9, and 11 further limit the compound of claim 1. Levine teaches as disclosed above, and at least those teachings are incorporated herein. The utility disclosed in the instant specification provides further support for a nonstatutory double patenting rejection. See MPEP § 804(I)(B)(1) and Sun Pharm. Indus., Ltd. v. Eli Lilly & Co., 611 F.3d 1381, 95 USPQ2d 1797 (Fed. Cir. 2010). Thus, though not explicitly stated, the orally administered TM5614 to the same patient population as the instant disclosure must have reduced the plasma LDL, HDL, and cholesterol in the patients as products of identical chemical composition cannot have mutually exclusive properties.
Claims 1 and 19-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 and 5 of U.S. Patent No. 10,092,537 (herein after the ‘537 patent) as evidenced by Levine (Levine, J. A. et. al. Sci. Rep. 2021, 11, 430). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘537 patent recite methods of treatment in a subject with compounds of Formula (I) of which TM5614 maps to. Claim 1 of the ‘537 patent recites a method of treatment in a patient with a compound of Formula (I):
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Which maps to TM5614 when R1 is hydrogen, R2 is halogen, B is COOR9, where R9 is a hydrogen or a group converted to a hydrogen in vivo, X is vinylene (-CH=CH-), L is a bond, A is
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, R3 is H, R4 is H, q is 1, T is a single bond, and D is a quinolyl, and claims 2-3 and 5 further limit the compound of claim 1. Levine teaches as disclosed above, and at least those teachings are incorporated herein. Thus, though not explicitly stated, the orally administered TM5614 to the same patient population as the instant disclosure must have reduced the plasma LDL, HDL, and cholesterol in the patients as products of identical chemical composition cannot have mutually exclusive properties.
Conclusion
Claims 1, 3-4, and 19-22 are rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kendall Heitmeier whose telephone number is (703)756-1555. The examiner can normally be reached Monday-Friday 8:30AM-5:00PM ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton Brooks can be reached at 571-270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/K.N.H./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621