DETAILED ACTION
Status of the Application
Receipt is acknowledged of Applicants’ Amendments and Remarks, filed 5 May 2026, in the matter of Application N° 18/224,561. Said documents have been entered on the record. The Examiner further acknowledges the following:
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 2-4, 7, 11, 13, and 14 have been canceled. No claims have been added.
Claims 1 and 15 have been amended. Claim 15 is amended to depend from independent claim 12 in the wake of claim 13 being canceled.
Claim 1 has been significantly amended having added the limitations of canceled claims 2-4, 7, and 11 to the claim. Claim 1 has been additionally amended to newly recite that the core-shell structure is configured to control the release of the active ingredient and suppress an initial burst release of the active ingredient.
Thus, claims 1, 5-10, 12, and 15-17 now represent all claims currently under consideration.
Information Disclosure Statement
One new Information Disclosure Statement (IDS) filed 5 May 2026 is acknowledged and has been considered.
Withdrawn Rejections
Rejection under 35 USC 103
Applicants’ amendment to claim 1 adding the limitation of suppressing an initial burst release of the active ingredient is persuasive in overcoming the previously raised obviousness rejection. Of particular note is that the teachings of Jinzhong discloses core-shell nanofibers that exhibit burst release of the drug they carry. Additionally, on its own Jinzhong has been acknowledged as being deficient in its failure to disclose the amended polymer hyaluronic acid. The combination of amended limitations is thus considered persuasive in overcoming the previously raised rejection. Said rejection is withdrawn.
New Rejections
Applicants’ amendments have necessitated the following grounds of rejection:
Claim Rejections - 35 USC §112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1 and 5-10 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventors, at the time the application was filed, had possession of the claimed invention.
As amended, claim 1 now recites:
A nanofiber sheet for healing of a rotator cuff tear, the nanofiber sheet comprising:
a composition comprising teriparatide, isomers thereof, pharmaceutically acceptable salts thereof, hydrates thereof, or solvates thereof, as an active ingredient; and hyaluronic acid or salts thereof;
wherein nanofibers constituting the nanofiber sheet contain the composition therein [see original claims 2 and 3];
wherein the nanofibers have a core-shell structure in which a nanofiber shell surrounds a core comprising the composition [see e.g., original claim 4];
wherein the hyaluronic acid or salts thereof is a carrier for controlling release of the active ingredient [see original claim 11],
wherein the core-shell structure is configured to control release of the active ingredient and suppress an initial burst release of the active ingredient [new, unsupported limitation]; and
wherein the sheet is locally attached to the rotator cuff tear site [see original claim 7].
Having fully considered the originally-filed specification and claims, the Examiner notes that Applicants’ specification only appears to discuss the state-of-the-art with respect to formulations that provide initial burst release of an active (see pg. 14, lines 7-12 and pg. 23, lines 17-21). Both lines of alleged support cite journal publications that report on the studied formulations resulting in burst release with the former citation (Tissue Eng Part A; 2009) disclosing hyaluronic acid and nanofiber scaffolds as not having a significant effect on tendon to bone healing and the nanofiber scaffolds being known to provide burst release of the agent impregnated therein.
Additionally, there is no discussion provided within the originally-filed disclosure pertaining to any configuration of the core-shell nanofibers suppressing an initial burst of the active ingredient. The Examiner acknowledges that the structure is discussed, albeit no compositional limitations appear to be present defining the shell component. The Examiner also acknowledges that such a structure would present the skilled artisan with a reasonable expectation of establishing some measure of control of active release from the core within. However, suppression of an initial burst release is not a functional limitation that is further defined by any compositional or structural merits.
Thus, it is respectfully advanced that Applicants’ amendment to the applied composition constitutes new matter.
Consistent with MPEP §2163.06(I), the Examiner will still consider the subject matter of the amended claim in considering rejections based on the prior art since there exists the possibility that Applicants may potentially overcome the new matter rejection.
Claim Rejections - 35 USC §102
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 12 and 15-17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Han et al. (J. Shoulder Elbow Surg.; published only 22 March 2022).
The limitations of the instantly claimed method recite a method of manufacturing a nanofiber sheet comprising incorporating a composition comprising teriparatide, isomers thereof, pharmaceutically acceptable salts thereof, hydrates thereof, or solvates thereof, as an active ingredient; and hyaluronic acid or salts thereof in the formed sheet. Claim 16 recites that the method further forms nanofibers containing the composition therein by discharging the electrospinning solution from an external nozzle, and by discharging the composition containing teriparatide from an internal nozzle. Claim 17 recites limitations to the electrospinning solution in terms of the organic solvent used to form it.
Han expressly teaches the claimed method disclosing the use of a polycaprolactone (PCL) solution dissolved into a 75/25 mixture with dichloromethane and dimethylformamide for electrospinning that is processed to provide a microstructured framework that stabilizes the structure of the nanofiber sheet (see pg. 1629; right col.; Materials and methods). The reference also discloses production of nanofiber sheets composed of rhPTH-soaked nanofibers using hyaluronic acid as a carrier. The use of the HA is selected because it is a highly viscous polysaccharide that plays a crucial role in organizing the ECM in the human body, and because it is a known carrier for drugs, cells, and proteins. It is noted that the reference discloses that “the nanofiber scaffold has been reported to have shown a rapid burst release at an early stage after implantation” and that “HA played a highly important role as the rhPTH carrier herein to maintain the rhPTH concentration for a long period on the 3D-printed nanofiber sheet” (see paragraph bridging pp. 1629-1630). The reference additionally discloses that “[t]o avoid rapid burst release of the rhPTH from the sheet, we applied HA as a carrier to ensure sustained release” (see pg. 1637; left col., bottom).
The reference is thus considered to anticipate the instantly recited method claims.
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 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.
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. Applicants are 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, 5-10, 12, and 15-17 are rejected under 35 U.S.C. 103 as being unpatentable over Han et al. (J. Shoulder Elbow Surg.; published only 22 March 2022) in view of Xu et al. (CN 105536051 (A); machine translation provided and cited).
The limitations of amended claim 1 are discussed above. The limitations of claims 5, 6, and 8-10 are previously discussed. The limitations of claims 12 and 15-17 are discussed above.
Han discloses producing 3D-printed, electrospun, rhPTH-soaked and HA-soaked nanofiber sheets for the purpose of treating and promoting tendon-to-bone healing in humans and animals with rotator cuff tears (see e.g., Abstract; Materials and methods). Histological evaluation of the different formulation test groups revealed that group E (rhPTH-soaked and HA-soaked nanofiber sheets) showed denser collagen fibers and more mature tendon-to-bone junction than did the other groups, as well as a higher orientation of collagen fibers (see pg. 1634; right col.; Histologic evaluation; Table III).
According to Table II (pg. 1633), the Group E formulation also appears to provide the most increase to expression of COL1A1, COL3A1, BMP-2, SCX, SOX9, and ACAN.
The foregoing meets the limitations recited by instant claims 8 and 9.
The limitations of claims 5 and 6 remain directed to recitations of intended use, but are also expressly disclosed by Han.
The limitations of instant claim 10 are broadly and reasonably interpreted as being directed to product-by-process limitations. However, like claims 5 and 6, the limitations are expressly met by the disclosure of Han.
Lastly, each of the amended limitations of instant claim 1 are considered to be met by the teachings of Han with the exception of the core-shell structure of the nanofibers used to compose the nanofiber sheet.
What is understood by the teachings of Han is that the HA carrier that is used to produce the practiced nanofibers is one mechanism that is used to control the release of rhPTH from the fibers owing to the viscous nature of the polysaccharide. It does not disclose that the nanofibers possess a core-shell structure.
Xu is considered to remedy this deficiency disclosing the production of core-shell nanofibers by electrostatic spinning (see e.g., Abstract). The core-shell type nanofiber is taught as being used as a tissue engineering material, as having good biocompatibility and biodegradability, and as being used for loading and controllably releasing medicines therefrom (see e.g., Abstract). The claims of Xu disclose that the core-shell nanofiber scaffold is composed of a biocompatible material such as hyaluronic acid.
The sole deficiency of Xu is that the medicine carried by the core-shell nanofibers is not inclusive of teriparatide (i.e., rhPTH; recombinant human parathyroid hormone). What it does disclose though, is that the beneficial effects of the nanofibers include having a core-shell structure, where the core material is a cross-linked hydrogel and that by designing and customizing the cross-linking density of the hydrogel, the drug loading and its release rate can be effectively controlled.
Based on the combined teachings of the references, the Examiner submits that a person of ordinary skill in the art would have had a reasonable expectation of achieving controlled release of rhPTH from the nanofibers produced by Han by adding an outer shell layer to yield a core-shell nanofiber structure. Noting that Xu discloses each of the recited compositional, structural, and manufacturing limitations of the instantly claimed invention, with the exception of rhPTH, the Examiner submits that the skilled artisan would similarly reasonably expect in achieving the instant invention through the addition of rhPTH of Han to the nanofibers of Xu.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, and absent a clear showing of evidence to the contrary.
All claims have been rejected; no claims are allowed.
Conclusion
Applicants’ amendments 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 extension fee 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 Jeffrey T. Palenik whose telephone number is (571) 270-1966. The Examiner can normally be reached on 9:30 am - 7:00 pm; M-F (EST).
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Robert A. Wax can be reached on (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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/Jeffrey T. Palenik/
Primary Examiner, Art Unit 1615
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