NON-FINAL REJECTION
This application is a 35 U.S.C. 371 (national stage) application of PCT/US2021/070372, filed Apr. 9, 2021, which claims benefit of priority to Provisional Application 63/007,471, filed Apr. 9, 2020.
Claims 1-20, as amended, are pending.
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
Acknowledgment is made of applicant's claim to foreign priority under 35 U.S.C. 119(a)-(d).
Information Disclosure Statement
The information disclosure statements (IDS) submitted on Oct. 4, 2022 and Aug. 14, 2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Election/Restrictions
Applicant’s election without traverse of pemetrexed as the species of antifolate compound, and SARS coronavirus as the species of viral pulmonary infection to be treated, in the reply filed on Aug. 14, 2025 is acknowledged.
Claim 6 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on Aug. 14, 2025.
Claims 1-5 and 7-20 are currently pending and under consideration.
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)(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 1-5 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Bonnac et al. (US Pub. 2022/0273689, of record).
Bonnac et al. claim methods of treating an RNA virus infection comprising administering a combination of therapeutically effective amounts of (i) an antiviral nucleobase and (ii) a de novo nucleotide biosynthesis inhibitor (DNNBi) or a pharmaceutically acceptable salt thereof (claim 1).
The RNA virus infection is, e.g., severe acute respiratory syndrome (SARS) virus, Middle East Respiratory syndrome (MERS) coronavirus, SARS-CoV-2, respiratory syncytial virus, or influenza A (claim 2).
The de novo nucleotide biosynthesis inhibitor (DNNBi) is selected from a folate synthesis inhibitor, e.g., pemetrexed (claim 9).
Thus, Bonnac et al. disclose and claim methods of treating viral pulmonary infections caused by a coronavirus, e.g., SARS coronavirus, comprising administering a therapeutically effective amount of an antifolate, e.g., pemetrexed, as recited by claims 1-5.
As evidenced by the instant specification (p. 14, line 5 to p. 15, line 1), pemetrexed has the structure of formula (II), as recited by claim 3:
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which reads on formula (I) as recited by claim 2, wherein X is CH; R1 is hydrogen; and R2 is
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For the foregoing reasons, Bonnac et al. anticipates claims 1-5.
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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) 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 1-5 and 7-20 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Bonnac et al. (US Pub. 2022/0273689, of record) in view of Mandal et al. (US Pub. 2017/0340639, cited on PTO-892).
Bonnac et al. claim methods of treating an RNA virus infection comprising administering a combination of therapeutically effective amounts of (i) an antiviral nucleobase and (ii) a de novo nucleotide biosynthesis inhibitor (DNNBi) (DNNBi) or a pharmaceutically acceptable salt thereof (claim 1).
The RNA virus infection is, e.g., severe acute respiratory syndrome (SARS) virus, Middle East Respiratory syndrome (MERS) coronavirus, SARS-CoV-2, respiratory syncytial virus, or influenza A (claim 2).
The de novo nucleotide biosynthesis inhibitor (DNNBi) is selected from a folate synthesis inhibitor, e.g., pemetrexed (claim 9).
Thus, Bonnac et al. disclose and claim methods of treating viral pulmonary infections caused by a coronavirus, e.g., SARS coronavirus, comprising administering a therapeutically effective amount of an antifolate, e.g., pemetrexed, as recited by claims 1-5.
As evidenced by the instant specification (p. 14, line 5 to p. 15, line 1), pemetrexed has the structure of formula (II), as recited by claim 3:
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which reads on formula (I) as recited by claim 2, wherein X is CH; R1 is hydrogen; and R2 is
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The compositions of Bonnac et al. are disclosed for suitable routes of administration, e.g., parenterally, including subcutaneous, intramuscular, intravenous, intradermal, etc.; and where the compound is administered parenterally, it may be formulated in a unit dosage injectable form (para. [0128]), which reads on parenteral administration by intravenous (IV) injection, as recited by claims 7 and 8.
Bonnac et al. disclose that suitable aqueous solvents include, e.g., water, (para. [0125]), implicitly disclosing formulations in the form of an aqueous solution, as recited by claim 13.
Bonnac et al. disclose that a dose to treat human patients may range from about 1 mg to about 2000 mg of DNNBi (i.e., pemetrexed) (para. [0129]), which encompasses the dosages recited by claims 9, 10, and 18-20.
Bonnac et al. differs from the instant claims in that the reference does not disclose the specific components, amounts, and/or dosages recited by claims 9-20.
Mandal et al. disclose liquid ready-to-use injections comprising pemetrexed (abstract), in a concentration of 5-100 mg/ml (para. [0021]), comprising water for injection as a vehicle (para. [0033]), i.e., in the form of an aqueous solution, as recited by claim 13.
It is implicit in a "ready-to-use" injection that the route of administration is via intravenous bolus injection, as recited by claims 8, 16, and 17.
Mandal et al. exemplify formulations comprising pemetrexed at a concentration of 10 mg/ml (Examples 1-5; claim 20), and 1.0 mg/ml sodium disulfite (Example 4).
Mandal et al. further exemplify pemetrexed formulations comprising L-cysteine hydrochloride (para. [0145]); and disclose pemetrexed formulations comprising L-cysteine (claim 13) and sodium sulfite (para. [0018]; claim 14), as recited by claims 11, 12, and 14.
The cited references differ from the instant claims in that the references do not specify the exact dosages and amounts of components of the claimed formulations:
comprising about 2 % w/w to about 10 % w/w of antifolate, 0.04 % w/w to about 0.2 % w/w cysteine hydrochloride monohydrate, and 0.1 % w/w to about 0.95 % w/w sodium sulfite, as recited by claim 14, or
wherein the osmolality of the formulation is from about 250 mOsm to about 400 mOsm, as recited by claim 15;
or pemetrexed dosages in the amount of:
from about 0.01 mg/m2 to about 700 mg/m2 of body surface area, as recited by claim 9;
from about 0.2 mg to about 300 mg, as recited by claim 10;
from about 0.1 mg/m2 to about 150 mg/m2 of body surface area, as recited by claim 18;
from about 25 mg/m2 to about 100 mg/m2 of body surface area, as recited by claim 19; or
from about 35 mg/m2 to about 75 mg/m2 of body surface area, as recited by claim 20.
However, the cited references disclose compositions comprising each of the claimed components, and the administration of pemetrexed in some amount.
For example, Bonnac et al. teach a pemetrexed dosage of 1-2000 mg (para. [0129]); and Mandal et al. claim liquid compositions for parenteral administration comprising 5 to 100 mg/ml of pemetrexed or a pharmaceutically acceptable salt thereof (claim 11).
As recognized by MPEP § 2144.05,
Generally, differences in concentration or tempera-ture will not support the patentability of subject mat-ter 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 dis-cover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Therefore, it would have been predictable to an ordinarily skilled clinician as of the filing date to modify the pemetrexed amounts and dosages disclosed by Bonnac et al. and Mandal et al. to arrive at the claimed compositions with a reasonable expectation of success, because adjusting drug dosages based on patient-specific variables are a routine aspect of the clinician's work. Further, "the normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages." In re Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARA E. TOWNSLEY whose telephone number is 571-270-7672. The examiner can normally be reached on Mon-Fri from 9:00 am to 6:00 pm (EST). If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Jeff S. Lundgren, can be reached at 571-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SARA ELIZABETH TOWNSLEY/Examiner, Art Unit 1629