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/US2022/046750, filed 10/14/2022, which claims the priority benefit of PRO Application No. 63/255,998, filed 10/15/2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 04/30/2024, and 09/04/2025 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 1-14, 19-23, 25 and 27 are pending and currently under examination. Claims 9-14, 19-23 and 25 have been amended. Claims 15-18, 24, 26, and 28-40 have been cancelled by applicant without prejudice or disclaimer.
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.
Claims 20-23 and 27 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 20-23 recite the limitation "The method of claim 1" in line 1 of the claims wherein Claim 1 as written does not disclose a method of treating. There is insufficient antecedent basis for this limitation in the claim.
Claim 27 recites the limitation "[a] compound that is more hydrophilic than the compound of formula II that is convertible in vivo to the compound of formula II" in lines 1 and 2 of the claim. Formula II is not defined. There is insufficient antecedent basis for this limitation in the claim.
A skilled artisan would be unable to determine whether the compound more hydrophilic than the compound of formula II refers only to the compound of formula I of the instant claims or to other compounds more hydrophilic than the compound of formula II. This rejection may be overcome by deleting the claim, amending claim language to narrow the scope of compounds more hydrophilic than formula II or amending claim dependency to a compound of formula I of instant claim 1.
Claim Rejections - 35 USC § 102
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 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, 3 and 13 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Lu (WO 2021/037183 Al).
Lu discloses the structure of compound 22 (pg. 29) as a derivative of formula I which anticipates the structural limitations of formula I of the instant claims where X1 is N, X2 is CH2OCO(CH2)n2aCOOH wherein n2a is 2 and X3 is NH.
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Lu’s compound 22 (Left) Applicants formula I (Right)
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.
Claims 1, 3-5, 10, 12-14, 19-23 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Lu (WO 2021/037183 Al) in view of Jarrett (WO 2016/183296 A1) and further in view of Rini pgs. 175-180 (SU11248 and AG013736: Current Data and Future Trials in Renal Cell Carcinoma).
The instant claims are directed to a compound of formula I and a pharmaceutical composition (hydrogel) with an excipient administered as a treatment for a disease or condition of renal cell carcinoma (RCC), or ocular disease of diabetic retinopathy, AMD, DME, or RVO wherein the compound of formula I is converted in vivo to a compound of formula II.
Lu et al. teach the compounds of formula I used in pharmaceutical compositions for inhibiting or adjusting the activity of a tyrosine kinase, and treating tyrosine kinase-mediated disease symptoms or diseases including cancers (Abstract). Lu discloses the structure of compound 22 (pg. 29) as a derivative of formula I which satisfies the structural limitations of formula I of the instant claims where X1 is N, X2 is CH2OCO(CH2)n2aCOOH wherein n2a is 2 and X3 is NH. Lu also teaches R1, R2, and R3 of the reference formula I can be independently H or a protecting group (Google machine translation below of pg. 3, lines 29-31).
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Lu also teaches an embodiment wherein a compound of formula I is administered to a subject for the treatment of renal cell carcinoma (Google machine translation below of pg. 8, lines 9-15).
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Lu also discloses embodiments of formula I are prodrugs of axitinib which are metabolized or converted into axitinib in a subject (Google machine translation below of pg. 4, lines 1-5).
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However, Lu fails to teach the use of hydrogel in a pharmaceutical composition with a compound of formula I.
Jarrett et al teach drug delivery involving hydrogels for various medical conditions, and includes hydrogels formed in an eye with extended drug release times and an embodiment wherein a method of delivering a therapeutic agent to a tissue by forming a hydrogel in situ in an eye with a therapeutic agent dispersed in the hydrogel, the agent having a low solubility in water and wherein the agent may be essentially insoluble in water (Abstract). Jarrett teaches hydrogels may be formed in natural or surgical voids or potential spaces, including other sites where cancer has been removed or is located and include placement of the hydrogel material at a site of a cancer, for example, at a prostate for therapy of prostate cancer or breast cancer (pg. 11, lines 19-22). Jarrett also teaches example 8 which discloses the process of making and administering of axitinib and hydrogel to the eye of a subject with pharmaceutically acceptable excipients (pg. 55, lines 9-26.)
However, Jarrett fails to explicitly disclose axitinib as a treatment for renal cell carcinoma.
Rini et al teach several molecular pathways are implicated in renal cell carcinoma (RCC) pathogenesis, including the von Hippel-Lindau gene inactivation leading to vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) expression and that AG013736 (axitinib) is a small-molecule inhibitor of the tyrosine kinase portion of the VEGF and PDGF receptors with substantial clinical activity reported for this agent in metastatic RCC trials (Abstract). Rini also discloses Small molecule agents including AG013736, target the receptors for VEGF and PDGF ligands and have exhibited robust clinical activity in metastatic RCC (Conclusion, pg. 179).
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 formulate a prodrug of axitinib by attaching the disclosed protecting group R1 of CH2OCO(CH2)2COOH taught by Lu to the other disclosed protecting group locations of R1 and R3 in reference formula I for administration to a patient with RCC or an ocular disease using the axitinib hydrogel teachings of Jarrett and the disclosures of Rini of axitinib in treating RCC. See MPEP 2144.05 II and 2144.06.
A person of ordinary skill in the art would have been motivated to administer a derivative of formula I to a subject with renal cell carcinoma because Lu disclosed compound 22 as an axitinib prodrug suitable for treating renal cell carcinoma in a subject and would have had a reasonable expectation of success in treating renal cell carcinoma by administering compound 22 with Rini’s teaching of axitinib with Jarrett’s teaching of axitinib in a hydrogel to successfully treat a subject with RCC or an ocular disease.
Conclusion
Claims 2, 6-9, 11 are objected. All claims are rejected, no claims are allowed.
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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