DETAILED ACTION
Status of the Application
Receipt is acknowledged of Applicants’ claimed invention, filed 8 July 2024, 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 .
No additions, amendments, or cancellations have been made to the originally-filed claims. No new matter has been added.
Thus, claims 1-17 represent all claims currently under consideration.
Information Disclosure Statement
Five Information Disclosure Statements (IDS) filed 20 July 2023, 14 February 2024, 21 May 2025, and 7 October 2025 are acknowledged and have been considered.
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 1-17 are rejected under 35 U.S.C. 103 as being unpatentable over Jinzhong et al. (CN 104841022A; IDS reference; machine translation attached and cited) in view of Oh et al. (KR 20200114633A; IDS reference; machine translation attached and cited) and Honda et al. (AJSM; 2017; IDS reference).
The instantly claimed invention is directed to a nanofiber sheet comprising a composition comprising teriparatide, isomers, pharmaceutically acceptable salts, hydrates, or solvates thereof, as an active ingredient. Claims 2 and 3 recite that the sheet is impregnated with the composition and that the nanofibers contain the composition, respectively. Claim 4 recites that the fibers have a core-shell structure. Claim 11 recites that the composition further comprises hyaluronic acid.
Jinzhong discloses a nanofiber membrane applied for the treatment of a rotator cuff injury to rapidly promote tendon regeneration (see e.g., Abstract; ¶[0008]; ¶[0010]; claim 2). The practiced nanofiber membranes are disclosed as being prepared via electrospinning whereby the fibers will possess a core-shell structure (see e.g., ¶[0072]; ¶[0077]; claim 1). Here, the reference discloses a core formed using PLGA and basic fibroblast growth factor (bFGF) as the active cytokine. Paragraph [0016] discloses that in addition to PLGA, the biodegradable polymer may be formed from PLA, PGA, and polycaprolactone.
Paragraph [0017], for instance discloses that the administered cytokine active is encapsulated within the fiber (see also claims 1-5).
Jinzhong is considered to be deficient with respect to two aspects of the instantly claimed composition; the reference does not disclose including either teriparatide or hyaluronic acid.
Oh is considered to remedy the former deficiency disclosing a composition that is administered via local, subcutaneous injection to a rotator cuff repair site (see e.g., Abstract; claims). The composition is disclosed as comprising as the active ingredient, teriparatide, isomers, pharmaceutically acceptable salts, hydrates, or solvates thereof (see e.g., claim 1). The reference discloses that the teriparatide composition exhibits a tendon-to-bone healing effect when administered to patients undergoing rotator cuff treatment, thus lowering the rate or re-rupture, thereby having an excellent effect of improving healing after rotator cuff suturing (see e.g., Abstract).
The latter deficiency is remedied by the article published by Honda which reports on a study undertaken to analyze the efficacy of hyaluronic acid to provide tendon-to-bone healing in rotator cuff repair (see e.g., Abstract). Hyaluronic acid is recognized as a high-molecular weight polysaccharide that is present in the extracellular matrix (ECM) of soft connective tissue and synovial fluid and that it exerts different physiological roles in different tissues (see pg. 3323, left col., second full paragraph). The reference continues stating that “[m]esenchymal stem cells (MSCs) are one of the factors associated with tendon-to-bone healing in rotator cuff tears, although their precise role has not been elucidated. Cytokines and growth factors produced by MSCs can prompt chondrogenic differentiation and matrix production. [Hyaluronic acid] HA enhanced the attachment, proliferation, and phenotype of chondrocytes and promoted the chondrogenesis of MSC, showing the advantage of HA on the potential for cell-scaffold interactions via cell surface receptors, which direct cell behaviours and assist in stem cell differentiation.” (see pg. 3323, left col., third full paragraph) These results prompted Honda et al. to examine HA’s ability to accelerate tendon-to-bone healing in rotator cuff tears by activating MSCs at the surgical site. The study concludes that hyaluronic acid (i.e., HA-activated MSCs) does accelerate tendon-to-bone healing in the rotator cuff repair model, enhances the biomechanical strength and increases the chondroid formation and tendon maturity at the tendon-bone interface.
Based on the foregoing teachings of the references, the Examiner respectfully advances that a person of ordinary skill in the art, would have been motivated to modify the teachings of Jinzhong to include both, teriparatide and hyaluronic acid in the practiced nanofiber membrane.
MPEP §2144.06(I) states that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.”
In the instant case, the Examiner has presented compositions within the prior art, each of which are directed to the improvement of healing tendon-to-bone healing following treatment repairing rotator cuffs. Jinzhong discloses the membrane formed using core-shell structured, nanofiber polymer filaments that contain cytokine actives. Though deficient with respect to the two remaining compounds teriparatide and hyaluronic acid, the Examiner has demonstrated that both compounds are clearly known and established within the art as effecting positive tendon-to-bone healing following treatment for rotator cuff injury.
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.
The limitations recited by claim 5 recite further define the rotator cuff tear. Claim 6 recites that healing the rotator cuff tear includes healing the tear at the suture site after repair. Claim 7 recites that the sheet of claim 1 is locally attached to the rotator cuff tear site.
The Examiner submits that each of these claims is read on by the foregoing disclosures, notably as none of them adds to the compositional limitations presented in claim 1. Stated another way, the limitations of claims 5-7 are considered to further limit the intended use of the composition at issue.
The limitations of claim 8 recite that the sheet of claim 1 enhances at least one property such as maturation of tendon-to-bone junctions. The claim is broadly and reasonably considered to recite the same composition limitations presented by instant claim 1 and is therefore read on by the teachings discussed above. Further, the Examiner submits that Honda’s disclosure reports that hyaluronic acid “enhance[es] biomechanical strength and increase[es] chondroid formation and tendon maturity at the tendon-bone interface” (see Abstract; Discussion, pg. 3329).
The limitations of claim 9 recite that the sheet of claim 1 increases the expression level of one or more genes, such as collagen types I and III, BMP-2, scleraxis, SRY-box 9, and aggrecan. As above, claim 9 is also broadly and reasonably considered to recite the same composition limitations presented by instant claim 1 and is therefore read on by the teachings discussed above. Jinzhong at ¶[0097], for instance, discloses that the practiced composition is useful in optimizing collagen distribution at tendon-bone junction healing sites. Figure 8 of Honda for instance, depicts that hyaluronic acid consistently and significantly increased mRNA expression levels of collagen type 2, SOX9 (SRY-box 9), and aggrecan (see pg. 3329).
The limitations of claim 12 are directed to a method of producing a nanofiber sheet comprising incorporating a composition comprising a teriparatide as an active ingredient, into the sheet. Claim 13 recites forming the nanofiber sheet by electrospinning an electrospinning solution and impregnating the sheet with a composition comprising teriparatide as an active ingredient. Claims 14 and 16 recite that the electrospinning solution is produced by adding one or more of the recited polymers to an organic solvent.
Claim 15 recites that the solution further comprises hyaluronic acid.
Claim 16 recites forming the nanofibers by discharging the electrospinning solution from an external nozzle and by discharging the electrospinning solution comprising the teriparatide from an internal nozzle.
The method for forming the nanofiber membrane is disclosed by Jinzhong. Therein, ¶[0019]-¶[0022] discloses a preferred method for forming the fibers wherein the active cytokine(s) and excipients are dissolved in buffer solution and the biodegradable polymers in an organic solution. The active solution is added to the organic solvent containing the polymer materials, sonicated, and then electrospun to form the nanofiber membrane.
Paragraph [0077], as discussed above, discloses the core-shell structure as instantly claimed, as well as the active (e.g., bFGF) cytokine polymer core-shell arrangement.
As with the claimed composition, the foregoing is considered to teach each of the instantly claimed limitations with the exception of the teriparatide and hyaluronic acid.
Also, as discussed above, the Examiner again advances that a person of ordinary skill in art in possession of the combined teachings of Jinzhong, Oh, and Honda, would have found motivation to modify the nanofiber-forming method of Jinzhong so that it would incorporate both teriparatide and hyaluronic acid as active ingredients. Motivation stems from the showing that all three active ingredients, in each of the references are known in the art to be used for lending improved effect and results for tendon-to-bone healing in patients recovering from rotator cuff repair and treatment. See MPEP §2144.06(I).
Thus, the Examiner submits that a person of ordinary skill in the art would have had a reasonable expectation of success in arriving at the instantly claimed method of manufacturing the claimed membrane. 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.
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