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 .
Status of the Claims
Claims 1-19 are pending.
Claims 4-6 and 15-19 are withdrawn.
Priority
Applicant’s claim for benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. This application is a national stage entry of and claims priority to Application Serial No. PCT/EP2021/000071, filed 6/09/2021; and further claims priority to FOR application numbers EP20000366.3 and EP20000212.9, filed 10/08/2020 and 06/10/2020, respectively.
Information Disclosure Statement
All references from IDS(s) received on 07/07/2023 and 05/04/2026 have been considered unless marked with a strikethrough.
Response to Arguments
Applicant’s arguments filed 5/01/2026, with respect to the rejections of claims 1-3, 7-14, and 20-27 under 35 U.S.C. 112 and 103 have been fully considered and are found not persuasive.
The Applicant amended claims 1-3 and 7-14 to remove the word “use” and to include the word “or” in between the d values and theta values. This satisfies the issues of the 112(d) rejection and therefore this rejection is moot and withdrawn. This, however, does not satisfy the issues of the 112(a) rejection. The Applicant has not addressed that there are no working examples of how the polymorph is formed (crystallized, purified, etc.). The Applicant mentions the Bragg equation however this is for calculating the values claimed not how to obtain the product. The Applicant mentions the product is obtained from/provided by MetrioPharm, but this is the Applicant. Therefore, there should be a method or an example for obtaining the product with these d/theta values. Therefore, the 112(a) rejection is maintained.
With respect to the 102 rejection, the Applicant argues that the prior art provided by the Examiner (“Martin”) has a priority date of 2016, while SARS-CoV-2 was not reported until 2020. The Examiner argues that Martin teaches the compounds for use in the prophylaxis or treatment of an inflammatory or respiratory disease. SARS-CoV-2, is apart of the family of SARS viruses, where SARS-CoV-1 was first reported on around 2002. The SARS viruses are known as inflammatory or respiratory diseases (Hasoksuz, M. et al. Turk J Med Sci (April 2020) 50: 549-556). Therefore, a person skilled in the art would assume that SARS-CoV-2 would fall under an inflammatory or respiratory disease. A 103 rejection is made in lieu of the previous 102 rejection.
MAINTAINED/NEW REJECTIONS
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.
Claim 3 is 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 claim(s) contains 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 make and/or use the invention.
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (1) The breadth of the claims, (2) The nature of the invention, (3) The state of the prior art, (4) The level of one of ordinary skill, (5) The level of predictability in the art, (6) The amount of direction provided by the inventor, (7) The existence of working examples and (8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Nature of the invention:
The invention is drawn to a sodium salt form of 5-amino-2,3-dihydro-1,4-phthalazinedione and its 3 crystalline anhydrate polymorph forms.
Breadth of the claims:
The claim is broadly directed to various polymorph forms of 5-amino-2,3-dihydro-1,4-phthalazinedione where the form used an be any or more than one of the three. The varying forms are listed below.
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Level of ordinary skill in the art/ State of the prior art and predictability in the art:
The artisans using applicant’s method would be a collaborative team of synthetic chemists and/or health practitioners, possessing commensurate degree level and/or skill in the art, as well as several years of professional experience.
The range of values varies from those taught in the art (see WO2017140430A1, US20170368063A1 and US20230053455A1 as examples). The polymorph forms taught in the art include a synthetic explanation, along with data evidence, to support its polymorph form. Polymorph formation is historically unpredictable (Laird, T. Org. Process Res. Dev. (2010) 14 (1): 1.). For further example, the ‘430 publication teaches the same compound as the instant application with the following D-values 11.8; 9.8; 9.2; 8.7; 8.1 ; 7.0; 6.8; 6.6; 3.4; 3.3; 3.3 and the following theta values: 7.5; 9.0; 9.6; 10.2; 10.9; 12.6; 13.1 ; 13.4; 25.9; 26.7; 27.2. This publication recites form II of the polymorph is formed using the following steps(Ex 2):
Providing a stirred solution of Na-luminolate in demineralized water;
Adding hydrochloric acid (10 to 38 %) to said solution in a temperature range of 5 to 50°C over a period of 1 sec to 60 min
Filtering and eashing the precipitate with demineralized water and then drying the precipitate at room temperature for 6-48 hours.
On the other hand, the ‘063 publication reports d values: 13.131; 7.987; 7.186; 6-566; 6.512; 5.372; 3.994; 3.662; 3.406; 3.288; 3.283; 3.222; 3.215; 3.127; 2.889 and theta values: 6.73; 11.07; 12.31; 13.48; 13.59; 16.49; 22.24; 24.29; 26.14; 27.10; 27.14; 27.67; 27.72; 28.52; 30.93. This publication reports the following production steps (para 0066):
10 g of 5-amino-2,3-dihydrophthalazine-1,4-dione sodium salt were solved in 3.3 L DMSO while stirring at 90° C. until apparently there was no more turbidity.
The solution was further stirred by applying a vacuum (8×10−3 mbar±1×103 mbar) at 90° C. until a suspension was generated. The suspension was dried at 90° C. under vacuum (8×10−3 mbar±1×10−3 mbar) until a solid was generated.
The solid was suspended in 2-propanol and filtered under vacuum utilizing a Büchner funnel. It was rinsed twice with 2-propanol.
Subsequently, the crystalline solid was dried at 50° C. in a drying cabinet to constant mass. After drying all forms produced were vortexed for 1 minute to let bigger agglomerates carefully disaggregate.
It is clear that the method of production and purification plays a role in the polymorph d- and theta values.
The instant application does not provide details of how the polymorph is formed (how its crystallized, purified, etc.) or any data to support the theta and d-values claimed. Therefore, the polymorph production would be unpredictable to a person skilled in the art at the time.
The amount of direction provided and working examples:
The only direction or guidance present in the instant specification is the disclosure of where the salt of the compound was obtained from. There are no working examples of how to achieve the polymorph forms claimed in the instant application.
See MPEP 2164.02 (“Compliance with the enablement requirement of 35 USC 112, first paragraph, does not turn on whether an example is disclosed ... Lack of a working example, however, is a factor to be considered, especially in a case involving an unpredictable and undeveloped art.”).
Quantity of experimentation needed to use the invention based on the content of the disclosure:
The quantity of experimentation needed is undue experimentation. One of skill in the art would need to determine through undue experimentation how to prepare the polymorph in a way that is different from the prior art that would lead to these different d-values.
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation.
Genentech Inc. v. Novo Nordisk A/S (CAFC) 42 USPQ2d 1001, states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable”.
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 1-2 and 7-14 are rejected under 35 U.S.C. 103 as being unpatentable over Martin, T. et al. (WO2017140430A1; cited in the IDS filed 7/7/2023; “Martin”) in further view of Marx, D. (Throat Spray Systems, Drug Development and Delivery, May 2018. https://drug-dev.com/throat-spray-systems-key-considerations-when-developing-a-throat-spray-solution/) and Hasoksuz, M. et al. (Turk J Med Sci (April 2020) 50: 549-556; “Hasoksuz”)
Martin teaches a crystalline polymorph form of 5-amino-2,3-dihydrophthalazine-1,4-dione (Claim 1), as well as its sodium salt (Page 2, Lines 25-26) for use in the prophylaxis or treatment of an inflammatory or respiratory disease (Claim 13), as required by instant claims 1-2. Martin teaches the pharmaceutical formulations for oral administration can be capsules or tablets, sugar-coated tablets or pills; powders or granulates; juices, syrups, drops, teas, solutions or suspensions in aqueous or non-aqueous liquids; edible foams or mousses; or in oil-in-water or water-in-oil in lotions (Page 9, Lines 24-27), as required by instant claims 7 and 20.
Martin also teaches pharmaceutical formulations of the compounds for use according to the invention can be administered by any suitable way, e.g. orally (incl. buccally and sublingually), rectally, vaginally, nasally, inhalatory, respiratory, alveolary, topically (incl. buccally, sublingually, conjunctivally or transdermally), or parenterally (incl. intraperitoneally, subcutaneously, intramuscularly, intravenously, intraarterially or intradermally) (Page 7, Last para.), as required by instant claims 7-8, 11-12.
Finally, Martin teaches the aerosols can be delivered to the patient through a nebulizer that uses oxygen, compressed air or ultrasonic power to produce aerosol droplets from a medical solution or suspension and direct them to a mouthpiece used by the patient for inhalation (Page 22, First para.), as required by instant claim 9.
Martin fails to explicitly teach the use of a cardiopulmonary bypass device, as required by instant claim 10. However, the claim limitations require the administration through the ventilation air of the device. Since Martin teaches aerosols and different methods of administration through devices using ventilation, it would be obvious to a person skilled in the art to use any device known for delivering compounds through ventilation.
Martin fails to explicitly teach pharyngeal administration or throat spray. However, Martin does teach the administration of aerosol droplets. Marx teaches that throat spray, as required by instant claim 14, is mechanized through aerosolized medical solution (or droplets). Therefore, it would be obvious to a person skilled in the art to extract the teachings of Martin and apply them to pharyngeal administration, aka throat spray.
Martin fails to teach the use of the compound for explicitly SARS-CoV-2. However, SARS-CoV-2, is apart of the family of SARS viruses, where SARS-CoV-1 was first reported on around 2002. The SARS viruses are known as inflammatory or respiratory diseases, as taught by Hasoksuz. Therefore, a person skilled in the art would assume that SARS-CoV-2 would fall under an inflammatory or respiratory disease.
The Supreme Court in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham.
Examples of rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Applying KSR example rationale (B), it would have been prima facie obvious to extract the use of 5-amino-2,3-dihydrophthalazine-1,4-dione for use in the prophylaxis or treatment of an inflammatory or respiratory disease, as taught by Martin, and substitute any of the diseases for SARS-CoV-2. A person skilled in the art would be motivated to do so because SARS, including SARS-CoV-2, is an inflammatory or respiratory disease, as taught by Hasoksuz.
Applying KSR example rationale (A), it would have been prima facie obvious to extract the use of 5-amino-2,3-dihydrophthalazine-1,4-dione for administered using nasal inhalation and apply it to a cardiopulmonary bypass device or pharyngeal administration. A person skilled in the art would be motivated to do so because Martin teaches aerosols and different methods of administration through devices using ventilation, as well as the administration of aerosol droplet. It would be obvious to a person skilled in the art to use any device known for delivering compounds through ventilation, such as the ventilation air of the cardiopulmonary bypass device, as required by claim 10. Further, it would be obvious to apply it to throat spray/pharyngeal administration because Marx teaches that throat spray, as required by instant claim 14, is mechanized through aerosolized medical solution (or droplets)
Therefore, claims 1-2 and 7-14 would be considered obvious to a person skilled in the art at the time.
Conclusion
Claims 1-3 and 7-14 are rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NICOLA MARIA BAUER whose telephone number is (703)756-1269. The examiner can normally be reached Monday-Friday 7:30-5 EST.
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, Clint Brooks can be reached at (571) 270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/N.M.B./Examiner, Art Unit 1621
/CLINTON A BROOKS/ Supervisory Patent Examiner, Art Unit 1621
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