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 .
DETAILED ACTION
The preliminary amendment dated 23 January 2024, in which claims 1-18 have been amended, and new claim 19 has been added, is acknowledged.
Claims 1-19 are pending in the instant application.
Claims 7, 8 are withdrawn, as being drawn to a non-elected species.
Claims 1-6, 9-19 are being examined on their merits herein.
Priority
The instant application is a National Stage entry of International Application No. PCT/EP2022/055794, filed on 8 March 2022, claiming priority to European Patent Applications No. 21199700.2, filed on 29 September 2021; and 21161224.7, filed 8 March 2021.
Certified copies of the priority documents, in English, were submitted on 5 September 2023.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 31 January 2024 and 15 May 2026 are acknowledged and considered.
Election/Restrictions
Applicant’s election without traverse of DZNep or a pharmaceutically acceptable salt thereof as the species of an inhibitor of at least one S-adenosylmethionine (SAM) cycle; the election of DZNep and FIDAS-5 as the species of a combination; and the election of corticosteroids as the species of a further therapeutic ingredient to be administered in the method, in the reply filed on 15 May 2026, is acknowledged. Claims 1-6, 9-19 read on the elected species (dexamethasone of instant claims 14, 15, 16, 19 is a corticosteroid). Claims 7-8 are withdrawn, as being drawn to a non-elected species.
Since Applicant has set forth no arguments against the requirement of restriction/election, the election is treated as being made without traverse, and the restriction/election requirement is maintained and is herein made FINAL.
Claims 1-6, 9-19 have been examined to the extent they read on the elected species, and the following objections are rejections are made below.
Claim objection
Claims 7, 8, while currently withdrawn, are objected to because of the following informality: The withdrawn claims are objected to for being presented in a non-compliant form. Specifically, the status identifiers state the claims are “(Previously presented)”, but the claims are withdrawn because of the election made by the Applicant on 15 May 2026. As such, claims 7-8 should be identified as "(Withdrawn)" until such time as examiner rejoins the claims for examination. Appropriate correction is required. See MPEP 714(C).
Claim 1 is objected to because the recitation “ a method of treating […] in a subject” could read -- a method of treating […] in a subject in need thereof --.
Claim 5 is objected to because, for clarity, it should read -- The method of claim 1, wherein the inhibitor of SAM cycle enzyme is a S-adenosylhomocysteine hydrolase inhibitor selected from the group consisting of D-eritadenine (DER) and 3-deazaneplanocin A (DZNep), or a pharmaceutically acceptable salt thereof.--
Claim 6 is objected to because, for clarity, it should read -- The method of claim 1, wherein the inhibitor of SAM cycle enzyme is 3-deazaneplanocin A (DZNep), or a pharmaceutically acceptable salt thereof.—
(Alternatively, claim 6 could read -- The method of claim 5, wherein the S-adenosylhomocysteine hydrolase inhibitor is 3-deazaneplanocin A (DZNep), or a pharmaceutically acceptable salt thereof.--).
Similarly, claim 7 is objected to because, for clarity, it should read -- The method of claim 1, wherein the inhibitor of SAM cycle enzyme is a methionine adenosyltransferase inhibitor which is a fluorinated N,N-dialkylaminostilbene, or a pharmaceutically acceptable salt thereof. --
Claim 8 is objected to because, for clarity, it should read -- The method of claim 1, wherein the inhibitor of SAM cycle enzyme is a methionine adenosyltransferase inhibitor selected from the group consisting of FIDAS-5, MAT2A inhibitor 1 and PF-9366, or a pharmaceutically acceptable salt thereof. –
Claims 12, 13, 14, 15, 16, 19 are objected to because they recite “a further therapeutic ingredient”. The claims could recite –an additional therapeutic agent-- instead of “a further therapeutic ingredient”.
Claim 17 is objected to because the recitation “ a method of treating […] in a subject” could read -- a method of treating […] in a subject in need thereof --.
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 4 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 pre-AIA the applicant regards as the invention. Claim 4 is drawn to the method of claim 1, wherein inhibition of the at least one SAM cycle enzyme leads to decrease of the SAM concentration and/or increase of the
S-adenosylhomocysteine (SAH) concentration and/or decrease of the ratio of SAM/SAH.
It is unclear how the inhibition of SAM cycle enzyme leads to a decrease in concentration […]. It appears that administering a SAM cycle inhibitor to the subject results in certain levels/concentrations of SAM and SAH in the subject, measured in a biological sample (not disclosed).
Claim 4 recites “a decrease of the SAM concentration and/or increase of the
S-adenosylhomocysteine (SAH) concentration and/or decrease of the ratio of SAM/SAH”. It is unclear how the increase or decrease is to be measured, as the claim fails to establish a standard or threshold level. For example, the increase or decrease could be relative to another sample taken from the same subject previously, either before acquiring COVID-19 infection or after acquiring COVID-19. Alternatively, the increase or decrease could be relative to a healthy subject, i.e., a different subject than the subject currently afflicted with COVID-19. Further, the level of biomarker may vary over time in the same sample. Establishing an increase or decrease in certain biomarkers requires that a biological sample is compared to a predetermined standard level, yet the claim fails to clearly set forth whether this predetermined standard level is a standard established from a healthy subject, or from the same subject from a previously acquired sample. The examiner notes that a change in the levels of biomarkers could indicate disease progression, disease regression, or merely a diagnosis of the condition. Further, claim 4 fails to clarify what is the biological sample used for determining an increase or decrease in SAM or SAH. In other words, it appears that claim 4 is directed towards measuring levels of biological molecules in two different biological samples and comparing said levels between the two different biological samples to determine an increase and/or a decrease; however, the claim fails to clearly establish the origins of the two different biological samples, or the reference or standard by which one would make a comparison of levels of the one or more biological molecules. One wishing to practice the instantly claimed invention would thus not recognize the metes and bounds for which Applicant seeks protection.
For these reasons, the metes and bounds of the present claims cannot be determined and one having ordinary skill in the art would not necessarily be reasonably apprised of the scope of the claims.
Appropriate clarification/correction is required.
Claim 9 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 pre-AIA the applicant regards as the invention.
Regarding claim 9, the phrase "such as" (kidney injury such as proteinuria and acute kidney injury) 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).
Appropriate correction is required.
Claims 10, 11 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 pre-AIA the applicant regards as the invention. Claims 10 and 11 depend on claim 1 and recite that a combination of at least two inhibitors inhibiting two different SAM cycle enzymes is administered. Yet, claim 1 recites administering of an inhibitor of at least one S-adenosylmethionine (SAM) cycle enzyme, wherein the at least one SAM cycle enzyme is selected from the group consisting of S-adenosylhomocysteine hydrolase, methionine adenosyltransferase, betaine- homocysteine methyltransferase, methionine synthase and methionine synthase reductase. Claim 1, as written, recites administering one SAM inhibitor in the method, where said inhibitor inhibits at least one SAM cycle enzyme from the 5 listed in claim 1.
As such, there is insufficient antecedent basis for the limitation “a combination of at least two inhibitors inhibiting two different SAM cycle enzymes” of claims 10, 11, in claim 1.
Appropriate clarification of the claim language is required.
In the interest of compact prosecution, the examiner considers claim 1 to recite administering to the subject at least one inhibitor of S-adenosylmethionine (SAM) cycle enzyme, wherein the SAM cycle enzyme is selected from the group consisting of S-adenosylhomocysteine hydrolase, methionine adenosyltransferase, betaine- homocysteine methyltransferase, methionine synthase and methionine synthase reductase.
Claims 13, 15, 16 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 pre-AIA the applicant regards as the invention.
Claim 13 is drawn to a method of preventing or treating COVID-19 in a subject, or preventing or treating SARS-CoV-2 infection in a subject, the method comprising administering to the subject a pharmaceutical composition comprising the inhibitor of claim 1 together with a pharmaceutically acceptable carrier and an optionally further therapeutic ingredient. Claims 15, 16 depend on claim 13.
Claim 13 is unclear because it recites “the inhibitor of claim 1”, yet claim 1 is not drawn to an inhibitor, but rather to a method of treating COVID-19 in a subject in need thereof. As such, it is unclear what is being claimed in claim 13.
In the interest of compact prosecution, claim 13 is interpreted to be drawn to
A method of preventing or treating COVID-19 in a subject in need thereof, the method comprising administering to the subject a pharmaceutical composition comprising an inhibitor of S-adenosylmethionine (SAM) cycle enzyme, a pharmaceutically acceptable carrier and optionally an additional therapeutic agent,
wherein the SAM cycle enzyme is selected from the group consisting of S-adenosylhomocysteine hydrolase, methionine adenosyltransferase, betaine- homocysteine methyltransferase, methionine synthase and methionine synthase reductase.
Claims 14, 15 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 pre-AIA the applicant regards as the invention.
In claim 14, the phrase “selected from the group consisting of: (i) […], […], or interferons; or (ii)” is vague and indefinite because the term “or interferons; or (ii)” would mean that the claim is open ended in the closed Markush expression “selected from the group consisting of”.
The same analysis applies to claim 15.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 14 recites the broad recitation “nucleotide analogs”, and the claim also recites “remdesivir”, which are the narrower statements of the range/limitation.
Further, claim 14 recites the broad recitation “inhibitors of autophagy”, and the claim also recites “hydroxychloroquine”, which is the narrower statement of the range/limitation.
Further, claim 14 recites the broad recitation “ATK kinase inhibitor”, and the claim also recites “ipatasertib”, which is the narrower statement of the range/limitation.
Claim 14 recites the broad recitation “protease inhibitors”, and the claim also recites “marimastat, camostat”, which is the narrower statement of the range/limitation.
Claim 14 recites the broad recitation “corticosteroids”, and the claim also recites “dexamethasone”, which is the narrower statement of the range/limitation.
Claim 14 recites the broad recitation “interferons”, and the claim also recites “type I interferon”, which is the narrower statement of the range/limitation.
The same analysis applies to claim 15.
The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Appropriate correction is required.
Claim Rejections - 35 USC § 102
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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(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 1-6, 9, 12, 13, 17, 18 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Siddiqi (US2023/0302003, priority from U.S. provisional patent application 63/062,093, filed August 6, 2020, cited in PTO-892).
Sidiqqi teaches (U.S. provisional patent application 63/062,093, filed August 6, 2020, page 4, third paragraph and Table 1) a method of treating COVID-19 infection in a subject by administering to the subject an inhibitor of SAH hydrolase, as in instant claims 1, 3, which is 3-deazaneplanocin A (DZNep, Applicant’s elected species), as in instant claims 5, 6, 17.
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Sidiqqi teaches (U.S. provisional patent application 63/062,093, page 30, third paragraph) that the compounds of the invention may be administered conjointly with another therapeutic agent, as in instant claims 12, 13.
Sidiqqi teaches (U.S. provisional patent application 63/062,093, page 2, last paragraph, page 3, first paragraph) that many of the agents of the invention are directed towards RdRp, which is consistent with inhibiting virus replication, as in instant claims 2, 18.
Regarding claim 4, even though Sidiqqi does not specifically teach decreasing SAM concentration and/or increasing SAH concentration, the ability to decrease SAM concentration in a human patient upon administration, is an inherent property of the inhibitor of SAH hydrolase, 3-deazaneplanocin A (DZNep). In the instant case, decreasing SAM concentration is inherently associated with treatment of COVID-19 by administering SAH hydrolase inhibitor DZNep. Therefore, practicing the method of Sidiqqi would inherently practice the method herein claimed.
Since Sidiqqi teaches administration of the very therapeutic agent DZNep, to the very same patient population, patients suffering from COVID-19, to treat said patients, said therapeutic agent, upon administration, will elicit the same effect on the SAM and/or SAH levels in said patients.
Since Sidiqqi teaches administration of the very therapeutic agent DZNep, to the very same patient population, patients suffering from COVID-19, to treat said patients, said therapeutic agent, upon administration, will elicit the same effect on the virus replication in the respiratory system of the patient, as in instant claims 2, 18, or in preventing lung fibrosis in the patient, as in instant claim 9. The ability to inhibit viral replication in a patient upon administration, is an inherent property of the inhibitor of SAH hydrolase, 3-deazaneplanocin A (DZNep). In the instant case, inhibiting viral replication in the respiratory system of the patient is inherently associated with treatment of COVID-19 by administering SAH hydrolase inhibitor DZNep.
As such, a method of instant claims 1-6, 9, 12, 13, 17, 18 is anticipated by Sidiqqi.
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, 12-16, 19 are rejected under 35 U.S.C. 103 as being unpatentable over Siddiqi (US2023/0302003, priority from U.S. provisional patent application 63/062,093, filed August 6, 2020, cited in PTO-892), as applied to claim 1 above, in view of Ahmed et al. (Comprehensive Clinical Medicine 2020, 2, 2637-2646, cited in PTO-892).
Sidiqqi teaches (U.S. provisional patent application 63/062,093, filed August 6, 2020, page 4, third paragraph and Table 1) a method of treating COVID-19 infection in a subject by administering to the subject an inhibitor of SAH hydrolase, as in instant claims 1, 3, which is 3-deazaneplanocin A (DZNep, Applicant’s elected species), as in instant claims 5, 6, 17.
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Sidiqqi teaches (U.S. provisional patent application 63/062,093, page 30, third paragraph) that the compounds of the invention may be administered conjointly with another therapeutic agent, as in instant claims 12, 13.
Sidiqqi teaches (U.S. provisional patent application 63/062,093, page 2, last paragraph, page 3, first paragraph) that many of the agents of the invention are directed towards RdRp, which is consistent with inhibiting virus replication, as in instant claims 2, 18.
Regarding claim 4, even though Sidiqqi does not specifically teach decreasing SAM concentration and/or increasing SAH concentration, the ability to decrease SAM concentration in a human patient upon administration, is an inherent property of the inhibitor of SAH hydrolase, 3-deazaneplanocin A (DZNep). In the instant case, decreasing SAM concentration is inherently associated with treatment of COVID-19 by administering SAH hydrolase inhibitor DZNep. Therefore, practicing the method of Sidiqqi would inherently practice the method herein claimed.
Since Sidiqqi teaches administration of the very therapeutic agent DZNep, to the very same patient population, patients suffering from COVID-19, to treat said patients, said therapeutic agent, upon administration, will elicit the same effect on the SAM and/or SAH levels in said patients.
Sidiqqi does not teach administration of a combination of DZnep and corticosteroid dexamethasone, in a method of treating COVID-19, as in instant claims 12-16, 19.
Ahmed et al. (Comprehensive Clinical Medicine 2020, 2, 2637-2646) teach dexamethasone administered in a method of treating COVID-19.
It would have been obvious to a person of ordinary skill in the art to combine the teachings of Sidiqqi and Ahmed, and administer a combination of DZNep and dexamethasone to a subject suffering from COVID-19, in a method of treating COVID-19. The person of ordinary skill in the art would have been motivated to administer a combination of DZNep and dexamethasone to a COVID-19 patient, because each of DZNep and dexamethasone were known to be useful in treating COVID-19 patients, as taught by Sidiqqi and Ahmed. Therefore, one of ordinary skill in the art would have reasonably expected that combining DZNep and dexamethasone, known to be useful for the same purpose, i.e. treating COVID-19, in a method of treating COVID-19, would result in therapeutic effect. Since all compounds in the combination for administration herein are known to be useful to treat COVID-19, it is considered prima facie obvious to co-administer them in a method used for the same purpose. At least additive therapeutic effects would have been reasonably expected. See In re Kerkhoven, 205 USPQ 1069 (CCPA 1980).
As such, claims 1, 12-16, 19 are rejected as prima facie obvious.
CONCLUSION
Claims 1-6, 9-19 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to IRINA NEAGU whose telephone number is (571)270-5908. The examiner can normally be reached Mon-Fri 8-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JEFFREY 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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/IRINA NEAGU/Primary Examiner, Art Unit 1629
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