DETAILED ACTION
Claims 1-10 are currently pending in the instant application.
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 .
Priority
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Information Disclosure Statement
The listing of references in the PCT international search report is not considered to be an information disclosure statement (IDS) complying with 37 CFR 1.98. 37 CFR 1.98(a)(2) requires a legible copy of: (1) each foreign patent; (2) each publication or that portion which caused it to be listed; (3) for each cited pending U.S. application, the application specification including claims, and any drawing of the application, or that portion of the application which caused it to be listed including any claims directed to that portion, unless the cited pending U.S. application is stored in the Image File Wrapper (IFW) system; and (4) all other information, or that portion which caused it to be listed. In addition, each IDS must include a list of all patents, publications, applications, or other information submitted for consideration by the Office (see 37 CFR 1.98(a)(1) and (b)), and MPEP § 609.04(a), subsection I. states, “the list ... must be submitted on a separate paper.” Therefore, the references cited in the international search report have not been considered. Applicant is advised that the date of submission of any item of information in the international search report will be the date of submission of the IDS for purposes of determining compliance with the requirements for the IDS with 37 CFR 1.97, including all timing statement requirements of 37 CFR 1.97(e). See MPEP § 609.05(a).
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-4 and 6-10 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claims 1, 3-4 and 7, the phrase "such as" 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). For claims 1 and 7, in the definition of R2, C1-6 alkyl is recited to be “such as -CH3 and -CH2CH3”. Claims 3 and 4 also state that R2 is selected from the group O-C1-6-alkyl such as -O-CH3, etc. As claims 2, 6 and 8-10 do not fix the issue, they have also been rejected.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (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 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 1-10 are rejected under 35 U.S.C. 103 as being unpatentable over Bouyssou et al (see US Pub No. 2019/0169168 (pub. 06/06/2019 and filed 10/25/2018, hereafter referred to as US ‘168) in view of Berry et al (see WIPO Pub No. WO 2019/161010, pub. 08/22/2019 and filed 02/14/2019) and GU et al (see Eur Respir Rev, 2020, Vol. 26, p. 1-12).
US ‘168 teaches compounds of formula
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and exemplifies compounds such as
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and
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(see Table 1, p. 6-23) which correspond to species found in instant claim 5 (see compounds 6 & 7). Note, these are just a selection of representative species described in US ‘168. US ‘168 teaches that the compounds modulate TRPC6 function and may be used to treat a TRPC6 mediated disorder in a subject and administered as a composition (see paragraphs [0211]- [0212], p. 25). US ‘168 teaches the compounds may be used to treatment diseases such as inflammatory diseases (see paragraph [0948], p. 114). The compositions may contain at least about 5%, more preferable at least about 20% of a compound (see paragraph [0953], p. 114). US ‘168 does not name treating systemic inflammatory response to bacterial or fungal infection as a disease that may be treated.
Berry et al teach TRPC6 inhibitors may be useful to reduce the rate of mortality in sepsis, severe sepsis and septic shock as survival rate in model of system sepsis was significantly improved in TRPC6 deficient mice (see p. 7). Thus, Berry et al teach compounds similar in structure to those of US ‘168, which are also TRPC6 inhibitors, can be used to treat sepsis as well as inflammatory disease (see p. 100). Berry et al do not teach that the inflammatory disease or sepsis occurs in response to a bacterial or fungal infection.
GU et al teaches that sepsis is a complex syndrome that results from infection and defined as a life-threatening organ dysfunction resulting from dysregulated host responses to infection (see introduction, p. 1). GU et al further teach that bacteria have been shown to be the predominant pathogens of sepsis caused by infection and proportions of gram-positive and gram-negative organisms among adult septic patients were both around 40%. Further, respiratory viral infections were underdiagnosed in patients with sepsis or septic shock (see 1st full paragraph, p. 2). Viruses were detected in around one-third of adult patients with sepsis. According to Surviving Sepsis Campaign, intravenous antibiotics within 1 hr after recognition of both sepsis and septic shock is strongly recommended (see second full paragraph, p. 2). GU et al reference Kumar et al (Crit Care Med, 2006 Jun;34(6):1589-96) which teaches that effective antimicrobial administration within the first hour of documented hypotension was associated with increased survival to hospital discharge in adult patients with septic shock (see conclusion) and that onset of hypotension is a critical marker of increased mortality in a murine model of Escherichia coli peritonitis/septic shock. Thus, hypotension is taught to be a marker of septic shock. This reads on claim 6.
Prior to the filing of the instant application, one of ordinary skill in the art following the teachings of US ‘168 would have found it prima facie obvious to utilize said compounds and pharmaceutical compositions comprising said compounds, which are taught to be used in treatment of diseases alleviated by TRPC6 inhibition, including inflammation, to treat a systemic inflammatory response to a bacterial or fungal infection. Berry et al teach that TRPC6 inhibitors useful to reduce the rate of mortality in sepsis, severe sepsis and septic shock. GU et al teach that sepsis is a complex syndrome that results from infection and defined as a life-threatening organ dysfunction resulting from dysregulated host responses to infection and that intravenous antibiotics within 1 hr after recognition of both sepsis and septic shock is strongly recommended. Bacteria have been shown to be the predominant pathogens of sepsis caused by infection and viruses were detected in around one-third of adult patients with sepsis. Thus it would follow that the compounds of US ‘168 taught to be inhibitors of TRPC6, which Berry et al teaches can be used to treat sepsis, would be useful in treating sepsis. As Gu et al teach that bacterial are predominant pathogens of sepsis and viruses were detected in around 1/3 adult patients with sepsis. Thus, it would follow that the compounds of US ‘168 could be used to treat a systemic inflammatory response such as sepsis that occurs in response to a bacterial or fungal infection as bacteria are generally found to be associated with sepsis and intravenous antibiotics within 1 hr after recognition of both sepsis and septic shock is strongly recommended. MPEP 2143 states that it would be obvious to combining prior art elements according to known methods to yield predictable results. At the time of the invention, the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395; B/E Aerospace, Inc. v. C&D Zodiac, Inc., 962 F.3d 1373, 1379, 2020 USPQ2d 10706 (Fed. Cir. 2020).
Regarding the limitations of claims 9-10, US ‘168 teaches compositions may contain at least about 5% of the claimed compound. MPEP 2144.05, Section I teaches that in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). Further, according to MPEP 2144.05, Section II (A), generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[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).
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.
Rejection I
Claims 1-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of U.S. Patent No. 10,800,757 (hereafter referred to as ‘757) in view of Berry et al (see WIPO Pub No. WO 2019/161010, pub. 08/22/2019 and filed 02/14/2019) and GU et al (see Eur Respir Rev, 2020, Vol. 26, p. 1-12).
‘757 is drawn to compounds of formula
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and composition comprising said compounds, such as
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(see 1st compound in claim 1). The compounds of ‘757 correspond to the compounds embraced by methods of use in the instant application. Within ‘757, the compounds are taught to be inhibitors of TRPC6 and used to treatment diseases such as inflammatory diseases. “A claim to a method of using a composition is not patentably distinct from an earlier claim to the identical composition in a patent disclosing the identical use,” extends to any and all such uses disclosed in the specification of the earlier patent. See In Re Pfizer, 518 F.3d at 1363; Geneva, 349 F.3d at 1385-86. In the instant case, Applicant is claiming methods of using compounds that overlap in scope with the compounds found in ‘757.
Berry et al teach TRPC6 inhibitors may be useful to reduce the rate of mortality in sepsis, severe sepsis and septic shock as survival rate in model of system sepsis was significantly improved in TRPC6 deficient mice (see p. 7) and pharmaceutical compositions comprising said compounds contain at least about 5% but more preferably at least about 20 % (see p. 102). GU et al teach that sepsis is a complex syndrome that results from infection and defined as a life-threatening organ dysfunction resulting from dysregulated host responses to infection and that intravenous antibiotics within 1 hr after recognition of both sepsis and septic shock is strongly recommended. Bacteria have been shown to be the predominant pathogens of sepsis caused by infection and viruses were detected in around one-third of adult patients with sepsis. GU et al reference Kumar et al (Crit Care Med, 2006 Jun;34(6):1589-96) which teaches that effective antimicrobial administration within the first hour of documented hypotension was associated with increased survival to hospital discharge in adult patients with septic shock (see conclusion) and that onset of hypotension is a critical marker of increased mortality in a murine model of Escherichia coli peritonitis/septic shock. Thus, hypotension is taught to be a marker of septic shock.
Thus at the time of filing, it would have been obvious to utilize the compounds of ‘757 in view of Berry et al and GU et al to arrive at the methods of the instant claims. The compounds of ‘757 are taught to be inhibitors of TRPC6, which Berry et al teaches can be used to treat sepsis. Gu et al teach that bacterial are predominant pathogens of sepsis and viruses were detected in around 1/3 adult patients with sepsis. Thus, it would follow that the compounds of ‘757 could be used to treat a systemic inflammatory response such as sepsis that occurs in response to a bacterial or fungal infection as these agents are generally found to be associated with sepsis. At the time of the invention, the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395; B/E Aerospace, Inc. v. C&D Zodiac, Inc., 962 F.3d 1373, 1379, 2020 USPQ2d 10706 (Fed. Cir. 2020).
Rejection II
Claims 1-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of U.S. Patent No. 10,889,568, hereafter referred to as ‘568, in view of Berry et al (see WIPO Pub No. WO 2019/161010, pub. 08/22/2019 and filed 02/14/2019) and GU et al (see Eur Respir Rev, 2020, Vol. 26, p. 1-12).
‘568 is drawn to compounds of formula
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and composition comprising said compounds, such as
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(see claim 22 of ‘568 which corresponds to compound 6 of instant claim 5) and methods for treating disease or disorder alleviated by TRPC6 inhibition using said compounds. The compounds of ‘568 correspond to the compounds embraced by methods of use in the instant application. Within ‘568, the compounds are taught to be inhibitors of TRPC6 and used to treat inflammatory diseases. “A claim to a method of using a composition is not patentably distinct from an earlier claim to the identical composition in a patent disclosing the identical use,” extends to any and all such uses disclosed in the specification of the earlier patent. See In Re Pfizer, 518 F.3d at 1363; Geneva, 349 F.3d at 1385-86.
Berry et al teach TRPC6 inhibitors may be useful to reduce the rate of mortality in sepsis, severe sepsis and septic shock as survival rate in model of system sepsis was significantly improved in TRPC6 deficient mice (see p. 7) and pharmaceutical compositions comprising said compounds contain at least about 5% but more preferably at least about 20 % (see p. 102). GU et al teach that sepsis is a complex syndrome that results from infection and defined as a life-threatening organ dysfunction resulting from dysregulated host responses to infection and that intravenous antibiotics within 1 hr after recognition of both sepsis and septic shock is strongly recommended. Bacteria have been shown to be the predominant pathogens of sepsis caused by infection and viruses were detected in around one-third of adult patients with sepsis. GU et al reference Kumar et al (Crit Care Med, 2006 Jun;34(6):1589-96) which teaches that effective antimicrobial administration within the first hour of documented hypotension was associated with increased survival to hospital discharge in adult patients with septic shock (see conclusion) and that onset of hypotension is a critical marker of increased mortality in a murine model of Escherichia coli peritonitis/septic shock. Thus, hypotension is taught to be a marker of septic shock.
Thus at the time of filing, it would have been obvious to utilize the compounds of ‘568 in view of Berry et al and GU et al to arrive at the methods of the instant claims. The compounds of ‘568 could be used to treat a systemic inflammatory response such as sepsis that occurs in response to a bacterial or fungal infection as these agents are generally found to be associated with sepsis. Berry et al teach TRPC6 inhibitors in treating sepsis while Gu et al teach sepsis usually is caused by bacteria and recommend effective antimicrobial administration within an hour to patients in septic shock. Thus, at the time of the invention, the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395; B/E Aerospace, Inc. v. C&D Zodiac, Inc., 962 F.3d 1373, 1379, 2020 USPQ2d 10706 (Fed. Cir. 2020).
Rejection III
Claims 1-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 3-5 and 15 of copending Application No. 17/914,773 in view of GU et al (see Eur Respir Rev, 2020, Vol. 26, p. 1-12). ‘773 teaches methods of treating disorder associated with vascular hyperpermeability and/or conditions arising therefrom comprising administering a compound of formula
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with claims 3 and 15 naming sepsis, severe sepsis and septic shock. Further claim 5 of ‘773 teaches compounds that correspond to those used in the method of the instant claims (see for example compound 1 of ‘773 correspond to compound 1 of instant claim 5).
GU et al teach that sepsis is a complex syndrome that results from infection and defined as a life-threatening organ dysfunction resulting from dysregulated host responses to infection and that intravenous antibiotics within 1 hr after recognition of both sepsis and septic shock is strongly recommended. Bacteria have been shown to be the predominant pathogens of sepsis caused by infection and viruses were detected in around one-third of adult patients with sepsis. GU et al reference Kumar et al (Crit Care Med, 2006 Jun;34(6):1589-96) which teaches that effective antimicrobial administration within the first hour of documented hypotension was associated with increased survival to hospital discharge in adult patients with septic shock (see conclusion) and that onset of hypotension is a critical marker of increased mortality in a murine model of Escherichia coli peritonitis/septic shock. Thus, hypotension is taught to be a marker of septic shock.
Thus at the time of filing, it would have been obvious to utilize the compounds of ‘773 in view of GU et al to arrive at the methods of the instant claims. The compounds of ‘773 could be used to treat a systemic inflammatory response such as sepsis that occurs in response to a bacterial or fungal infection as bacteria are generally found to be associated with sepsis. ‘773 teaches the same compounds for treating sepsis while Gu et al teach sepsis usually is caused by bacteria and recommend effective antimicrobial administration within an hour to patients in septic shock. Thus, at the time of the invention, the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395; B/E Aerospace, Inc. v. C&D Zodiac, Inc., 962 F.3d 1373, 1379, 2020 USPQ2d 10706 (Fed. Cir. 2020).
This is a provisional nonstatutory double patenting rejection.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAREN CHENG whose telephone number is (703)756-4699. The examiner can normally be reached M-F, 9AM-6PM PST.
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/KAREN CHENG/Primary Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
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