DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after 16 March 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Election/Restriction
Applicant’s election without traverse of Group II, claims 15-20 and 25, and the species perfluorohexane (C6F14), bFGF (interpreted as an abbreviation for basic fibroblast growth factor), mesenchymal stem cells (MSCs), a hydrogel containing alginate, a composition comprising fibrin, alginate, and hyaluronic acid, 2.5 MHz, and >4 MPa in the reply filed on 1 July 2026, is acknowledged.
Status of Claims
Claims 1-2, 4, 6-7, 9, 13, 15-20, 25, 27-28, 31, 36, 39, and 42 are pending in the instant Office Action.
Claims 1-2, 4, 6-7, 9, 13, 27-28, 31, 36, 39, and 42 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 1 July 2026.
Claims 15-20 and 25 are under consideration in the instant Office Action, to the extent of the following elected species:
the specific perfluorocarbon perfluorohexane (C6F14);
the specific one or more active agents bFGF;
the specific plurality of cells mesenchymal stem cells (MSCs); and
the specific additional hydrogel layer of claim 17 a hydrogel containing alginate.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 23 May 2025, and 26 February 2026, were filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDSs are being considered by the examiner.
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 19-20 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 19 and 20 recite “the perfluorocarbon-containing emulsion” in lines 1-2 of each claim. This limitation lacks antecedent basis because neither claims 19-20 nor claim 15, from which claims 19-20 depend, recite “a perfluorocarbon-containing emulsion”. Claim 15 recites “at least one spatially-patterned perfluorocarbon-containing emulsion” and it is unclear if the limitations in claims 19-20 are limiting one perfluorocarbon-containing emulsion, more than one perfluorocarbon-containing emulsion, or all perfluorocarbon-containing emulsions. Applicant may overcome this rejection by amending claims 19-20 to recite “the at least one perfluorocarbon-containing emulsion”.
Claim 20 also recites “the droplet surface” and “the droplet” in lines 2-3. These limitations lack antecedent basis because neither claim 20 nor claim 15, from which claim 20 depends, recite a droplet. Applicant may overcome this rejection by amending claim 20 to depend from claim 19 or by amending claim 20 to recite the at least one perfluorocarbon-containing emulsion to comprise perfluorocarbon droplets.
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 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 15, 19-20, and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Fabilli et al. (U.S. Patent No. 10,709,812 B2, priority to 23 September 2016, cited by Applicant in the IDS filed on 26 February 2026, hereafter referred to as Fabilli) as evidenced by Litvinov et al. (Fibrinogen and Fibrin. In: Harris, J.R., Marles-Wright, J. (eds) Macromolecular Protein Complexes III: Structure and Function. 2021. Subcellular Biochemistry, vol 96. Springer, Cham., hereafter referred to as Litvinov).
Fabilli teaches a biodegradable hydrogel in the form of a tissue scaffold comprising a perfluorocarbon emulsion (Title and Abstract). The tissue scaffold is taught to comprise a hydrogel scaffold that is biodegradable and contains a perfluorocarbon (PFC) emulsion that vaporizes from liquid droplets into gas bubbles (col. 7, line 65 - col. 8, line 5). Scaffolds made from fibrin-based hydrogels which comprise “sonosensitive PFC emulsions” are termed “acoustically responsive scaffolds (ARSs)” (col. 7, lines 8-11), therefore the tissue scaffold comprising a hydrogel and a PFC emulsion that vaporizes from liquid droplets into gas bubbles is considered equivalent to the acoustically-responsive scaffold recited in instant claim 15.
Fabilli teaches the hydrogel of their invention to comprise alginate, hyaluronic acid, and/or a mixture of fibrinogen and thrombin which produces fibrin as evidenced by Litvinov pg. 475 (col. 9, lines 21-38), and the PFC emulsion is taught to comprise perfluorohexane and/or perfluorooctane (col. 13, lines 22-26). The liquid droplets are taught to vaporize in response to ultrasound stimulation or increased temperature (col. 8, lines 5-8, col. 13, lines 56-58, and claim 1). The emulsion may be a single or double emulsion (col. 13, lines 12-22) and comprises droplets which may carry a hydrophilic therapeutic agent, lipophilic therapeutic agent, or both (col. 13, lines 41-52). In Example 1, Fabilli teaches that expansion of their scaffold may be controlled by “spatially patterning bubble formation”, which is considered equivalent to the “spatially-patterned perfluorocarbon-containing emulsion” recited in instant claim 15. In one embodiment, the therapeutic agent is the protein fibroblast growth factor basic, which is considered to be equivalent to the elected bFGF (col. 20, line 10). Finally, Fabilli teaches that their scaffold may comprise a progenitor cell, which is equivalent to a stem cell as evidenced by para. [0083] of the instant spec., and in one embodiment the progenitor cell is a mesenchymal progenitor cell (col. 3, lines 29-35, col. 9, lines 39-43, and col. 12, line 62 - col. 13, line 8).
Although “picking, choosing, and combining various disclosures not directly related to each other by the teachings of the cited reference...has no place in...a 102, anticipation rejection,” picking and choosing may be entirely proper in an obviousness rejection. In re Arkley, 455 F.2d 586, 587 (CCPA 1972). Addressing the issue of obviousness, the Supreme Court noted that analysis under 35 U.S.C. 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ” (KSR v. Teleflex, 127 S.Ct. 1727, 1741 (2007)). The Court further emphasized that “[a] person of ordinary skill is…a person of ordinary creativity, not an automaton” (Id. at 1742).
The only difference between Fabilli and instant claims 15, 19-20, and 25 is that Fabilli does not teach the specific combination of components as claimed in a single embodiment (e.g., an ARS comprising a hydrogel comprising fibrin, alginate, and/or hyaluronic acid, at least one spatially-patterned PFC-containing emulsion, bFGF, and MSCs), or with sufficient specificity to be anticipatory. The specific combination of features claimed is disclosed within the teaching of Fabilli, but such “picking and choosing” within several variables does not necessarily give rise to anticipation. Where, as here, the reference does not provide any explicit motivation to select this specific combination of variables, anticipation cannot be found. However, it must be remembered that “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious.” See MPEP § 2141.I. Consistent with this reasoning, it would have been prima facie obvious to a person having ordinary skill in the art, prior to the effective filing date of the instant application, to have selected various combinations of the various disclosed ingredients from within the teachings of Fabilli, to arrive at an invention such as the one being sought in instant claims 15, 19-20, and 25.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Fabilli (U.S. Patent No. 10,709,812 B2, priority to 23 September 2016, cited by Applicant in the IDS filed on 26 February 2026) as evidenced by Litvinov (Fibrinogen and Fibrin. In: Harris, J.R., Marles-Wright, J. (eds) Macromolecular Protein Complexes III: Structure and Function. 2021. Subcellular Biochemistry, vol 96. Springer, Cham.) as applied to claims 15, 19-20, and 25 above, and further in view of Yao et al. (Nanoscale 2016, 8 (19), 10252., hereafter referred to as Yao).
Fabilli has been described above.
Fabilli does not teach the hydrogel to comprise aligned fibrin fibers. This deficiency is offset by the teachings of Yao.
Yao teaches the effect of fibrin fiber alignment in hydrogels on stem cell differentiation (Title and Abstract). The biophysical properties of biomaterials such as hydrogels are taught to be important due to their effect on the growth, differentiation, and eventual fate of implanted cells (pg. 10252, Introduction, para. 2). Yao designed an aligned fibrillar fibrin hydrogel (AFG) and assessed its biophysical properties and impact on mesenchymal stem cells (pg. 10253, right col., para. 2). Yao concluded that the aligned fibrin hydrogels were superior to randomly aligned fibrin hydrogel (RFG) and tissue culture plates in promoting differentiation of the mesenchymal stem cells and neurite outgrowth (Abstract and pg. 10263, Conclusion).
It would have been prima facie obvious to a person of ordinary skill in the art, prior to the filing of the instant application, to modify the invention of Fabilli with the teachings of Yao to use aligned fibrin fibers because the use of a known technique in similar devices to impart a known benefit yields predictable results. Fabilli rendered obvious an ARS comprising a hydrogel comprising fibrin, alginate, and/or hyaluronic acid, a spatially-patterned perfluorohexane-containing emulsion, bFGF encapsulated in the emulsion that releases upon ultrasound stimulation, and mesenchymal progenitor cells. In view of the teachings of Yao, an ordinary artisan would be motivated to use aligned fibrin fibers in the hydrogel of Fabilli because Yao teaches aligned fibrin to be superior to randomly align fibrin in promoting MSC differentiation and eventual neurite outgrowth. One of ordinary skill would find this property desirable in a device that comprises MSCs and would therefore desire its inclusion in their invention. As a result, there is a reasonable expectation of success in arriving at the invention of instant claim 16 in view of the teachings of Fabilli and further in view of the teachings of Yao.
Claims 17-18 are rejected under 35 U.S.C. 103 as being unpatentable over Fabilli (U.S. Patent No. 10,709,812 B2, priority to 23 September 2016, cited by Applicant in the IDS filed on 26 February 2026) as evidenced by Litvinov (Fibrinogen and Fibrin. In: Harris, J.R., Marles-Wright, J. (eds) Macromolecular Protein Complexes III: Structure and Function. 2021. Subcellular Biochemistry, vol 96. Springer, Cham.) as applied to claims 15, 19-20, and 25 above, and further in view of Tao et al. (ACS Appl. Mater. Interfaces 2019, 11 (40), 37139., hereafter referred to as Tao).
Fabilli has been described above.
Fabilli does not teach the hydrogel to comprise aligned fibrin fibers nor to comprise an additional hydrogel layer that is rigid and comprises alginate. These deficiencies are offset by the teachings of Tao.
Tao teaches hydrogel composites with a sandwich structure in which two rigid outer layers are on either side of a soft inner layer and impart high strength and toughness (Abstract). Double-network (DN) gels are taught to have imparted high strength and toughness to hydrogels and inspired others to form “tough composites from two mechanically different components” (pg. 37139, Introduction, para. 1). Tao further advanced this idea to forming hydrogel composites with an internal “soft matrix” and “rigid skeleton” outer layers (pg. 37140, left col., para. 2 and Scheme 1). Following characterization of the mechanical properties of the composite hydrogels, Tao concluded that rigid outer layers of the hydrogel provided mechanical toughness, “imparting high modulus and rupturing to dissipate energy” under stress (pg. 37141, right col., para. 1 and pg. 37145, Conclusions).
It would have been prima facie obvious to a person of ordinary skill in the art, prior to the filing of the instant application, to modify the invention rendered obvious by the teachings of Fabilli to have an additional, rigid layer comprising alginate in view of the teachings of Tao because combining prior art elements in similar inventions to impart a known benefit yields predictable results. The teachings of Fabilli rendered obvious an ARS comprising a hydrogel comprising fibrin, alginate, and/or hyaluronic acid, a spatially-patterned perfluorohexane-containing emulsion, bFGF encapsulated in the emulsion that releases upon ultrasound stimulation, and mesenchymal progenitor cells. In view of the teachings of Tao, an ordinary artisan would be motivated to add an additional rigid hydrogel layer possessing different mechanical properties to their scaffold to impart higher strength and toughness, which are properties that a person of ordinary skill would recognize as desirable. The ordinary artisan would find it obvious to formulate the additional layer as comprising alginate because the other layer of the hydrogel was taught by Fabilli to comprise fibrin, alginate, and/or hyaluronic acid and one of ordinary skill would maintain consistency of the composition throughout the layers of the scaffold. As a result, there is a reasonable expectation of success in arriving at the invention of claims 17-18 in view of the teachings of Fabilli and further in view of the teachings of Tao.
Claims 15, 19-20, and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Fabilli et al. (U.S. Patent No. 10,335,368 B2, priority to 26 February 2016, cited by Applicant in the IDS filed on 23 May 2025, hereafter referred to as Fabilli 2) as evidenced by Litvinov (Fibrinogen and Fibrin. In: Harris, J.R., Marles-Wright, J. (eds) Macromolecular Protein Complexes III: Structure and Function. 2021. Subcellular Biochemistry, vol 96. Springer, Cham.).
Fabilli 2 teaches a device comprising a tissue scaffold and an emulsion comprising PFC droplets which encapsulate a therapeutic agent (col. 3, lines 59-63). The PFC droplets are taught to vaporize in response to ultrasound and/or acoustic pressure (col. 3, lines 62-64), which is considered equivalent to the acoustically-responsive scaffold recited in instant claim 15, and the tissue scaffold is taught to be made from hydrogels which may be made from alginate, hyaluronic acid, and/or a mixture of fibrinogen and thrombin which produces fibrin as evidenced by Litvinov pg. 475 (col. 8, lines 26-44). One specific PFC taught by Fabilli 2 is perfluorohexane (Example 4 and col. 43, lines 1-2). Fabilli 2 notes that “tissue scaffold”, “scaffold”, and “hydrogel scaffold” are interchangeable (col. 8, lines 16-17). The scaffolds are further taught to comprise a progenitor cell, which is equivalent to a stem cell as evidenced by para. [0083] of the instant spec., and in one embodiment the progenitor cell is a mesenchymal progenitor cell (col. 4, lines 19-25). The therapeutic agent is taught in one embodiment to be the polypeptide bFGF and its release is taught to be controlled spatially (col. 3, lines 58-65 and col. 18, line 50). Finally, Fabilli 2 teaches spatial patterning of bubbles and acoustic droplet vaporization via ultrasound stimulus, which is considered equivalent to the “spatially-patterned perfluorocarbon-containing emulsion” recited in instant claim 15 (col. 27, lines 53-58, col. 33, lines 42-45, col. 34, lines 2-5, and col. 36, lines 46-50).
Although “picking, choosing, and combining various disclosures not directly related to each other by the teachings of the cited reference...has no place in...a 102, anticipation rejection,” picking and choosing may be entirely proper in an obviousness rejection. In re Arkley, 455 F.2d 586, 587 (CCPA 1972). Addressing the issue of obviousness, the Supreme Court noted that analysis under 35 U.S.C. 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ” (KSR v. Teleflex, 127 S.Ct. 1727, 1741 (2007)). The Court further emphasized that “[a] person of ordinary skill is…a person of ordinary creativity, not an automaton” (Id. at 1742).
The only difference between Fabilli 2 and instant claims 15, 19-20, and 25 is that Fabilli 2 does not teach the specific combination of components as claimed in a single embodiment (e.g., an ARS comprising a hydrogel comprising fibrin, alginate, and/or hyaluronic acid, at least one spatially-patterned PFC-containing emulsion, bFGF, and MSCs), or with sufficient specificity to be anticipatory. The specific combination of features claimed is disclosed within the teaching of Fabilli 2, but such “picking and choosing” within several variables does not necessarily give rise to anticipation. Where, as here, the reference does not provide any explicit motivation to select this specific combination of variables, anticipation cannot be found. However, it must be remembered that “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious.” See MPEP § 2141.I. Consistent with this reasoning, it would have been prima facie obvious to a person having ordinary skill in the art, prior to the effective filing date of the instant application, to have selected various combinations of the various disclosed ingredients from within the teachings of Fabilli 2, to arrive at an invention such as the one being sought in instant claims 15, 19-20, and 25.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Fabilli 2 (U.S. Patent No. 10,335,368 B2, priority to 26 February 2016, cited by Applicant in the IDS filed on 23 May 2025) as evidenced by Litvinov (Fibrinogen and Fibrin. In: Harris, J.R., Marles-Wright, J. (eds) Macromolecular Protein Complexes III: Structure and Function. 2021. Subcellular Biochemistry, vol 96. Springer, Cham.) as applied to claims 15, 19-20, and 25 above, and further in view of Yao (Nanoscale 2016 8 (19), 10252.).
Fabilli 2 has been described above.
Fabilli 2 does not teach the hydrogel to comprise aligned fibrin fibers. This deficiency is offset by the teachings of Yao.
Yao has been described above
It would have been prima facie obvious to a person of ordinary skill in the art, prior to the filing of the instant application, to modify the invention of Fabilli 2 with the teachings of Yao to use aligned fibrin fibers because the use of a known technique in similar devices to impart a known benefit yields predictable results. Fabilli 2 rendered obvious an ARS comprising a hydrogel comprising fibrin, alginate, and/or hyaluronic acid, a spatially-patterned perfluorohexane-containing emulsion, bFGF encapsulated in the emulsion that releases upon ultrasound stimulation, and mesenchymal progenitor cells. In view of the teachings of Yao, an ordinary artisan would be motivated to use aligned fibrin fibers in the hydrogel of Fabilli 2 because Yao teaches aligned fibrin to be superior to randomly align fibrin in promoting MSC differentiation and eventual neurite outgrowth. One of ordinary skill would find this property desirable in a device that comprises MSCs and would therefore desire its inclusion in their invention. As a result, there is a reasonable expectation of success in arriving at the invention of instant claim 16 in view of the teachings of Fabilli 2 and further in view of the teachings of Yao.
Claims 17-18 are rejected under 35 U.S.C. 103 as being unpatentable over Fabilli 2 (U.S. Patent No. 10,335,368 B2, priority to 26 February 2016, cited by Applicant in the IDS filed on 23 May 2025) as evidenced by Litvinov (Fibrinogen and Fibrin. In: Harris, J.R., Marles-Wright, J. (eds) Macromolecular Protein Complexes III: Structure and Function. 2021. Subcellular Biochemistry, vol 96. Springer, Cham.) as applied to claims 15, 19-20, and 25 above, and further in view of Tao (ACS Appl. Mater. Interfaces 2019, 11 (40), 37139.).
Fabilli 2 has been described above.
Fabilli 2 does not teach the hydrogel to comprise aligned fibrin fibers nor to comprise an additional hydrogel layer that is rigid and comprises alginate. These deficiencies are offset by the teachings of Tao.
Tao has been described above.
It would have been prima facie obvious to a person of ordinary skill in the art, prior to the filing of the instant application, to modify the invention rendered obvious by the teachings of Fabilli 2 to have an additional, rigid layer comprising alginate in view of the teachings of Tao because combining prior art elements in similar inventions to impart a known benefit yields predictable results. The teachings of Fabilli 2 rendered obvious an ARS comprising a hydrogel comprising fibrin, alginate, and/or hyaluronic acid, a spatially-patterned perfluorohexane-containing emulsion, bFGF encapsulated in the emulsion that releases upon ultrasound stimulation, and mesenchymal progenitor cells. In view of the teachings of Tao, an ordinary artisan would be motivated to add an additional rigid hydrogel layer possessing different mechanical properties to their scaffold to impart higher strength and toughness, which are properties that a person of ordinary skill would recognize as desirable. The ordinary artisan would find it obvious to formulate the additional layer as comprising alginate because the other layer of the hydrogel was taught by Fabilli 2 to comprise fibrin, alginate, and/or hyaluronic acid and one of ordinary skill would maintain consistency of the composition throughout the layers of the scaffold. As a result, there is a reasonable expectation of success in arriving at the invention of claims 17-18 in view of the teachings of Fabilli 2 and further in view of the teachings of Tao.
Claims 15, 19-20, and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Fabilli et al. (Acta Biomaterialia 2013, 9, 7399., cited by Applicant in the IDS filed on 23 May 2025, hereafter referred to as Fabilli 3) in view of Aliabouzar et al. (Ultrason. Sonochem. 2020, 66, 105109., provided by Applicant in the IDS filed on 23 May 2025, hereafter referred to as Aliabouzar).
Fabilli 3 teaches a delivery system comprising fibrin hydrogels “doped with growth factor-loaded double emulsion”, specifically bFGF, and is released via acoustic droplet vaporization (ADV) via ultrasound exposure (Abstract). ADV is taught to be achieved via an emulsion that comprises PFCs, in one embodiment perfluoropentane (PFP), which is taught to act as a diffusion barrier for the hydrophilic growth factor in the emulsion in addition to facilitating release of the bFGF following vaporization (pg. 7400, left col., para. 2). The droplet-hydrogel composites were further taught to comprise cells, which in one embodiment are mesenchymal progenitor cells, which are equivalent to mesenchymal stem cells as evidenced by para. [0083] of the instant spec. (pg. 7403, 3.5 Responses of cells to droplet-hydrogel composites).
Fabilli 3 does not teach the specific PFC perfluorohexane. This deficiency is offset by the teachings of Aliabouzar.
Aliabouzar teaches the use of an ultrasound standing wave field (SWF) in ARSs to release two different biologically active “payloads” with spatiotemporal control (Abstract). In tissue regeneration applications, Aliabouzar teaches that multiple growth factors are a necessity, which subsequently necessitates a delivery system that can deliver two “surrogate payloads…in separate emulsions, each having a unique ADV threshold” (pg. 1-2, Introduction, para. 2). To meet this goal, Aliabouzar teaches an ARS comprising two layers with two different PFC and payload-containing emulsions that utilize the elevated amplitudes afforded by SWF to sequentially release the payloads (pg. 2, left col., para. 2-3). The PFC and payload-containing emulsions sequentially released in the bi-layer ARS each comprised perfluorohexane (described as “C6”) as the PFC that enabled ADV (Table 1 and pg. 8-10, Dual payload release).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the filing of the instant application, to use perfluorohexane in the invention taught by Fabilli 3 in view of the teachings of Aliabouzar because simple substitution of one element for another to enable enhanced functionality taught in a similar product yields predictable results. Fabilli 3 teaches an ARS comprising a hydrogel comprising fibrin, a spatially-patterned perfluoropentane-containing emulsion, bFGF encapsulated in the emulsion that releases upon ultrasound stimulation, and mesenchymal progenitor cells. In view of the teachings of Aliabouzar, a person of ordinary skill would be motivated to substitute perfluorohexane for perfluoropentane in the PFC-emulsion of the invention taught by Fabilli 3 because Aliabouzar teaches the PFC to be useful in an ARS that possess dual functionality in delivering multiple “payloads” with different ultrasound frequencies and with spatiotemporal control. The ordinary artisan would desire enhanced functionality in their invention and would therefore be motivated to substitute the PFCs. As a result, there is a reasonable expectation of success in arriving at the invention of claims 15, 19-20, and 25 in view of the teachings of Fabilli 3 and Aliabouzar.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Fabilli 3 (Acta Biomaterialia 2013, 9, 7399., cited by Applicant in the IDS filed on 23 May 2025) in view of Aliabouzar (Ultrason. Sonochem. 2020, 66, 105109., provided by Applicant in the IDS filed on 23 May 2025) as applied to claims 15, 19-20, and 25 above, and further in view of Yao (Nanoscale 2016 8 (19), 10252.).
Fabilli 3 and Aliabouzar have been described above.
Fabilli 3 and Aliabouzar do not teach the fibrin fibers comprising the hydrogel to be aligned. This deficiency is offset by the teachings of Yao.
Yao has been described above
It would have been prima facie obvious to a person of ordinary skill in the art, prior to the filing of the instant application, to modify the invention rendered obvious by the teachings of Fabilli 3 and Aliabouzar with the teachings of Yao to use aligned fibrin fibers because the use of a known technique in similar devices to impart a known benefit yields predictable results. Fabilli 3 and Aliabouzar rendered obvious an ARS comprising a hydrogel comprising fibrin, a spatially-patterned perfluorohexane-containing emulsion, bFGF encapsulated in the emulsion that releases upon ultrasound stimulation, and mesenchymal progenitor cells. In view of the teachings of Yao, an ordinary artisan would be motivated to use aligned fibrin fibers in the hydrogel of Fabilli 3 because Yao teaches aligned fibrin to be superior to randomly align fibrin in promoting MSC differentiation and eventual neurite outgrowth. One of ordinary skill would find this property desirable in a device that comprises MSCs and would therefore desire its inclusion in their invention. As a result, there is a reasonable expectation of success in arriving at the invention of instant claim 16 in view of the teachings of Fabilli 3 and Aliabouzar and further in view of the teachings of Yao.
Claims 17-18 are rejected under 35 U.S.C. 103 as being unpatentable over Fabilli 3 (Acta Biomaterialia 2013, 9, 7399., cited by Applicant in the IDS filed on 23 May 2025) in view of Aliabouzar (Ultrason. Sonochem. 2020, 66, 105109., provided by Applicant in the IDS filed on 23 May 2025) as applied to claims 15, 19-20, and 25 above, and further in view of Tao (ACS Appl. Mater. Interfaces 2019, 11 (40), 37139.) and Lee et al. (Prog. Polym. Sci. 2012, 37 (1), 106., hereafter referred to as Lee).
Fabilli 3 and Aliabouzar have been described above, and particularly relevant to claims 17-18 Aliabouzar teaches a two layered hydrogel with different payloads to be delivered following ultrasound stimulation (vide supra).
Fabilli 3 and Aliabouzar do not teach do not teach the delivery system to comprise an additional hydrogel layer that is rigid and comprises alginate. These deficiencies are offset by the teachings of Tao and Lee.
Tao has been described above.
Lee teaches a review of the properties of alginate and its hydrogels, biomedical applications of alginate hydrogels, and future applications (Abstract). Alginate is taught to be a naturally occurring polymer that is biocompatible, has low toxicity, has a relatively low cost to produce, and has structure similarity to living tissue (pg. 107, Introduction, para. 2). Alginate hydrogels are further taught to be useful for delivering low molecular weight drugs and proteins and facilitating tissue regeneration, utilizing diffusion or controlled degradation to selectively deliver therapeutic agents (pg. 113-118, 4. Biomedical applications). Lee concludes that alginate and its hydrogels have “great utility and potential as a biomaterial for many biomedical applications” and that its most attractive features include “biocompatibility, mild gelation conditions, and simple modifications to prepare alginate derivatives with new properties”, in addition to having a history of successful clinical applications (pg. 122, 5. Conclusions and future perspectives).
It would have been prima facie obvious to a person of ordinary skill in the art, prior to the filing of the instant application, to modify the invention rendered obvious by the teachings of Fabilli 3 and Aliabouzar to have an additional, rigid layer comprising alginate in view of the teachings of Tao and Lee because combining prior art elements in similar inventions to impart a known benefit yields predictable results. The teachings of Fabilli 3 and Aliabouzar rendered obvious an ARS comprising a hydrogel comprising fibrin, a spatially-patterned perfluorohexane-containing emulsion, bFGF encapsulated in the emulsion that releases upon ultrasound stimulation, and mesenchymal progenitor cells. In view of the teachings of Tao, an ordinary artisan would be motivated to add an additional rigid hydrogel layer possessing different mechanical properties to their scaffold to impart higher strength and toughness, which are properties that a person of ordinary skill would recognize as desirable. The ordinary artisan would find it obvious to formulate the additional layer as comprising alginate because Lee teaches the material to be biocompatible, nontoxic, modifiable, and useful for delivering drugs and/or proteins, which are properties the ordinary artisan would find desirable in their ARS and would be motivated to include. As a result, there is a reasonable expectation of success in arriving at the invention of claims 17-18 in view of the teachings of Fabilli 3 and Aliabouzar and further in view of the teachings of Tao and Lee.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
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Claims 15-20 and 25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 and 15-16 of U.S. Patent No. 10,335,368 B2 (priority to 26 February 2026, cited by Applicant in the IDS filed on 23 May 2025, referred to as Fabilli 2) in view of Fabilli (U.S. Patent No. 10,709,812 B2, priority to 23 September 2016, cited by Applicant in the IDS filed on 26 February 2026) as evidenced by Litvinov et al. (Fibrinogen and Fibrin. In: Harris, J.R., Marles-Wright, J. (eds) Macromolecular Protein Complexes III: Structure and Function. 2021. Subcellular Biochemistry, vol 96. Springer, Cham., hereafter referred to as Litvinov), Yao (Nanoscale 2016, 8 (19), 10252.), Tao (ACS Appl. Mater. Interfaces 2019, 11 (40), 37139.), and Lee (Prog. Polym. Sci. 2012, 37 (1), 106.).
Fabilli 2 recites a method of delivering a therapeutic agent utilizing an ARS comprising a hydrogel and two emulsions each comprising a PFC and a therapeutic agent and exposing the scaffold to ultrasound stimulus to deliver the therapeutic agent(s) (claim 1). The device is further recited as comprising a progenitor cell, in once embodiment a mesenchymal progenitor cell, which is equivalent to a stem cell as evidenced by para. [0083] of the instant spec. (claims 2-3). Fabilli 2 additionally recites that the therapeutic agents may be a polypeptide and that their delivery is controlled spatially, which is interpreted as being equivalent toa spatially-patterned emulsion as recited in instant claim 15 (claims 15-16).
Fabilli 2 does not recite the materials comprising the hydrogel of their invention, a specific PFC, the polypeptide to be bFGF, nor the hydrogel to comprise an additional layer that is rigid and comprising alginate. These deficiencies are offset by the teachings of Fabilli, Yao, Tao, and Lee.
Fabilli, Yao, Tao, and Lee have been described above.
Instant claims 15-20 and 25 are obvious variations of commonly assigned U.S. Patent No. 10,335,368 B2 (Fabilli 2) because it would have been prima facie obvious to a person of ordinary skill in the art at the time of filing to modify the hydrogel scaffold recited in the method of Fabilli 2 to comprise fibrin, alginate, and/or hyaluronic acid, to use aligned fibrin fibers, to comprise an additional rigid layer comprising alginate, to use perfluorohexane, and to use bFGF as the polypeptide therapeutic agent in view of the teachings of Fabilli, Yao, Tao, and Lee.
While the invention recited by Fabilli 2 is directed to a method, it would be obvious to a person of ordinary skill to modify the hydrogel scaffold recited by Fabilli 2 used in their method to deliver therapeutic agents in response to ultrasound stimulus. A person of ordinary skill in the art would be motivated to use fibrin, alginate, and/or hyaluronic acid to comprise the scaffold recited by Fabilli 2 in view of the teachings of Fabilli because Fabilli 2 does not recite a material comprising the scaffold of their invention and Fabilli teaches missing information an ordinary artisan would need to complete their invention. Similarly, Fabilli 2 does not teach a specific PFC and one of ordinary skill would be motivated to use perfluorohexane in view of the teachings of Fabilli because the reference teaches missing information and that perfluorohexane is appropriate to use in emulsions that deliver a therapeutic agent following ultrasound stimulus. Further, while Fabilli 2 recites a polypeptide to be a therapeutic agent in their hydrogel scaffold, they do not recite a specific species. In view of the teachings of Fabilli, it would have been obvious to use bFGF as the specific polypeptide because Fabilli teaches it to be a polypeptide that is suitable to be delivered via a hydrogel scaffold in response to ultrasound stimulus.
In view of the teachings of Yao, an ordinary artisan would be motivated to use aligned fibrin fibers in the hydrogel of Fabilli 2 because Yao teaches aligned fibrin to be superior to randomly align fibrin in promoting MSC differentiation and eventual neurite outgrowth. One of ordinary skill would find this property desirable in a device that comprises MSCs and would therefore desire its inclusion in their invention. In view of the teachings of Tao, an ordinary artisan would be motivated to add an additional rigid hydrogel layer possessing different mechanical properties to their scaffold to impart higher strength and toughness, which are properties that a person of ordinary skill would recognize as desirable. The ordinary artisan would find it obvious to formulate the additional layer as comprising alginate because Lee teaches the material to be biocompatible, nontoxic, modifiable, and useful for delivering drugs and/or proteins, which are properties the ordinary artisan would find desirable in their ARS and would be motivated to include in their invention.
Claims 15-20 and 25 are directed to an invention not patentably distinct from claims 1-3 and 15-16 of commonly assigned U.S. Patent No. 10,335,368 B2 in view of Fabilli as evidenced by Litvinov, Yao, Tao, and Lee. Specifically, see above.
The U.S. Patent and Trademark Office may not institute a derivation proceeding in the absence of a timely filed petition. The USPTO normally will not institute a derivation proceeding between applications or a patent and an application having common ownership (see 37 CFR 42.411). Commonly assigned U.S. Patent No. 10,335,368 B2, discussed above, may form the basis for a rejection of the noted claims under 35 U.S.C. 102 or 103 if the commonly assigned case qualifies as prior art under 35 U.S.C. 102(a)(2) and the patentably indistinct inventions were not commonly owned or deemed to be commonly owned not later than the effective filing date under 35 U.S.C. 100(i) of the claimed invention.
In order for the examiner to resolve this issue the applicant or patent owner can provide a statement under 35 U.S.C. 102(b)(2)(C) and 37 CFR 1.104(c)(4)(i) to the effect that the subject matter and the claimed invention, not later than the effective filing date of the claimed invention, were owned by the same person or subject to an obligation of assignment to the same person. Alternatively, the applicant or patent owner can provide a statement under 35 U.S.C. 102(c) and 37 CFR 1.104(c)(4)(ii) to the effect that the subject matter was developed and the claimed invention was made by or on behalf of one or more parties to a joint research agreement that was in effect on or before the effective filing date of the claimed invention, and the claimed invention was made as a result of activities undertaken within the scope of the joint research agreement; the application must also be amended to disclose the names of the parties to the joint research agreement.
A showing that the inventions were commonly owned or deemed to be commonly owned not later than the effective filing date under 35 U.S.C. 100(i) of the claimed invention will preclude a rejection under 35 U.S.C. 102 or 103 based upon the commonly assigned case. Alternatively, applicant may take action to amend or cancel claims such that the applications, or the patent and the application, no longer contain claims directed to patentably indistinct inventions.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure includes Liu et al. (Front. Chem. 2018, 6 (439), 1.) which teaches multi-layered hydrogels with various functions and/or properties in different layers, the benefits of 3D printing the hydrogels, and their applications in the biomedical field (Abstract).
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/S.J.S./
Examiner, Art Unit 1619
/TIGABU KASSA/Primary Examiner, Art Unit 1619
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