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 is a national stage application under 35 U.S.C. § 371 of International Application No. PCT/EP2021/058240, filed 03/30/2021, which claims the priority benefit of European Patent Application No. 20167256.5, filed 03/31/2020 and European Patent Application No. 21163417.5, filed 03/18/2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 01/27/2023, 10/03/2023,
11/09/2023, 12/14/2023, 02/06/2024, 03/04/2024, 05/29/2024, 08/22/2024, 02/19/2025, 05/19/2025, 08/27/2025, and 04/08/2026 were filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Status of claims
Claims 11-112, and 115-12 are pending in this application. Claims 106-107 and 115 have been withdrawn. Claims 11, 101, 105-109, 111-112 and 115-118 have been amended. Claims 1-98 and 113-114 have been cancelled by applicant without prejudice or disclaimer. Claims 99-105, 108-112, and 116-121 are currently under examination.
Applicant’s arguments, filed 04/22/2026, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. They constitute the complete set presently being applied to the instant application.
The obviousness rejection below is repeated from the 01/27/2026 Office Action and modified in order to address the most recent amendments.
Claim Rejections - 35 USC § 103
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claim 99-104, 108-112 and 118 are rejected under 35 U.S.C. 103 as being unpatentable over Boman (U.S. PAT. 8,058,306 B2) in view of Davis (WO 2019/005898 Al).
The instant claims are directed to a method of treating a viral disease or disorder with pulmonary insufficiency, comprising administering to a subject in need a therapeutically effective amount of a compound of formula (I) ({3-[ 1-(2-nitrophenyl)-1H-pyrrol-2-yl]-allylidene}-aminoguanidine).
Boman et al. teaches a phenyl pyrrole aminoguanidine acetate derivative of general formula I as compound 19, {3-[ 1-(2-nitrophenyl)-lH-pyrrol-2-yl ]-allylidene}amino guanidinium, CAS registry number 959850-73-8, "shows the synthetic route to compound 2 of the invention, [1-(2-Nitrophenyl)-IH-pyrrol-2-yl-allylideneamino ]guanidinium acetate (see FIG. ID, structure no. 19)." [sic] (col. 3, lines 65-66). Boman also teaches "In a further aspect the present invention relates to a pharmaceutical composition comprising a compound of the invention and a pharmaceutically acceptable carrier or excipient." (col. 3, lines 26-30). Boman teaches administration of a compound of formula I for the treatment of a systemic disease including inflammatory diseases and central nervous system diseases related to inflammation including viral infections (col. 21, lines 3-31). See MPEP 2131. Boman also discloses Included in the invention is also the administration of a compound of formula (I) or a pharmacologically acceptable salt thereof for the treatment of diseases related to inflammation in the lung and/or airways, such acute, chronic or subchronic inflammation in the lung and/or airway, upper and lower airway diseases such as chronic obstructive pulmonary disease (COPD), exacerbations in COPD, and acute respiratory diseases and/or chronic and/or subchronic airway and lung diseases. (col. 21, line 58-col. 22, line 5) Boman also teaches that compounds of the invention may be converted to their active acid addition salts with organic acids including acetic acid (col. 11, lines 26-32). Boman also discloses that the compounds of the invention are agonists or antagonists capable of binding to MC receptors MC1 and MC3 ( col. 18, lines 9-15). Boman also discloses that administration of a compound of formula I is used for the treatment of inflammation related to any origin including inflammation caused by a virus including AIDS (col. 23, lines 17-23). Boman also teaches treatments to inhibit acute renal failure in example 9 (col. 35, lines 6-20 and example 9, col. 36). Boman teaches that compounds of formula I are useful for the treatment of inflammation related to interleukin 6 ( col. 19 line 56 - col. 20 line 3). Boman discloses compound 2 is widely distributed to tissues (col. 46, lines 49- 57). Boman also teaches example 12 wherein compounds of the invention are administered via oral gavage, intravenous and subcutaneous injection once or twice daily (col. 39, lines 57-62).
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123
625
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(Boman' s compound 19)
However, Boman et al. fail to explicitly disclose a method of treating viral disease or disorder with pulmonary insufficiency by administering a compound of formula I.
Davis et al. teach Compositions and methods for treating chronic obstructive pulmonary disease (COPD) (abstract). Davis also teaches that emphysema and chronic bronchitis, which can be present to varying degrees in individual patients, are the hallmarks of COPD and together result in restriction of airflow, mild hypoxemia, frequent and often productive coughing, and exercise intolerance. Current therapeutic options are limited, and primarily ameliorate symptoms rather than prevent or reverse disease progression and that patients with COPD frequently require supplemental oxygen (usually delivered via nasal cannula) (pg. 1, lines 16-24).
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art, prior to the effective filing date of the instant application, to use Boman' s compound 19 to treat a viral disease or disorder by daily administration to a subject in need thereof because Boman disclosed the use of phenyl pyrrole aminoguanidine derivatives for the treatment of diseases associated with the melanocortin receptors which are related to inflammation and further disclosed the mean concentration in plasma following intravenous administration, intravenous pharmacokinetics, and oral bioavailability of compound 19 in example 13, figures ID, 2, 7, and 10 including a synthesis scheme in example I using acetic acid. A skilled artisan would have been motivated to select structure 19 for administration to a subject with a viral disease or disorder at least once daily due to a combination of an already disclosed synthesis scheme of structure 19, available plasma concentration data from administration to subjects and disclosure that compound 2 is widely distributed to tissues. Furthermore, as disclosed by Davis, a skilled artisan would have recognized that COPD is a disorder with pulmonary insufficiency for which supplementary oxygen is administered. See MPEP 2144.06.
Examiner notes Boman's compound of {3-[1-(2-nitrophenyl)-lH-pyrrol-2-yl]-allylidene} -aminoguanidinium, taught as structure 19 satisfies the structural limitations of formula I of the instant claims where R1 is NO2, R2-R7 is H, n is 1.
A person of ordinary skill in the art would have been motivated to select the compound of structure 19, for use in a pharmaceutical composition for daily administration to a subject with a viral disease or disorder because of the disclosures of Boman regarding wide systemic distribution into tissues by structure 19 and the teachings that positive effects seen where inflammation is caused by viral infection. A person of ordinary skill would have further been motivated to use Boman' s teachings of structure 19 because of the ability of compound 2 (structure 19) to become widely distributed into tissues and therefore would have given the skilled artisan a reasonable expectation of success in treating systemic inflammation caused by viruses.
Allowable Subject Matter
Claims 105, 116-117, and 119 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter: Applicants method of treating viral pneumonia caused by influenza and acute respiratory distress syndrome (ARDS) caused by influenza virus or symptomatic COVID-19, including symptomatic COVID-19 with pulmonary insufficiency including pneumonia and ARDS by administering an effective amount of compound of (E)-N-trans-{3-[1-(2-nitrophenyl)-lH-pyrrol-2-yl]-allylidene} aminoguanidinium acetate (APl189) to a subject in need thereof makes a contribution over the closest prior art of record of Boman (U.S. PAT. 8,058,306 B2). Boman does disclose the use of applicants compound of (E)-N-trans-{ 3-[1-(2-nitrophenyl)-lH-pyrrol-2-yl ]-allylidene}amino guanidinium acetate (APl189), but the disclosures do not fairly teach or suggest to a person of ordinary skill a method of treating viral pneumonia caused by influenza or acute respiratory distress syndrome (ARDS) caused by influenza virus or symptomatic COVID-19 with applicants disclosed compound of (E)-N-trans-{3-[1-(2-nitrophenyl)-lH-pyrrol-2-yl]-allylidene} aminoguanidinium acetate (APl189) and therefore instant claims 120-121 are free of the prior art.
Response to Arguments
Applicant's arguments filed 04/22/2026 have been fully considered but they are not persuasive.
Applicant argues Boman does not disclose viral disease with pulmonary insufficiency or influenza with pulmonary insufficiency, and provides no data on viral diseases with pulmonary insufficiency.
Examiner agrees, however, the limitations of amended instant claim 99 as written also includes “…or disorders with pulmonary insufficiency…” which is defined by the specification of the disclosure as “[i]n one embodiment said pulmonary insufficiency is defined as a need for supplementary oxygen to maintain normal saturation.” (Specification pg. 19, lines 23-24). A person of ordinary skill would have therefore found it prima facie obvious that Boman’s disclosure of the lung disorder of COPD would include treatment with supplemental administration of oxygen to a subject when combined with Davis’s teaching that patients with COPD frequently require supplemental oxygen (usually delivered via nasal cannula).
Conclusion
Claims 99-104, 108-112 and 118 are rejected, claims 105, 116-117, and 119 are objected to, claims 120-121 are allowable.
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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERNESTO VALLE JR whose telephone number is (703)756-5356. The examiner can normally be reached 0730-1700 M-F EST, 1st Friday off.
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/E.V./Examiner, Art Unit 1623
/SAMANTHA L SHTERENGARTS/Primary Examiner, Art Unit 1623
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