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
Response to Amendment
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 12/08/2025 has been entered.
Newly amended Claims 23-38 are pending in the application and examined herein.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied and constitute the complete set presently being applied to the instant application.
Response to Applicant’s Arguments
Applicant argues the NSDP rejections issued over applications 17607449 and 17607464, which have since matured into patents no. 12365665 and 12459917, should be withdrawn as a result of the terminal disclaimers filed against both applications. This argument is persuasive and the rejections over both are withdrawn.
Regarding the extant NSDP rejections, applicant traverses them for the following reasons. Hawley fails to teach the same embodiments as taught in Zhao while Zhao fails to teach the P2X3 inhibitors for treating cough or resistant cough. Second, Applicant argues Zhao teaches against selecting Compounds 2 or 66 because they are not the most potent compounds. Third, Hawley “teaches away” from using oxygen or carbon-linked compounds over sulfur-linked analogs due to increased potency and P2X3 receptor selectivity over P2X2/3. Lastly, applicant suggests the claimed compounds exhibit unexpected therapeutic efficacy at the clinical stage. All Applicant’s arguments are fully considered but not persuasive for the following reasons.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In response to applicant's arguments against the Zhao and Hawley individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Zhao teaches P2X3 inhibitor compounds while Hawley teaches a broad genus encompassing the compounds taught in Zhao to treat cough, including resistant cough.
Regarding the discussion of Compounds 2 and 66 as not being the most optimal or potent compounds taught by Zhao, the Federal Circuit in Eisai makes it clear that from the perspective of the law of obviousness, any known compound might possibly serve as a lead compound: "Obviousness based on structural similarity thus can be proved by identification of some motivation that would have led one of ordinary skill in the art to select and then modify a known compound (i.e. a lead compound) in a particular way to achieve the claimed compound." Eisai, 533 F.3d at 1357, 87 USPQ2d at 1455. There must be some reason for starting with that particular lead compound other than the mere fact that the "lead compound" exists. (See MPEP 2143 I B Example 9.) The particular reasoning for selecting the Zhao inhibitors is that Zhao teaches the compounds as P2X3 inhibitors while Hawley teaches a genus of inhibitors encompassing the compounds of Zhao for the treatment of P2X3 associated disorders like resistant cough. Therefore, the cited Zhao compounds are appropriately selected in the below rejections for their inhibitory activity.
Hawley does not in fact “teach away” from selecting the claimed compounds by virtue of their being o-linked rather than s-linked. Hawley encompasses o-linked compounds in Formula I and teaches them for use in P2X3 or P2X2/3-associated disorders (Page 3). A compound does not have to be the “most preferred” or “most potent” compound to be obvious. See In re Fulton, 391 F.3d 1195, 1200 (Fed. Cir. 2004) (a conclusion of obviousness does not require “something in the prior art as a whole to suggest that the combination is the most desirable combination available”). See also In re Susi, 440 F.2d 442, 446 n.3 (CCPA 1971) (Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or non-preferred embodiments.). In re Mouttet, 686 F.3d 1322, 1334 (Fed. Cir. 2012) (noting that “just because better alternatives exist in the prior art does not mean that an inferior combination is inapt for obviousness purposes”), In re Fulton, 391 F.3d 1195, 1200 (Fed. Cir. 2004) (stating that “finding that the prior art as a whole suggests the desirability of a particular combination need not be supported by a finding that the prior art suggests that the combination claimed by the patent applicant is the preferred, or most desirable, combination”), Altana Pharma AG v. Teva Pharm. USA, Inc., 566 F.3d 999, 1008 (Fed. Cir. 2009) See also Merck & Co., Inc. v. Biocraft Laboratories, Inc., 874 F.2d 804, 807 (Fed. Cir. 1989) (quoting In re Lamberti, 545 F.2d 747, 750 (CCPA 1976)) (“[I]n a section 103 inquiry, ‘the fact that a specific [embodiment] is taught to be preferred is not controlling, since all disclosures of the prior art, including unpreferred embodiments, must be considered.’”). See also In re Mills, 470 F.2d 649,651 (CCPA 1972) ("All the disclosures in a reference must be evaluated, including nonpreferred embodiments, and a reference is not limited to the disclosure of specific working examples.").
Regarding Zhao and Hawley lacking clinical results, both use assay data to model therapeutic efficacy as is standard in the art. One of skill in the art would expect therapeutic effects to result from compounds which exhibit success in in vitro assays because the goal of an assay is to model in vivo therapeutic activity. Applicant also describes Compounds 2 and 66 as having “unexpectedly…superior antitussive effect” as compared to the clinical control compound. This argument however cannot be evaluated on its merits because applicant only offers a comparison between the vehicle control and each antitussive compound individually. No statistical comparison between pharmaceutical compounds is offered to evaluate applicant’s arguments, nor is an evidentiary declaration filed to demonstrate or support applicants conclusion of unexpected results.
For the above reasons, the following NSDP rejections are issued and amended appropriately below.
Double Patenting
1. Claims 23-38 are provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable over Claims 1-12 and 14-15 of copending Application No. 19273198 (hereinafter referred to as Zhao) in view of Hawley (WO2017165255, published 9/28/2017).
Although the claims at issue are not identical, they are not patentably distinct from each other because both applications are directed to the treatment of P2X3 mediated conditions like COPD comprising administering elected Compound 66,
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,. Regarding the claims directed to compositions of matter, In AbbVie Inc. v. Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 112 USPQ2d 1001 (Fed. Cir. 2014), the court explained that it is also proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a nonstatutory double patenting context. See Sun Pharm. Indus., Ltd. v. Eli Lilly & Co., 611 F.3d 1381, 95 USPQ2d 1797 (Fed. Cir. 2010). See MPEP 804 (II) (B) (1).
Zhao fails to teach P2X3 antagonists for use in the treatment of treatment-resistant cough.
Hawley teaches compounds of Formula 1:
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, which share a diaminopyrimidine core with Zhao and are also useful as P2X3 antagonists (Abstract). Hawley teaches P2X3 antagonists as useful for the treatment of treatment-resistant cough as elected by applicant and listed in Claim 22 (Page 6, Para 1; Page 8, Para 5; Page 19, Last Para).
One of ordinary skill in the art seeking to treat treatment-resistant cough with a P2X3 antagonist as taught by Hawley would find it obvious to use Compound 66 of Zhao because both references teach their respective diaminopyrimidine compounds as P2X3 antagonists. The same artisan would expect successful treatment of the cough because Zhao teaches Compound 66 as an effective inhibitor of P2X3 and Hawley teaches P2X3 inhibitors are useful for the treatment of said disease.
Hawley further teaches P2X3 antagonists as useful for the treatment of treatment-resistant cough as elected by applicant and listed in Claim 22 (Page 6, Para 1; Page 8, Para 5; Page 19, Last Para). Regarding Claims 15-16 and 20-21, the antagonists can be administered orally as tablets or other forms preferably in an amount of 1-30mg/day, which is roughly 14ug-500ug/kg body weight for a 70kg patient (Page 52). Regarding Claims 25-31 and 33-37, the doses may be adjusted and optimized “depending upon numerous factors such as the severity of the disease to be treated, the age and relative health of the subject, the potency of the compound used, the route and form of administration, the indication towards which the administration is directed, and the preferences and experience of the medical practitioner involved” (Page 52, Para 1). The compound can be administered as a single dose as required by Claim 17 (Page 54, Last Para).
Since both applications teach methods of administering the same compounds to treat P2X3-mediated diseases, including COPD, the examiner maintains that the aforementioned claims of the instant application are substantially overlapping in scope as discussed hereinabove and are prima facie obvious over the cited claims of Zhao.
This is a provisional nonstatutory double patenting rejection.
NONPROVISIONAL:
1. Claims 23-38 are provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable over Claims 1-6, 8-13, and 15 of US Patent No. 11414444 (hereinafter referred to as Zhao) in view of Hawley (WO2017165255, published 9/28/2017).
Although the claims at issue are not identical, they are not patentably distinct from each other because both applications are directed to elected Compound 66,
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Zhao teaches the compound as a P2X3 and P2X2/3 inhibitor. Regarding these patented claims directed to compositions of matter, In AbbVie Inc. v. Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 112 USPQ2d 1001 (Fed. Cir. 2014), the court explained that it is also proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a nonstatutory double patenting context. See Sun Pharm. Indus., Ltd. v. Eli Lilly & Co., 611 F.3d 1381, 95 USPQ2d 1797 (Fed. Cir. 2010). See MPEP 804 (II) (B) (1).
Zhao fails to teach P2X3 antagonists for use in the treatment of treatment-resistant cough.
Hawley teaches compounds of Formula 1:
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, which share a diaminopyrimidine core with Zhao and are also useful as P2X3 antagonists (Abstract). Hawley teaches P2X3 antagonists as useful for the treatment of treatment-resistant cough as elected by applicant and listed in Claim 22 (Page 6, Para 1; Page 8, Para 5; Page 19, Last Para).
One of ordinary skill in the art seeking to treat treatment-resistant cough with a P2X3 antagonist as taught by Hawley would find it obvious to use Compound 66 of Zhao because both references teach their respective diaminopyrimidine compounds as P2X3 antagonists. The same artisan would expect successful treatment of the cough because Zhao teaches Compound 66 as an effective inhibitor of P2X3 and Hawley teaches P2X3 inhibitors are useful for the treatment of said disease.
Hawley further teaches P2X3 antagonists as useful for the treatment of treatment-resistant cough as elected by applicant and listed in Claim 22 (Page 6, Para 1; Page 8, Para 5; Page 19, Last Para). Regarding Claims 15-16 and 20-21, the antagonists can be administered orally as tablets or other forms preferably in an amount of 1-30mg/day, which is roughly 14ug-500ug/kg body weight for a 70kg patient (Page 52). Regarding Claims 25-31 and 33-37, the doses may be adjusted and optimized “depending upon numerous factors such as the severity of the disease to be treated, the age and relative health of the subject, the potency of the compound used, the route and form of administration, the indication towards which the administration is directed, and the preferences and experience of the medical practitioner involved” (Page 52, Para 1). The compound can be administered as a single dose as required by Claim 17 (Page 54, Last Para).
Since both claim sets teach methods of administering the same compounds to treat P2X3-mediated diseases, the examiner maintains that the aforementioned claims of the instant application are substantially overlapping in scope as discussed hereinabove and are prima facie obvious over the cited claims of Zhao.
2. Claims 23-38 are provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable over Claims 1-7 and 10 of US Patent No. 11919918 (hereinafter referred to as Zhao) in view of Hawley (WO2017165255, published 9/28/2017).
Although the claims at issue are not identical, they are not patentably distinct from each other because both applications are directed to the treatment of P2X3 mediated conditions comprising administering elected Compound 66,
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Zhao fails to teach P2X3 antagonists for use in the treatment of treatment-resistant cough.
Hawley teaches compounds of Formula 1:
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, which share a diaminopyrimidine core with Zhao and are also useful as P2X3 antagonists (Abstract). Hawley teaches P2X3 antagonists as useful for the treatment of treatment-resistant cough as elected by applicant and listed in Claim 22 (Page 6, Para 1; Page 8, Para 5; Page 19, Last Para).
One of ordinary skill in the art seeking to treat treatment-resistant cough with a P2X3 antagonist as taught by Hawley would find it obvious to use Compound 66 of Zhao because both references teach their respective diaminopyrimidine compounds as P2X3 antagonists. The same artisan would expect successful treatment of the cough because Zhao teaches Compound 66 as an effective inhibitor of P2X3 and Hawley teaches P2X3 inhibitors are useful for the treatment of said disease.
Hawley further teaches P2X3 antagonists as useful for the treatment of treatment-resistant cough as elected by applicant and listed in Claim 22 (Page 6, Para 1; Page 8, Para 5; Page 19, Last Para). Regarding Claims 15-16 and 20-21, the antagonists can be administered orally as tablets or other forms preferably in an amount of 1-30mg/day, which is roughly 14ug-500ug/kg body weight for a 70kg patient (Page 52). Regarding Claims 25-31 and 33-37, the doses may be adjusted and optimized “depending upon numerous factors such as the severity of the disease to be treated, the age and relative health of the subject, the potency of the compound used, the route and form of administration, the indication towards which the administration is directed, and the preferences and experience of the medical practitioner involved” (Page 52, Para 1). The compound can be administered as a single dose as required by Claim 17 (Page 54, Last Para).
Since both claim sets teach methods of administering the same compounds to treat P2X3-mediated diseases, the examiner maintains that the aforementioned claims of the instant application are substantially overlapping in scope as discussed hereinabove and are prima facie obvious over the cited claims of Zhao.
3. Claims 23-38 are provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable over Claims 1-17 of copending Application No. 12509479 (hereinafter referred to as Zhao) in view of Hawley (WO2017165255, published 9/28/2017).
Although the claims at issue are not identical, they are not patentably distinct from each other because both applications are directed to the treatment of P2X3 mediated conditions comprising administering elected Compound 66,
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, and
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. Regarding the claims directed to compositions of matter, In AbbVie Inc. v. Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 112 USPQ2d 1001 (Fed. Cir. 2014), the court explained that it is also proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a nonstatutory double patenting context. See Sun Pharm. Indus., Ltd. v. Eli Lilly & Co., 611 F.3d 1381, 95 USPQ2d 1797 (Fed. Cir. 2010). See MPEP 804 (II) (B) (1).
Zhao fails to teach P2X3 antagonists for use in the treatment of treatment-resistant cough.
Hawley teaches compounds of Formula 1:
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, which share a diaminopyrimidine core with Zhao and are also useful as P2X3 antagonists (Abstract). Hawley teaches P2X3 antagonists as useful for the treatment of treatment-resistant cough as elected by applicant and listed in Claim 22 (Page 6, Para 1; Page 8, Para 5; Page 19, Last Para).
One of ordinary skill in the art seeking to treat treatment-resistant cough with a P2X3 antagonist as taught by Hawley would find it obvious to use Compound 66 of Zhao because both references teach their respective diaminopyrimidine compounds as P2X3 antagonists. The same artisan would expect successful treatment of the cough because Zhao teaches Compound 66 as an effective inhibitor of P2X3 and Hawley teaches P2X3 inhibitors are useful for the treatment of said disease.
Hawley further teaches P2X3 antagonists as useful for the treatment of treatment-resistant cough as elected by applicant and listed in Claim 22 (Page 6, Para 1; Page 8, Para 5; Page 19, Last Para). Regarding Claims 15-16 and 20-21, the antagonists can be administered orally as tablets or other forms preferably in an amount of 1-30mg/day, which is roughly 14ug-500ug/kg body weight for a 70kg patient (Page 52). Regarding Claims 25-31 and 33-37, the doses may be adjusted and optimized “depending upon numerous factors such as the severity of the disease to be treated, the age and relative health of the subject, the potency of the compound used, the route and form of administration, the indication towards which the administration is directed, and the preferences and experience of the medical practitioner involved” (Page 52, Para 1). The compound can be administered as a single dose as required by Claim 17 (Page 54, Last Para).
Since both applications teach methods of administering the same compounds to treat P2X3-mediated diseases, the examiner maintains that the aforementioned claims of the instant application are substantially overlapping in scope as discussed hereinabove and are prima facie obvious over the cited claims of Zhao.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowable.
Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Richard G. Peckham whose telephone number is (703)756-4621. The examiner can normally be reached 7:30am - 4:30pm.
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/RICHARD GRANT PECKHAM/Examiner, Art Unit 1627
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627