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
This application, filed 7 August, 2024, is a national stage application of PCT/GB2023/050296, filed 9 February, 2023, which claims foreign benefit of application TW111104639, filed 9 February, 2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 7 August, 2024 is acknowledged and has been considered.
Status of the Application
Receipt is acknowledged of Applicant's claimed invention, filed 7 August, 2024, in the matter of Application N° 18/836,532. Said documents have been entered on the record.
Claims 3-14 have been amended. No new matter was introduced.
Thus, Claims 1-14 represent all claims currently under consideration.
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 4 and 11 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 written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 4 recites that the pharmaceutical combination “further comprises one or more preservatives selected from the group consisting of an antibacterial agent, an antifungal agent, and an antiseptic.” However, the originally filed specification does not describe preservatives or identify antibacterial agents, antifungal agents, or antiseptic agents as components of the disclosed pharmaceutical combinations or pharmaceutical compositions. Rather, the specification identifies pharmaceutically acceptable excipients generally and specifically describes diluents, binders, lubricants, and disintegrants, without describing preservatives or the claimed subclasses thereof. Accordingly, the originally filed disclosure does not reasonably convey possession of the subject matter of claim 4.
Claim 11 recites “wherein the combination significantly increases the expression of nitric oxide synthase in a cell.” However, the specification does not reasonably convey possession of increasing the expression of nitric oxide synthase generally in a cell. Rather, the instant specification describes only the expression of vascular endothelial nitric oxide synthase following treatment of vascular endothelial cells, as evidenced by the description of Figure 3 and the associated experimental results. Accordingly, while the specification provides written descriptive support for increased expression of vascular endothelial nitric oxide synthase (eNOS) in vascular endothelial cells, it does not provide written descriptive support for the broader limitation of increasing the expression of nitric oxide synthase in a cell, as presently claimed. The claimed limitation encompasses additional nitric oxide synthase isoforms and cell types that are not described in the specification. Therefore, the originally filed disclosure does not reasonably convey possession of the subject matter of claim 11.
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 and 8-9 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 1 recites, “optionally, the pharmaceutical combination is in the form of a pharmaceutical composition comprising a pharmaceutically acceptable excipient.” The recitation of “optionally” renders it unclear whether the pharmaceutical composition comprising the pharmaceutically acceptable excipient is a required limitation of the claim or merely an unclaimed embodiment. Accordingly, the metes and bounds of the claimed subject matter cannot be determined with reasonable certainty.
Claim 8 recites, “a disease associated with inhibition of PDE5.” It is unclear whether this phrase refers to (i) a disease resulting from inhibition of PDE5, (ii) a disease treated by inhibition of PDE5, or (iii) a disease otherwise associated with inhibition of PDE5. Accordingly, the scope of the claimed disease is uncertain.
Claim 9, which depends upon Claim 8, does not resolve this ambiguity because the listed diseases (e.g., erectile dysfunction and pulmonary hypertension) identify exemplary diseases but do not clarify the nature of the claimed association with inhibition of PDE5.
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 1-3, 5-10 and 12-14 are rejected under 35 U.S.C. 103 as being unpatentable over Shell and Jarmel (WO00/000212 A1, cited in IDS) and further in view of Laniado et al. (WO 01/28541 A2, cited in IDS), hereinafter Laniado.
Regarding Claims 1-2, Shell and Jarmel teach compositions comprising sildenafil as the phosphodiesterase inhibitor, together with the NO agonist, such as n-acetyl cysteine, and NO precursor, such as arginine (‘212, Abstract, Pg. 5, Lines 28-30, Examples 1 and 6).
Regarding Claim 3, Shell and Jarmel teach the sildenafil dosage is desirably at or below about 20 mg (‘212, Pg 16, Lines 10-11), the thioamino acids at dosage levels of from about 20 to 800 mg (‘212, Pg 15, Lines 21-22), and arginine is 10 to 1,000 mg (‘212, Pg 14, Line 24).
Regarding Claims 5-6, Shell and Jarmel teach the dosage forms include capsules, caplets, chewable wafers, tablets, liquid suspensions, powders and the like (‘212, Pg 16, Lines 23-24).
Regarding Claims 7-9 and 13, Shell and Jarmel teach these formulations are used in the treatment of NO and/or cGMP insufficiency, and particularly conditions involving the cardiovascular, pulmonary and reproductive systems, such as erectile dysfunction (‘212, Abstract).
Regarding Claim 12, Shell and Jarmel teach a phosphodiesterase inhibitor is administered concomitantly with the NO precursor and NO agonist (‘212, Pg 5, Lines 2-3).
Regarding Claim 10, Laniado teaches that administration of sildenafil together with arginine improves the onset and duration of sildenafil activity compared to sildenafil administered alone, as evidenced by the treatment examples demonstrating satisfactory erectile response following administration of the combination and prolonged activity relative to sildenafil alone (‘541, Examples 2 and 4).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to formulate and administer a pharmaceutical combination comprising a phosphodiesterase type 5 (PDE5) inhibitor, such as sildenafil, together with arginine and N-acetylcysteine, as taught by Shell and Jarmel, because the reference teaches promoting nitric oxide (NO) production and cGMP activity through concomitant administration of an NO precursor, such as arginine, an NO agonist, such as N-acetylcysteine and a PDE5 inhibitor, while Laniado further teaches that the specific combination of sildenafil and arginine improves therapeutic efficacy, prolongs activity, and reduces adverse effects relative to sildenafil alone. One of ordinary skill in the art would have recognized that Laniado’s sildenafil/arginine combination represents a preferred implementation of the NO/cGMP-promoting therapeutic approach disclosed by Shell and Jarmel and would have been motivated to incorporate that known combination into the compositions of Shell and Jarmel, including the N-acetylcysteine-containing embodiments, in order to predictably enhance endothelial relaxation, improve vascular function, and reduce adverse effects associated with PDE5 inhibitor therapy. Because both references are directed to improving the same NO/cGMP signaling pathway through complimentary mechanisms, a person of ordinary skill in the art would have had a reasonable expectation of success in combining their teachings.
Communication
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Donna M. Nestor whose telephone number is (703)756-5316. The examiner can normally be reached generally (w/flex): 5:30a-5p EST M-Th.
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/D.M.N./ Examiner, Art Unit 1627
/SARAH PIHONAK/ Primary Examiner, Art Unit 1627
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