DETAILED ACTION
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
The instant application is the national stage entry of PCT/EP2023/064970 filed 5 June 2023. Acknowledgement is made of the Applicant’s claim of foreign priority to EP22177930.9 filed 8 June 2022.
Information Disclosure Statement
The information disclosure statement filed 24 February 2026 fails to comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609 because the document contained mostly blank sheets and no list of references. Applicant is advised that the date of any re-submission of any item of information contained in this information disclosure statement or the submission of any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the statement, including all certification requirements for statements under 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.
Claim 16 is 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 16 recites, “wherein the chemotherapeutic agent is 5-fluorouracil or a derivative.” The claim does not define what “a derivative” is referring to nor does it define the metes and bounds thereof. As such, it is unclear and indefinite as to the scope of the term “derivative.”
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.
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 1-17 are rejected under 35 U.S.C. 103 as being unpatentable over Moser et al. (US 2017/0233394).
Moser teaches a preparation comprising between 10-3,000 mg of (6R)-5,10-CH2-THF in a daily dose, which reads on the compound of instant claim 1 [0062, 0125]. The dosage can be adjusted depending on the therapy and the age, weight, and condition of the patient [0126]. In one example, a lyophilizate of the sulfate salt of 5,10-methylene-(6R)-tetrahydrofolic acid is prepared with the presence of citrate wherein the lyophilizate can be reconstituted in water [0308]. The ratio of 5,10-methylene-(6R)-tetrahydrofolic acid to sulfate ion can be about 2:1 [0154]. The formulation can be used to treat forms of cancer and can be formulated with additional agents such as 5-fluorouracil and antifolate agents [0017, 0307]. Regarding the salt, Moser teaches that the sulfate salt form can be made from alkali or alkaline earth metal salts such as sodium and calcium [0100-0101]. The formulation may be prepared as a concentrate [0121]. The water can be sterile water and the composition can further comprise carriers and buffers [0120-0121, 0123]. The purity of the 5,10-methylene-(6R)-tetrahydrofolic acid is preferred to be greater than 99.5% [0172].
Moser does not teach the claimed composition in a single embodiment.
It would have been prima facie obvious to prepare the reconstituted aqueous formulation comprising 5,10-methylene-(6R)-tetrahydrofolic acid and a sulfate salt of Moser and to modify it so that the sulfate is from the inclusion of sodium sulfate (1:2 ratio of active to sulfate salt). It would have been obvious to purify the 5,10-methylene-(6R)-tetrahydrofolic acid to be greater than 99% pure. The form of the liquid composition can be as a concentrate using sterile water, carriers, and buffers, based on the alternatives taught in Moser, in a composition to treat various cancers. Moreover, it would have been obvious to further include 5-fluorouracil and/or antifolates as chemotherapeutic agents. That being said, it must be remembered that “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious.” KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious,” the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR at 1741. The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742. Consistent with this reasoning, it would have been obvious to have selected various combinations of counter ions and salts, forms of the composition, and additional chemotherapeutic agents from within Moser, to arrive at compositions “yielding no more than one would expect from such an arrangement.”
Regarding the amount of 5,10-methylene-(6R)-tetrahydrofolic acid, the art teaches dosing anywhere from 10-3,000 mg/day that can be adjusted based on the specific situation and needs of the patient. 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). MPEP 2144.05 (I).
The composition of Moser accordingly renders obvious instant claims 1-17.
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 1-17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-4, and 15-18 of copending Application No. 18/869,144 in view of Moser et al. (US 2017/0233394).
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘144 does not teach the sulfate as being an alkali metal sulfate. Moser teaches forming a concentrate of a sulfate salt of 5,10-methylene-(6R)-tetrahydrofolic acid using a metal salt such as sodium or calcium. Moser also teaches further including various chemotherapeutic agents, buffers, carriers, and sterile water to the formulation. It would have been prima facie obvious to prepare the composition of ‘144 wherein sodium sulfate is provided in a 1:2 ratio with 5,10-methylene-(6R)-tetrahydrofolic acid to form the sodium salt and to further include sterile water, buffer, carriers, and chemotherapeutics as needed. The resulting composition renders obvious instant claims 1-17.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 9-14, 16-17, and 21-22 of copending Application No. 18/869,153 in view of Moser et al. (US 2017/0233394).
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘153 does not teach the sulfate as being an alkali metal sulfate. Moser teaches forming a concentrate of a sulfate salt of 5,10-methylene-(6R)-tetrahydrofolic acid using a metal salt such as sodium or calcium. Moser also teaches further including various buffers, carriers, and sterile water to the formulation. It would have been prima facie obvious to prepare the composition of ‘153 wherein sodium sulfate is provided in a 1:2 ratio with 5,10-methylene-(6R)-tetrahydrofolic acid to form the sodium salt and to further include sterile water, buffer, and carriers as needed. The resulting composition renders obvious instant claims 1-17.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDREW S ROSENTHAL whose telephone number is (571)272-6276. The examiner can normally be reached M-F 8-5pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brian Kwon can be reached at 571-272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ANDREW S ROSENTHAL/ Primary Examiner, Art Unit 1613
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