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 .
Benefit of Earlier Filing Date
The instant application, filed 20 September 2024, claims the benefit of an earlier filing date to U.S. Provisional Patent Application Serial No. 63/584,402, filed 21 September 2023. Acknowledgment is made of Applicant’s claim.
Restriction/Election
Requirement for Restriction/Election was mailed 07 July 2026.
Applicant’s Response to Requirement for Restriction/Election was received 09 July 2026.
Applicant’s election without traverse of Group II (Claims 10-20) in the Response filed 09 July 2026 is acknowledged. The claims in Group I (Claims 1-9) are withdrawn.
Status of the Claims
The listing of claims filed 09 July 2026 has been examined.
Claims 1-20 are pending.
Claim 5 is amended.
Claims 1-9 are withdrawn.
Information Disclosure Statement
The Information Disclosure Statement (IDS) filed on 20 September 2024 is acknowledged and has been considered. Any lined-through references have not been considered and must be submitted or resubmitted in proper format for consideration. Specifically, NPL documents entitled “The Science and Practice of Pharmacy, A. Gennaro, ed., 20th edition, Lippincott, Williams & Wilkins, Philadelphia, PA.” as well as “Takada et al, “Encyclopedia of Controlled Drug Delivery,” Vol. 2, Mathiowitz ed., Wiley, 1999” are missing.
Specification
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because it contains a phrase which can be implied, specifically, “The present disclosure relates to…” A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Objections
Claims 10-11 and 14-18 objected to because of the following informalities:
Claim 10 recites, “…an effective amount the compound of claim 1.” This appears to be a typographical error. Examiner suggests amending to, “…an effective amount of the compound of claim 1,” or similar.
Claim 11 recites, “…an effective amount the compound of any one of claim 1.” This appears to be a typographical error. Examiner suggests amending to, “…an effective amount of the compound of claim 1,” or similar.
Claims 14 and 18 recite, “…wherein the compound inhibits protease.” This appears to be a typographical error. Examiner suggests amending to, “…wherein the compound inhibits a protease,” or similar.
Appropriate correction is requested.
In order to expedite prosecution, Applicant should be aware that withdrawn claim 1 shows a relatively low-resolution structure of a compound of Formula III and a clearer image of this structure should be provided.
Claim Rejections - 35 USC § 112(b)
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 13 and 17 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.
Claims 13 and 17 recite the limitation "the composition." There is insufficient antecedent basis for this limitation in the claim.
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, 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 10-12, 14, and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Al-Horani (Al-Horani et al., “Sulfonated Nonsaccharide Heparin Mimetics Are Potent and Noncompetitive Inhibitors of Human Neutrophil Elastase,” ACS Omega 2021, 6, 12699-12710).
Regarding claims 10-12, 14, and 18, Al-Horani teaches compounds of Formulas I-III (p. 12700, Fig. 2, Inhibitors 6-8), shown below:
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Inhibitors 7, 8, and 6 are structurally identical to the instantly recited compounds of Formula I, Formula II, and Formula III, respectively, except in Inhibitors 6-8 the sulfonic acid groups are unprotonated. Inhibitors 6-8 are sulfonated diphenyl-urea derivatives (p. 12701, Col. 2, 2.1. Direct Inhibition of HNE by Sulfonated Nonsaccharide Heparin Mimetics) which inhibit human neutrophil elastase (HNE), a serine protease involved in inflammation and in the innate immune response (p. 12699, Abstract). Al-Horani states, “…uncontrolled HNE activity may lead to severe cardiopulmonary diseases including chronic obstructive pulmonary disease, cystic fibrosis, bronchiectasis, acute lung injury, acute respiratory distress syndrome, pulmonary arterial hypertension, and idiopathic pulmonary fibrosis. Furthermore, several studies have provided significant evidence establishing the contribution of HNE to psoriasis and inflammatory skin disease, rheumatoid arthritis, the development and the progression of cancer, type-1 diabetes, [and] neuropathic pain…” (p. 12699, Col. 2). Inhibitor 7 demonstrated “significant [HNE] inhibition” and inhibitors having a globular structure, like Inhibitors 7 and 8, showed superior inhibition potency compared to their linear counterparts (p. 12702, Col. 1 & Fig. 8)
Al-Horani does not explicitly teach a method for treating inflammation or an inflammatory disease by administering an effective amount of compounds of Formulas I-III.
Prior to the filing of the instant application, a person having ordinary skill in the art (PHOSITA) following the teachings of Al-Horani would have found it prima facie obvious to treat inflammation or an inflammatory disease by administering an effective amount of compounds of Formulas I-III because Al-Horani discloses said compounds are HNE inhibitors, HNE being a protease which promotes inflammation. The instant Specification defines “effective amount” broadly, stating it is, “…the amount of an agent, e.g., a compound… that, when administered to a patient for treating a disease, is sufficient to affect such treatment for the disease.” (p. 8, ¶ [0045]). Thus, a PHOSITA would have been motivated to try using said HNE inhibitors in the treatment of inflammatory conditions, since Al-Horani indicates excessive HNE activity is linked to various inflammatory diseases, and would have known to optimize the amount of inhibitor administered based on the desired anti-inflammatory effect and guided by the IC50 values reported by Al-Horani.
Claims 15-16 and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Al-Horani (Al-Horani et al., “Sulfonated Nonsaccharide Heparin Mimetics Are Potent and Noncompetitive Inhibitors of Human Neutrophil Elastase,” ACS Omega, 2021, 6, 12699-12710) as evidenced by Ledoux (Ledoux et al., “Heparin-like dextran derivatives as well as glycosaminoglycans inhibit the enzymatic activity of human cathepsin G,” FEBS Letters, 2003, 537, 23-29).
Regarding claims 15-16 and 19-20, Al-Horani teaches all of the claimed elements as stated above. Furthermore, Al-Horani discloses Inhibitor 3, a sulfonated nonsaccharide heparin mimetic which is a sulfonated diphenyl-urea derivative, like Inhibitors 6-8 (p. 12700, Fig. 2), and selects Inhibitor 3 as a lead compound, suggesting it can be developed further, “…as a treatment for HNE-related cardiopulmonary and inflammatory diseases.” (p. 12705, 3. Conclusions). Additionally, Al-Horani identifies Inhibitor 3 as a cathepsin G (CatG) inhibitor as well as an HNE inhibitor (p. 12704, Fig. 7). Inhibitor 3 potently inhibits CatG, which is another serine protease involved in inflammation (p. 12703, Col. 2, 2.5 Selectivity Studies: Inhibition of Inflammatory, Digestive, and Fibrinolysis Serine Proteases by Molecule 3).
Al-Horani does not explicitly teach compounds of Formulas I-III are CatG inhibitors.
Prior to the filing of the instant application, a person having ordinary skill in the art (PHOSITA) following the teachings of Al-Horani would have found it prima facie obvious to try using compounds of Formulas I-III as inhibitors of CatG-mediated laminin and fibronectin degradation because Al-Horani discloses Inhibitor 3 is a CatG inhibitor. Inhibitor 3 is structurally similar to compounds of Formulas I-III and is a sulfonated diphenyl-urea derivative, also like compounds of Formula I-III. Thus, a PHOSITA would have had a reasonable expectation of success in using compounds of Formulas I-III as CatG inhibitors as CatG and HNE, both being serine proteases, have related tertiary structures and Inhibitor 3 acts as both a CatG and an HNE inhibitor. Furthermore, as evidenced by Ledoux, CatG inhibitors, specifically heparin/heparin sulfate mimics, inhibit CatG-mediated fibronectin and laminin degradation (p. 23, Abstract). Thus, a skilled artisan could have predicted administering a CatG inhibitor would attenuate CatG-mediated fibronectin and laminin degradation.
Claims 13 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Al-Horani (Al-Horani et al., “Sulfonated Nonsaccharide Heparin Mimetics Are Potent and Noncompetitive Inhibitors of Human Neutrophil Elastase,” ACS Omega, 2021, 6, 12699-12710) in view of Gupta (Gupta et al., "Understanding the routes of administration" Handbook of Space Pharmaceuticals. Cham: Springer International Publishing, 2022, 23-47)
Regarding claims 13 and 17, Al-Horani teaches all of the claimed elements as stated above.
Al-Horani does not explicitly disclose specific administration routes.
Prior to the filing of the instant application, a person having ordinary skill in the art (PHOSITA) following the teachings of Al-Horani would have found it prima facie obvious to prepare a composition comprising a compound of Formulas I-III and formulate said composition for various administration routes, such as for subcutaneous or oral administration, because, as evidenced by Gupta, such administration routes are well-known in the art. Gupta states, “In order for a drug to produce its intended therapeutic actions, it must first be able to reach its target site of action in the body at an appropriate concentration… There are advantages and disadvantages associated with each route of administration.” (p. 24, ¶ 2; p. 25, Table 1). For example, a PHOSITA would understand administering pharmaceutical compositions orally is generally the most convenient administration route, but administering compositions by intravenous (IV) injection results in superior bioavailability. Thus, a skilled artisan would have known to choose an administration route based on its unique advantages and disadvantages, the drug’s site of action, and the drug’s pharmacokinetic/pharmacokinetic properties.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRIANNA L BAUER whose telephone number is (571)272-5752. The examiner can normally be reached 8am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, ADAM C MILLIGAN can be reached at (571)270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/B.L.B./Examiner, Art Unit 1623
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
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