DETAILED ACTION
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 Claims
Claims 1-26 are pending. Claims 27 and 28 are cancelled.
Status of Priority
The present application is a 35 U.S.C. § 371 national stage patent application of International patent application PCT/SG2021/050523, filed on August 30, 2021. This application also claims the benefits of foreign priority to SG10202008397U, filed on August 31, 2020.
Specification - Abstract
The abstract of the disclosure is objected to because it can be more informative and descriptive. For example, the abstract may be amended as follows:
A method of treating a viral infection comprising administering a therapeutically effective amount of 2-(3,5- difluoro-3'methoxybiphenyl-4-ylamino)nicotinic acid, a dihydroorotate dehydrogenase (DHODH) inhibitor, either alone or in combination with another therapy to a patient in need thereof. The present invention also relates to formulations or compositions comprising the DHODH inhibitor suitable for treating a viral infection.
Appropriate correction is required.
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Objections
Claims 3, 5, and 13 are objected to because of the following informalities:
For consistency and to avoid 112(b) issues:
Claim 3 should read, “A method according to claim 1, wherein the viral infection is caused by a virus within the family Coronaviridae.”;
For consistency:
Claim 5 should read, “…wherein the virus is a Sarbecovirus.”;
Claim 13 should read, “genus Alphavirus”;
Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 2 is rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The term “suspect” or “suspected” is not defined by the instant specification. Accordingly, Examiner refers to the definition provided by the Merriam-Webster dictionary: “to imagine to exist or be true, likely, or probable.” Therefore, even if it is imagined to be true that a patient has a viral infection, the patient may, in reality, not have the viral infection at all. Administering a DHODH inhibitor to a non-infected patient would not result in a viral infection being treated as there was no viral infection to begin with. Hence, the invention lacks utility and the claim does not fall within at least one of the four categories of patent eligible subject matter.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-26 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention.
As stated in the MPEP 2164.01(a), “There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.”
In evaluating the enablement question, several factors are to be considered. According to In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988), these factors include:
1) The nature of the invention,
2) the state of the prior art,
3) the predictability or lack thereof in the art,
4) the amount of direction or guidance present,
5) the presence or absence of working examples,
6) the breadth of the claims, and
7) the quantity of experimentation needed, and
8) the level of the skill in the art.
In the instant case, the Wands factors are relevant for the following reasons:
The nature of the invention
The nature of the invention claims a method of treating a viral infection comprising administering a therapeutically effective amount of 2-(3,5- difluoro-3'methoxybiphenyl-4-ylamino)nicotinic acid, a dihydroorotate dehydrogenase (DHODH) inhibitor, either alone or in combination with another therapy to a patient in need thereof. The instant specification refers to this DHODH inhibitor as ASLAN003. According to the instant specification, the patient is human (pg. 3, item (23)).
State of the prior art
According to in vitro studies disclosed in the prior art, “[i]nhibiting DHODH activity can be considered to deplete intracellular pyrimidine pools, leading to suppression of viral RNA synthesis. [Further, the results] suggest that host proteins [i.e., the DHODH enzyme] could be targeted for development of DENV [i.e., dengue virus] therapeutics. However, translation of in vitro efficacy to in vivo efficacy of the host [i.e., DHODH] inhibitors remains to be achieved” (Wang, Q.-Y. et al. Inhibition of Dengue Virus through Suppression of Host Pyrimidine Biosynthesis. J. Virol. 2011, 85, 6548-6556.; pg. 6555, right col., last paragraph). In other words, while in vitro studies may suggest the clinical potential of the DHODH inhibitor, confirmation that the compound can treat a viral infection in a patient necessitates in vivo studies.
The amount of direction or guidance present and quantity of experimentation necessary
The prior art does not disclose a method of treating a viral infection by administering a therapeutically effective amount of ASLAN003 to a patient in need thereof. The instant specification only presents in vitro data and provides no in vivo evidence demonstrating the efficacy of ASLAN003 for treating viral infection in a human patient. Further, by stating that the disclosed in vitro experiments only “demonstrate the potential for ASLAN003 to be employed as an anti-viral agent,” the instant specification confirms that the disclosure lacks evidence demonstrating treatment of viral infection in human patients (pg. 21, last three lines). In the absence of clear guidance, a person of ordinary skill in the art would require undue experimentation to determine a therapeutically effective amount of ASLAN003 for treating a viral infection (caused by any virus in the family Coronaviridae or Flaviviridae or caused by a virus in the genus Flavivirus or Alphavirus) in a human patient.
The presence or absence of working examples
The instant specification only presents in vitro data and provides no in vivo evidence demonstrating the efficacy of ASLAN003 for treating viral infection in a human patient. Specifically, only in vitro data pertaining to SARS-Co-V-2, Dengue virus, Zika virus, and Chikungunya virus were provided. No in vitro or in vivo data pertaining to all virus in the family Coronaviridae or Flaviviridae or in the genus Flavivirus or Alphavirus were provided.
Additionally, there is no evidence provided in the instant specification demonstrating that a viral infection can be prevented in a human patient. Experimental evidence provided in the instant specification only demonstrates antiviral activity of ASLAN003 in vitro.
The breadth of the claims
The claims are broad insofar as the instant claims encompass methods of treating a viral infection in a patient wherein the viral infection can be caused by any virus within an entire family or genus. Specifically, the family Coronaviridae or Flaviviridae or the genus Flavivirus or Alphavirus.
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 3, 6, 7, 11, 17-19, 24, and 26 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.
Claim 3 recites the limitation "virus". There is insufficient antecedent basis for this limitation in the claim. Claim 3 depends on claim 1. Claim 1 does not mention a virus. It only mentions a viral infection.
Claim 7 recites the limitation "MERS-CoV". There is insufficient antecedent basis for this limitation in the claim. Claim 7 depends on claim 6. Claim 6 does not mention MERS-CoV. It only mentions SARS-CoV and SARS-CoV-2.
Regarding claims 6, 18, 19, 24, and 26, 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).
Regarding claim 11, the phrase "for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 17, the phrase "in particular" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Note on 35 USC §103 Rejections
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.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-21 and 26 are rejected under 35 U.S.C. 103.
Rejection – Part 1:
Claims 1, 2, 8-11, 16, 18, 19, and 26 are rejected under 35 U.S.C. 103 as being unpatentable over:
Vitt et al. (Vitt) (US20100280081A1; published November 4, 2010),
Ting et al. (Ting) (Ting, S. B. et al. Preliminary Results of a Phase 2a Dose Optimization Study of ASLAN003 (DHODH inhibitor) in Acute Myeloid Leukemia (AML) Patients Who Are Ineligible for Standard Therapy; Early Signs of Activity. Blood 2018, 132, 2676.
Vitt discloses compounds which inhibit dihydroorotate dehydrogenase (DHODH), for the treatment and prevention of viral diseases such as West Nile Virus (WNV), and Dengue Virus (DV) (pg. 1, para. 0002, 0008, and 0009). One of the DHODH inhibitors disclosed by Vitt has the following structure (pg. 36, compound 19):
PNG
media_image1.png
249
480
media_image1.png
Greyscale
(i.e., 2-(3,5-difluoro-3'-methoxybiphenyl-4-ylamino)nicotinic acid which is the same DHODH inhibitor disclosed in the instant claim set). As stated above, the instant specification refers to this DHODH inhibitor as ASLAN003.
Note: West Nile virus is a mosquito-borne Flavivirus which is a virus in the family Flaviviridae (Lucas-Hourani, pg. 3, left col., 2nd paragraph, 2nd to last sentence; sentence starts with “Similar results were obtained on West Nile virus…”).
Vitt does not disclose a safe dosage of ASLAN003. Ting is relied upon for this disclosure.
Ting discloses the safe administration of 100 mg and 200 mg doses of ASLAN003, a DHODH inhibitor, to acute myeloid leukemia (AML) patients (i.e., human patients; title and Results section, 1st sentence).
In summary, prior art (Ting) teaches that ASLAN003, a DHODH inhibitor, can be safely administered to human patients at doses of 100 mg and 200 mg. Additionally, prior art (Vitt) teaches that DHODH inhibitors have antiviral activity against viruses (including Dengue virus and West Nile virus [a virus from the genus Flavivirus]) in cells. Therefore, one of ordinary skill in the art would have found it prima facie obvious before the effective filing date of the claimed invention to try and administer ASLAN003 (a DHODH inhibitor) to treat viral infections (caused by viruses as listed above) in human patients at a dose of 100 mg or 200 mg.
Although Vitt does not explicitly demonstrate antiviral activity of ASLAN003, its teachings that (i) DHODH inhibitors are good candidates for treating viral infections (including dengue and West Nile virus) and (ii) ASLAN003 being disclosed as a DHODH inhibitor, provides motivation for the use of ASLAN003 in the treatment of viral infections in a patient wherein the viral infection is caused by a virus such as dengue or a Flavivirus like West Nile Virus.
Rejection – Part 2:
Claims 1-7, 16, 17, and 26 are rejected under 35 U.S.C. 103 as being unpatentable over:
Vitt et al. (Vitt) (US20100280081A1; published November 4, 2010),
Cheung et al. (Cheung) (Cheung, N. N. et al. Broad-spectrum inhibition of common respiratory RNA viruses by a pyrimidine synthesis inhibitor with involvement of the host antiviral response. Journal of General Virology 2017, 98, 946-954.),
Ting et al. (Ting) (Ting, S. B. et al. Preliminary Results of a Phase 2a Dose Optimization Study of ASLAN003 (DHODH inhibitor) in Acute Myeloid Leukemia (AML) Patients Who Are Ineligible for Standard Therapy; Early Signs of Activity. Blood 2018, 132, 2676.
The teachings of Vitt as they apply to claims 1, 2, 8-11, 16, 18, 19, and 26 are as discussed in “Rejection – Part 1” and incorporated herein.
Vitt does not disclose a DHODH inhibitor that has antiviral activity against SARS and MERS coronaviruses. Cheung is relied upon for this disclosure.
Cheung discloses that FA-613 (a DHODH inhibitor; pg. 947, right col., last paragraph, last sentence) showed antiviral activity against both SARS and MERS-coronaviruses (pg. 948 and 949, Discussion section, first two sentences).
Cheung does not disclose a safe dosage of ASLAN003. Ting is relied upon for this disclosure.
The teachings of Ting as they apply to claims 1, 2, 8-11, 16, 18, 19, and 26 are as discussed in “Rejection – Part 1” and incorporated herein.
In summary, prior art (Ting) teaches that ASLAN003, a DHODH inhibitor, can be safely administered to human patients at doses of 100 mg and 200 mg. Additionally, prior art teaches that DHODH inhibitors have antiviral activity against viruses (Vitt) (including SARS and MERS-coronaviruses as taught by Cheung) in cells. Therefore, one of ordinary skill in the art would have found it prima facie obvious before the effective filing date of the claimed invention to try and administer ASLAN003 (a DHODH inhibitor) to treat viral infections (caused by viruses as listed above) in human patients at a dose of 100 mg or 200 mg.
Although none of the prior art explicitly demonstrate antiviral activity of ASLAN003, its teachings that (i) DHODH inhibitors are good candidates for treating viral infections (Vitt and Cheung) and (ii) ASLAN003 being disclosed as a DHODH inhibitor (Vitt), provides motivation for the use of ASLAN003 in the treatment of viral infections in a patient wherein the viral infection is caused by SARS or MERS-coronaviruses.
Rejection – Part 3:
Claims 1-6, 8-10, 12, 16-19, and 26 are rejected under 35 U.S.C. 103 as being unpatentable over:
Vitt et al. (Vitt) (US20100280081A1; published November 4, 2010),
Xiong et al. (Xiong) (Xiong, R. et al. Novel and potent inhibitors targeting DHODH, a rate-limiting enzyme in de novo pyrimidine biosynthesis, are broad-spectrum antiviral against RNA viruses including newly emerged coronavirus SARS-CoV-2. BioRxiv 2020.; published March 12, 2020.),
Ting et al. (Ting) (Ting, S. B. et al. Preliminary Results of a Phase 2a Dose Optimization Study of ASLAN003 (DHODH inhibitor) in Acute Myeloid Leukemia (AML) Patients Who Are Ineligible for Standard Therapy; Early Signs of Activity. Blood 2018, 132, 2676.
The teachings of Vitt as they apply to claims 1, 2, 8-11, 16, 18, 19, and 26 are as discussed in “Rejection – Part 1” and incorporated herein.
Vitt does not disclose a DHODH inhibitor that has antiviral activity against Zika virus and SARS-CoV-2. Xiong is relied upon for this disclosure.
Xiong “identified two potent inhibitors of DHODH, S312 and S416, with favorable drug-like and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus (H1N1, H3N2, H9N2), Zika virus, Ebola virus, and particularly against the recent novel coronavirus SARS-CoV-2” (abstract).
Xiong does not disclose a safe dosage of ASLAN003. Ting is relied upon for this disclosure.
The teachings of Ting as they apply to claims 1, 2, 8-11, 16, 18, 19, and 26 are as discussed in “Rejection – Part 1” and incorporated herein.
In summary, prior art (Ting) teaches that ASLAN003, a DHODH inhibitor, can be safely administered to human patients at doses of 100 mg and 200 mg. Additionally, prior art teaches that DHODH inhibitors have antiviral activity against viruses (Vitt) (including Zika virus and SARS-CoV-2 as taught by Xiong) in cells. Therefore, one of ordinary skill in the art would have found it prima facie obvious before the effective filing date of the claimed invention to try and administer ASLAN003 (a DHODH inhibitor) to treat viral infections (caused by viruses as listed above) in human patients at a dose of 100 mg or 200 mg.
Although none of the prior art explicitly demonstrate antiviral activity of ASLAN003, its teachings that (i) DHODH inhibitors are good candidates for treating viral infections (Vitt and Xiong) and (ii) ASLAN003 being disclosed as a DHODH inhibitor (Vitt), provides motivation for the use of ASLAN003 in the treatment of viral infections in a patient wherein the viral infection is caused by SARS-CoV-2 or Zika virus.
Rejection – Part 4:
Claims 1, 2, 13-16, 18, 19, and 26 are rejected under 35 U.S.C. 103 as being unpatentable over:
Vitt et al. (Vitt) (US20100280081A1; published November 4, 2010),
Lucas-Hourani et al. (Lucas-Hourani) (Lucas-Hourani, M. et al. Inhibition of Pyrimidine Biosynthesis Pathway Suppresses Viral Growth through Innate Immunity. PLoS Pathog 2013, 9, e1003678.),
Ting et al. (Ting) (Ting, S. B. et al. Preliminary Results of a Phase 2a Dose Optimization Study of ASLAN003 (DHODH inhibitor) in Acute Myeloid Leukemia (AML) Patients Who Are Ineligible for Standard Therapy; Early Signs of Activity. Blood 2018, 132, 2676.
The teachings of Vitt as they apply to claims 1, 2, 8-11, 16, 18, 19, and 26 are as discussed in “Rejection – Part 1” and incorporated herein.
Vitt does not disclose a DHODH inhibitor that has antiviral activity against Chikungunya virus. Lucas-Hourani is relied upon for this disclosure.
Lucas-Hourani discloses that DD264 (a DHODH inhibitor; pg. 14, left col., 2nd paragraph, 1st sentence: “DD264 directly inhibits DHODH”) “efficiently suppressed CHIKV (i.e., chikungunya virus) growth in infected cell cultures” (pg. 3, left col., 2nd paragraph).
Lucas-Hourani does not disclose a safe dosage of ASLAN003. Ting is relied upon for this disclosure.
The teachings of Ting as they apply to claims 1, 2, 8-11, 16, 18, 19, and 26 are as discussed in “Rejection – Part 1” and incorporated herein.
In summary, prior art (Ting) teaches that ASLAN003, a DHODH inhibitor, can be safely administered to human patients at doses of 100 mg and 200 mg. Additionally, prior art teaches that DHODH inhibitors have antiviral activity against viruses (Vitt) (including Chikungunya virus as taught by Lucas-Hourani) in cells. Therefore, one of ordinary skill in the art would have found it prima facie obvious before the effective filing date of the claimed invention to try and administer ASLAN003 (a DHODH inhibitor) to treat viral infections (caused by viruses as listed above) in human patients at a dose of 100 mg or 200 mg.
Although none of the prior art explicitly demonstrate antiviral activity of ASLAN003, its teachings that (i) DHODH inhibitors are good candidates for treating viral infections (Vitt and Lucas-Hourani) and (ii) ASLAN003 being disclosed as a DHODH inhibitor (Vitt), provides motivation for the use of ASLAN003 in the treatment of viral infections in a patient wherein the viral infection is caused by Chikungunya virus.
Rejection – Part 5:
Claims 20 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over:
Coelho, A. R. et al. Dihydroorotate dehydrogenase inhibitors in SARS-CoV-2 infection. Eur J Clin Invest. 2020, 50, e13366.; published July 31, 2020.
Ting et al. (Ting) (Ting, S. B. et al. Preliminary Results of a Phase 2a Dose Optimization Study of ASLAN003 (DHODH inhibitor) in Acute Myeloid Leukemia (AML) Patients Who Are Ineligible for Standard Therapy; Early Signs of Activity. Blood 2018, 132, 2676.
Coelho states that although any individual can be infected by a virus like SARS-CoV-2, the clinical prognosis is worse for patients with one or more risk factors (such as age, obesity, hypertension, diabetes, respiratory and/or cardiovascular disease, and cancer, or autoimmune diseases, among others) (pg. 1, left col., 1st paragraph). Coelho also teaches that DHODH inhibitors prevent viral replication (pg. 2, Figure 1 caption, 1st sentence).
Coelho does not teach the DHODH inhibitor, ASLAN003. Ting is relied upon for this disclosure.
The teachings of Ting as they apply to claims 1, 2, 8-11, 16, 18, 19, and 26 are as discussed in “Rejection – Part 1” and incorporated herein
Since the clinical prognosis of patients with viral infections is worse in those with one or more risk factors such as cancer, a POSITA would be motivated to find a drug that can act as both an antiviral agent and, for example, an anticancer agent. ASLAN003 would be a good drug choice as it satisfies the motivation for a dual-purpose drug: ASLAN003 not only is a DHODH inhibitor which can have antiviral activity (Coelho; also explained in Rejection Parts 1-4 above), it is also known in the art that ASLAN003 treats AML patients (as taught by Ting) (reads on instant claims 20-21). Thus, one of ordinary skill in the art would have found it prima facie obvious before the effective filing date of the claimed invention to treat a viral infection in a patient who has co-morbidities.
Thus, claims 1-21 and 26 are rejected under 35 U.S.C. 103
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 1-6 and 8-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over:
claims 29-34 of U.S. Patent Application No. 18/835,823 (‘823) in view of
Lee, E. H. A practical guide to pharmaceutical polymorph screening & selection. Asian Journal of Pharmaceutical Sciences 2014, 9, 163-175.
Although the claims at issue are not identical, they are not patentably distinct from each other because there is overlap between the instant claims and the claim set from the co-pending application.
Claims 29-34 of ‘823 are directed towards a method of treating a viral infection or an autoimmune disease comprising administering a therapeutically effective amount of a polymorph of 2-(3,5- difluoro-3'methoxybiphenyl-4-ylamino)nicotinic acid (i.e., the DHODH inhibitor discussed in the instant application) to a subject in need thereof. According to claim 30, the viral infection is caused by a virus selected from the group comprising: dengue (such as serotypes 1, 2, 3, or 4), Zika, Chikungunya, and SARS-CoV-2.
Claims 1-6 and 8-19 of the instant claim set are directed towards a method of treating a viral infection, comprising administering a therapeutically effective amount of 2-(3,5- difluoro-3'methoxybiphenyl-4-ylamino)nicotinic acid to a patient in need thereof. According to the instant claim set, the viral infection is caused by dengue virus (encompassed by instant claims 1, 2, 8-11, 16, 18, and 19), Zika virus (encompassed by instant claims 1, 2, 8-10, 12, 16, 18, and 19), Chikungunya virus (encompassed by instant claims 1, 2, 13-16, 18, and 19), and SARS-CoV-2 (encompassed by instant claims 1-6, 16, 17, and 19).
According to Lee, “[i]mprovements in physicochemical properties can be achieved by altering the physical forms of a given compound such as polymorphs” (pg. 163, Introduction section, right col., 2nd paragraph, 1st sentence). The physicochemical properties that can be altered by choosing different polymorphs include kinetic properties such as dissolution rate (pg. 164, left col., Table 1). In other words, polymorphism is purely a solid-state phenomenon that can influence physicochemical properties of a drug such as dissolution rate. When the polymorph of the nicotinic acid (from claims 29-34 of ‘823) is dissolved in vivo, the crystal lattice of the polymorph is lost, and the dissolved species would have the same molecular structure as the nicotinic acid in instant claims 1-6 and 8-19.
Thus, a method of treating a viral infection or an autoimmune disease comprising administering a therapeutically effective amount of a polymorph of 2-(3,5- difluoro-3'methoxybiphenyl-4-ylamino)nicotinic acid to a subject in need thereof (as disclosed in claims 29-34 of ‘823) are not patentably distinct from claims 1-6 and 8-19 of the instant claim set which is directed towards a method of treating a viral infection, comprising administering a therapeutically effective amount of 2-(3,5- difluoro-3'methoxybiphenyl-4-ylamino)nicotinic acid to a patient in need thereof.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KRISTEN ROMERO whose telephone number is (571)272-6478. The examiner can normally be reached M-F 9:30 AM - 6:00 PM ET.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JEFFREY H. MURRAY can be reached at (571) 272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/KRISTEN W ROMERO/Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624