DETAILED ACTION
Receipt is acknowledged of applicant’s Preliminary Amendment filed 1/16/2025.
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 3, 6-8, 12 and 13 have been amended. No claims were cancelled or newly added. Accordingly, claims 1-13 remain pending in the application and are currently under examination.
Information Disclosure Statement
The IDS’s filed 2/26/2025, 3/4/2025, 3/11/2025, 11/28/2025, 1/30/2026 and 7/15/2026 have been considered. Signed copies are enclosed herewith.
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 6-13 are rejected under 35 U.S.C. 103 as being unpatentable over Hattori et al. (WO 2019/098393 A1, May 23, 2019, machine translation, hereafter as “Hattori”) as evidenced by PubChem (see PTO-892).
The instant claims are drawn to a hyaluronic acid derivative pharmaceutical composition comprising: an active ingredient suspended in an aqueous carrier containing a hyaluronic acid derivative, wherein the active ingredient is a fine particle having a molecular weight of 100 g/mol or greater and 8000 g/mol or less.
Regarding instant claims 1, 2 and 6-13, Hattori teaches a pharmaceutical composition containing a hyaluronic acid derivative containing one or more repeating units represented by formula (Ia), formula (Ib), and formula (Ic), wherein R5y in formula (Ib) is a (C1-6 alkyl) carbonyl group, and Z3 is a steryl group (claims 1, 6, and 15). Hattori also indicates that: the (C1-6 alkyl) carbonyl group is, for example, an acetyl group (page 13, 1st para.); the steryl group is, for example, cholesterol (page 14, 2nd para.); in a pharmaceutical composition for use in transmucosal administration, containing a drug and a hyaluronic acid derivative, particles obtained by finely pulverizing a drug are coated with the hyaluronic acid derivative of the present invention (page 15, 3rd para.; page 41, 5th-6th para.); the hyaluronic acid derivative precipitates at physiological saline concentration (page 35, 5th para.); the drug is an immunosuppressive agent such as cyclosporin (page 42, 7th para.; Example 14-3); and the pharmaceutical composition is administered as eye drops or by injection (page 15, 3rd para.; para. bridging pages 41-42; page 42, 4th para.). It is noted that cyclosporin has a molecular weight of 1202.6 g/mol, is poorly water-soluble and a cyclic peptide containing 11 amino acids one of which is D-alanine (an unnatural amino acid) and 8 different kinds of amino acids (MeBmt, Abu, Sar, MeLeu, Val, Ala, D-Ala and MeVal) as evidenced by PubChem. Hattori teaches that the hyaluronic acid derivative can be used as a carrier for an active ingredient/drug in an aqueous solution (para. bridging pages 35-36). Hattori further teaches suspensions (page 41, 5th para.). Hattori teaches grinding to produce a powder as well as nanoparticles and microparticles (page 35, 2nd para.; page 41, 5th para.; Examples). It is noted that the instant claims are product claims and any intended use recitation such as “wherein the hyaluronic acid derivative pharmaceutical composition is administered subcutaneously, intramuscularly...” in claim 12 or “wherein an administration method is injection, eye drop, or application” in claim 13 does not alone show patentable distinction. A recitation of intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. In other words, if the prior art structure is capable of performing the intended use, then it meets the claim.
While Hattori does not teach all of the elements in a single embodiment, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the individual components with a reasonable expectation of success because Hattori teaches each of the elements as being suitable for the invention.
Thus, the teachings of Hattori render the instant claims prima facie obvious.
Claims 3-5 are rejected under 35 U.S.C. 103 as being unpatentable over Hattori et al. (WO 2019/098393 A1, May 23, 2019, machine translation, hereafter as “Hattori”) as evidenced by PubChem (see PTO-892), as applied to claims 1 above, and further in view of Akiyoshi et al. (WO 2010/053140 A1, May 14, 2010, machine translation, hereafter as “Akiyoshi”).
Hattori teaches the elements discussed above.
Hattori is silent to the particular hyaluronic acid derivative of Formula (I) (claim 3), wherein R represents a hydrophobic group (claim 4), wherein the hydrophobic group is a cholesteryl group (claim 5).
Akiyoshi teaches a hyaluronic acid derivative into which a hydrophobic group is introduced. The hyaluronic acid derivative contains one or more repeating units represented by Formula (I):
PNG
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234
528
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wherein R1, R2, R3, and R4 are each independently selected from a hydrogen atom, C1-6 alkyl, formyl, and C1-6 alkylcarbonyl; Z represents a direct bond or a peptide linker consisting of 2 to 30 arbitrary amino acid residues; X1 has the following formula -NRb-R, -NRb-COO-R, -NRb-CO-R, -NRb-CO-NRc-R, -COO-R, -O-COO-R, -S-R, -CO-Ya-S-R, -O-CO-Yb-S-R, -NRb-CO-Yb-S-R, and -S-S-R; a hydrophobic group represented by Ra, Rb and Rc are each independently selected from a hydrogen atom, C1-20 alkyl, amino C2-20 alkyl and hydroxy C2-20 alkyl, wherein the alkyl portion of the group is 1-3 groups selected from -O- and -NRf- may be inserted; Rf is selected from a hydrogen atom, C1-12 alkyl, amino C2-12 alkyl, and hydroxy C2-12 alkyl, wherein the alkyl portion of the group is 1-2 selected from -O- and -NH- groups may be inserted; R is a steryl group; Y is C2-30 alkylene, or -(CH2CH2O)m-CH2CH2-, wherein the alkylene is from -O-, -NRg-, and -S-S- 1 to 5 groups of choice may be inserted; Rg is selected from a hydrogen atom, C1-20 alkyl, amino C2-20 alkyl or hydroxy C2-20 alkyl, wherein the alkyl portion of the group is 1-3 selected from -O- and -NH- groups may be inserted; Ya is C1-5 alkylene; Yb is C2-8 alkylene or C2-8 alkenylene; m is an integer selected from 1 to 100 (abstract; claim 1). Akiyoshi teaches
that a drug can be efficiently encapsulated by the hyaluronic acid derivative and that the hyaluronic acid derivative aggregates and forms a precipitate at a physiological salt concentration (page 19, 4th para.). In addition, Akiyoshi teaches specifically that hyaluronic acid which contains an acetyl group having hyaluronic acid and has a cholesteryl group introduced therein was synthesized, and the formation of a precipitate was confirmed for a compound that was complexed with a drug, and that pharmacokinetics in vivo was confirmed (Examples – pages 28-54).
In the invention described in Hattori, it is suggested that R5y can be an acetyl group and Z3 can be a cholesteryl group. In addition, in Akiyoshi, which shares with the invention disclosed in Hattori the feature of being a hyaluronic acid derivative that can form a precipitate at a physiological salt concentration and be complexed with a drug, formation of a precipitate and pharmacokinetics are confirmed for a specific structure having an acetyl group and a cholesteryl group. This being the case, a person skilled in the art could easily have selected a structure in which R5y is an acetyl group and Z3 is a cholesteryl group in formula (Ib) of the invention disclosed in Hattori with reference to the disclosures in Akiyoshi. Thus, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include the particular hyaluronic acid derivatives of instant claims 3-5 into Hattori, as suggested by Akiyoshi, with a reasonable expectation of success.
The combined teachings of Hattori and Akiyoshi render the instant claims prima facie obvious.
Conclusion
All claims have been rejected; no claims are allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CASEY HAGOPIAN whose telephone number is (571)272-6097. The examiner can normally be reached on M-F 9:00 am - 5:00 pm.
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/CASEY S HAGOPIAN/Examiner, Art Unit 1617
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