DETAILED ACTION
Status of Application
Receipt of the response to Notice of Non-Compliant Amendment, the amendments to the claims and the applicant arguments/remarks, filed on 03/31/2026, is acknowledged. Amendments to the specification, filed 12/22/2025, have not been entered, because the replacements are not clearly delineated.
Claims 1-2, 4-12, 14-20, filed 03/31/2026, are pending in this action. Claims 3, 13 have been cancelled. Claims 1-2, 4-12, 14-20 have been amended. Claims 1-2, 4-12, 14-20 are currently under consideration.
Any rejection or objection not reiterated in this action is withdrawn. Applicant's amendments necessitated new ground(s) of objection and/or rejection presented in this office action.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . 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 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.
Priority
This application, filed February 20, 2025, claims benefit of provisional U.S. Application No. 63/556,256, filed February 21, 2024.
Specification
The lengthy specification (57 pages, exclusive of claims) has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification. MPEP 608.01. The specification is objected to because of the following informalities:
The specification comprises typographic errors, e.g., “Methacrylate Hyaluronic Acid (MHA) polymer” (e.g., Para. 0055, 0097), “glucose—liquid” (e.g., Para. 0085), “Lithium phenyl-“ (Para. 0098) that need to be corrected to “methacrylate hyaluronic acid (MHA) polymer”, “glycose liquid”, “lithium-phenyl-“, respectively, or clarified. Appropriate correction is required.
The specification comprises acronyms without proper definition (e.g., Para. 0050, 00111, 00120, 00122). The acronym should be given once in parenthesis after the first use of the full term (e.g., ultraviolet (UV)) and then the acronym is used alone thereafter if needed. Appropriate correction is required.
The use of the trademarks/trade names has been noted in this application (e.g., Para. 0103, 0109). Although the use of trademarks/trade names is permissible in patent applications, the proprietary nature of the trademarks/trade names should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as trademarks. The use of language such as “the product X (a descriptive name) commonly known as Y (trademark)” is not permissible since such language does not bring out the fact that the latter is a trademark. Language such as “the product X (a descriptive name) sold under the trademark Y” is permissible. MPEP §608.01(v). Further, it is noted that the trademarks/trade names are used to identify a source of goods, and not the goods themselves. The formula or characteristics of the product may change from time to time and yet it may continue to be sold under the same trademark/trade name. Thus, a trademark/trade name does not identify or describe the goods associated with the trademark/trade name. Appropriate correction is required.
The title “T Particulate Calculation” recited on page 45 should be corrected to “Testosterone Particulate Calculation” for clarity. Similar is applied to pages 46, 48, 49. Appropriate correction is required.
Drawings
The drawings, filed 02/20/2025, are objected to because in Figs, 17A, 17B, 18 the size scales (bottom right) are not clearly identified. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Information Disclosure Statement
The information disclosure statements, filed 01/05/2026 and 03/31/2026, are acknowledged and have been considered. Please see the attached initialed PTO-1449.
Foreign language references listed in the information disclosure statement(s), for which no English translation has been provided, have not been considered. If an English abstract has been provided or available for a foreign language document then only the English abstract has been considered.
The information disclosure statement fails to comply with 37 CFR 1.98(b)(5), which requires that each publication listed in an information disclosure statement must be identified by publisher, author (if any), title, relevant pages of the publication, date, and place of publication. MPEP 609.05(a). In the present case, the examiner has considered all references filed by the applicant to expedite the prosecution. However, the applicant is informed that the references filed in an improper format (lined through) should be resubmitted in a proper format to be printed in the patent. MPEP 1302.12.
Claim Objections
Claims 1-2, 4-12, 14-20 are objected to because of the following informalities:
Claim 1 introduces the acronym “MHA” multiple times. To this point, it is noted that the acronym should be given once in parenthesis after the first use of the full term, and then the acronym is used alone thereafter if needed. Similar is applied to claims 2 and 11.
Claim1 recites the limitation “at least one (1) week” that should be corrected to “at least one week”. Similar is applied to claim 11.
Claim 4 comprises the typographic error “method of claim 2 wherein” that needs to be corrected to “method of claim 2, wherein”. Similar is applied to claims 5-10, 12, 14-20.
Appropriate correction is required.
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 1-2, 4-12, 14-20 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.
Newly amended claim 1 recites the limitation “irradiating the plurality of core-shell microparticles with ultraviolet light to crosslink the methacrylated hyaluronic acid (MHA) polymer in the liquid core” that is unclear, because the crosslinking step is not clearly delineated. First, as stated previously, it is unclear how one can apply UV light to a particular compound (i.e., MHA) in a multi-component system/solution. Second, it is unclear how and what constituents should be crosslinked – MHA monomers, OR this also includes a crosslinker? As best understood, the precursor core is crosslinked by activation of a photoinitiator with UV radiation, i.e., lithium phenyl-2,4,6-trimethylbenzoylphosphinate (see instant specification, Para. 0095, 0098, 0117). Similar is applied to claim 11. Clarification is required.
Newly amended claim 4 (dependent on claims 1, 2) recites the limitation “wherein the at least one non-alginate polymer is selected from the group consisting of non-alginate polysaccharide, hyaluronic acid, modified hyaluronic acid, collagen, gelatin, polyethylene glycol, chitosan, agarose, and combinations thereof” that is not reasonably clear. To this point, it is noted that independent claim 1 discloses the use of “methacrylated hyaluronic acid”, i.e., modified hyaluronic acid. Therefore, the scope of claim 4 is not clearly deliniated. Similar is applied to claim 14. Clarification is required.
Newly amended claim 9 (dependent on claim 1) recites the limitation “each hydrogel microparticle has a surface-to-surface dimension (maximum linear distance between opposing outer surfaces of the hydrogel microparticle) of less than 2 mm” that is unclear. First, it is noted that parenthetical expressions are not permissible, which do not contribute to clearness or exactness in stating applicant’s invention (Ex parte Cahill, 1893 C. D., 78; 63 O. G., 2125). In the present case, the instant specification defines the term “surface-to-surface” as “the measurement of the linear distance between two points on the droplet's surface opposite one another” (Specification, Para. 0074). No information regarding “maximum linear distance” is provided. Clarification is required. Second, it is noted that where a claimed value (i.e., microparticle size) varies with its method of measurement and several alternative methods of measurement are available, the value is indefinite when the claim fails to concurrently recite the method of measurement used to obtain it. Honeywell Intl. v. Intl. Trade Commn., 341 F.3d 1332, 1340 (Fed. Cir. 2003). It is well known in the field that there is no a comprehensive standard for particle size measurements, and different methods of particle size analysis yield different estimates of (micro)particle size for the same sample (see Wikipedia and references cited wherein), i.e., experimental estimates of (micro)particle sizes depend on methods of measurements used to obtain it. Third, it is unclear what particle size should be measured – radius, diameter. Without knowing these parameters, the metes and bounds of the claimed subject matter cannot be determined. Similar is applied to claim 10, 19, 20. Clarification is required
Claims 2, 5-8, 12-18 are rejected as being dependent on rejected independent claims 1 and 11 and failing to cure the defect.
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.
Claims 1-2, 4-12, 14-20 are rejected under 35 U.S.C. 103 as being unpatentable over Ramachandran et al., US 2015/0352056 A1 (hereinafter referred to as Ramachandran), in view of Ott et al., US 2022/0233454 A1 (hereinafter referred to as Ott), and further in view of Grover et al., US 2022/0175672 (cited in IDS; hereinafter referred to as Glover).
Ramachandran teaches method of encapsulating biological material in a 3-dimensional hydrogel matrix, wherein said method comprises (Claim 1; Title, Para. 0007, 0020, 0025 as applied to claims 1, 11):
(i) providing a hydrogel precursor solution that comprises a hydrogel precursor compound, a biological material, and a divalent cation selected from the group consisting of calcium, barium, strontium, and combinations thereof, dispersed or dissolved in a solvent system;
(ii) combining said hydrogel precursor solution with alginate to yield core/shell microparticles comprising an alginate shell and a liquid core comprising the hydrogel precursor solution;
(iii) crosslinking the hydrogel precursor compound in the liquid core to yield core/shell crosslinked microparticles, wherein each of the core/shell crosslinked microparticles comprises the alginate shell and a core comprising a 3-dimensional hydrogel matrix and the biological material suspended, encapsulated/entrapped in the hydrogel matrix;
(iv) removing the temporary alginate shell to yield self-sustaining hydrogel microbeads, each comprising the 3-dimensional hydrogel matrix and biological material entrapped therein.
Ramachandran teaches the use of such crosslinkable hydrogel precursor compounds as non-alginate copolymers, e.g., modified hyaluronic acid, collagen, gelatin, polyethylene glycol, chitosan, agarose (Para. 0019 as applied to claims 1, 2, 4, 11, 14).
Ramachandran teaches that the hydrogel precursor may also include additional ingredients such as fibronectin, laminin, collagen, other components of the extracellular matrix, and the like, including synthetic versions thereof (Claim 4; Para. 0015 as applied to claims 5, 15); photo-initiated crosslinkers, thermal-initiated crosslinkers, chemical crosslinkers (Para. 0027, 0028 as applied to claims 1, 11, 12).
Ramachandran teaches the use of sodium alginate bath (Claim 9; Para. 0024 as applied to claims 1, 6, 11, 16).
Ramachandran teaches that the alginate shell is removed by using a chelating agent, e.g., citrate, ethylene diamine tetraacetic acid (EDTA), ethylene glycol tetraacetic acid (EGTA), phosphates (Claim 17; Para. 0031 as applied to claims 7, 8, 17, 18).
Ramachandran teaches that said method provides resulting hydrogel microbeads/microparticles having an average (mean) maximum surface-to-surface dimension of less than 2 mm, e.g., ranging from 50 μm to 750 μm (Para. 0032 as applied to claims 9, 10, 19, 20).
Ramachandran does not specifically teach the use of methacrylated hyaluronic acid, and/or sodium hyaluronate (claims 1, 11), and also does not teach the use of such biological material as a steroid hormone, i.e., testosterone, estradiol and/or combinations thereof (claims 1, 11).
Ott teaches preparation of non-alginate hydrogel microparticles for encapsulating biologics (Abstract; Para. 0002), wherein said hydrogel microparticles are fabricated, e.g., by using methacrylated hyaluronic acid. e.g., crosslinked by UV exposure (Abstract; Para. 0004-0008, 0054-0056), and wherein said microparticles may include hormones (Claim 21; Para. 0065). Ott further teaches that said microparticles can also include polyethylene glycol, hyaluronan, fibrin, chitosan, collagen, fibronectin, laminin, and such media components as sodium (Para. 0004, 0059, 0065).
Grover teaches compositions and methods for sustained drug release from an injectable hydrogel (Title), wherein upon injection the drug, e.g., hormone/testosterone, is encapsulated within the hydrogel (Para. 0038), and wherein said hydrogels may be used to deliver small molecules such as steroids, e.g., to be used for testosterone replacement therapy (Para. 0015).
It would have been obvious to one of ordinary skill in the before the effective filing date of the claimed invention to use/try methacrylated hyaluronic acid as taught by Ott preparing hydrogel microparticles comprising a biological agent as taught by Ramachandran. One would do so with expectation of beneficial results, because Ott teaches that said microparticles can be used for providing controlled/sustained release of biological agents, e.g., hormones, incorporated therein. It also would be obvious to use/try such active agent as steroid hormones, e.g., testosterone, as taught by Grover to be included into hydrogel microparticles as taught by Ramachandran and Ott. One would do so with expectation of beneficial results, because the cited prior art teaches that said approach will provide hydrogel microparticles without alginate and providing controlled/sustained release of incorporated biological agents.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Salamone et al., US 20160303281A1 (cited in IDS) - teaches crosslinked microgel particles (e.g., spheres, ellipses, etc.) that can be coated, injected, sprayed, or implanted in tissues, organs, and may include such hormones as estradiol, testosterone and combinations thereof (Claim 14; Para. 0043, 0062, 0097)
US 2022/0143270 A1 – teaches core/shell microparticles (e.g., spheres, ellipses, etc.) that may include such active agent as androgen/testosterone, estrogen, etc. (Para. 0121-0122, 0155-0157)
Response to Arguments
Applicant's arguments, filed 03/31/2026, have been fully considered, but they were not found to be persuasive for the reasons set forth above. New objections, rejections and reference(s) have been added to the record to clarify the position of the examiner and/or to address newly introduced amendments.
In response to the applicant’s arguments regarding the reference by Ho, it is noted that said reference has not been used previously in the rejection. Therefore, the applicant’s statement is unclear and needs to be clarified. Applicant is advised to clarify the claim language, the structure of compounds to be used in the claimed method and clearly point out the patentable novelty, which the applicant thinks the claims present in view of the state of the art disclosed by the references cited, to place the application in condition for allowance.
Conclusion
No claim is allowed at this time.
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 OLGA V. TCHERKASSKAYA whose telephone number is (571)270-3672. The examiner can normally be reached 9 am - 6 pm, Monday - Friday.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert A. Wax can be reached at (571) 272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/OLGA V. TCHERKASSKAYA/
Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
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