DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant's election without traverse of Group I, claims 1-10 in the reply filed on 21 January 2026 is acknowledged. Claims 11-14 have been withdrawn. Claims 1-10 are currently pending and under examination.
This Application is a national phase application under 35 U.S.C. §371 of International Application No. PCT/PL2022/500004, filed 3 February 2022, which claims priority to Polish patent document No. PL437078, filed 22 February 2021.
Claim Objections
Claims 6 and 9 are objected to because of the following informalities: these claims include abbreviations without first reciting the full term. The full term should first be set forth in a claim followed by the abbreviation. Appropriate correction is required.
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 1-10 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.
Claim 1 recites the limitations "the form of microscaffolds" in line 2-3, and “the nonwoven fabric layer” in c) line 1. There is insufficient antecedent basis for these limitations in the claim. No form of microscaffolds and no nonwoven fabric layer is previously recited in the claim.
Further regarding claim 1, step c) recites:
c) laser cutting of the nonwoven fabric layer formed on the collector into individual detachable microscaffolds with a thickness between 0.01 and 0.2 mm and a cylindrical shape with a base diameter between 0.1 and 0.4 mm or a prism with a base edge length between 0.04 and 0.4 mm (emphasis added).
This claim is indefinite, because it is unclear if the individual detachable microscaffolds are intended to have:
a thickness between 0.01 and 0.2 mm and a cylindrical shape with a base diameter between 0.1 and 0.4 mm; OR only a prism with a base edge length between 0.04 and 0.4 mm (i.e. no thickness requirement if the shape is a prism); or
a thickness between 0.01 and 0.2 mm, and a shape, the shape being EITHER a cylindrical shape with a base diameter between 0.1 and 0.4 mm, or only a prism with a base edge length between 0.04 and 0.4 mm (i.e. a thickness requirement, and also a shape requirement).
Claim 4 recites that the collector is “selected from a group consisting of: a collector comprised of”; this limitation is indefinite, because it is unclear if “a group” is intended to refer to the group that follows this recitation, or instead, if “a group,” refers to any group. It is suggested that “a group” instead read “the group.”
Additionally regarding the noted limitation in claim 4, the phrase “a collector comprised of” is indefinite, because it is unclear how the collector is “comprised of” the cited material. It appears that this should instead read that the collector comprises the noted materials.
Claim 5 recites the limitation "the polymer solution" in line 3. There is insufficient antecedent basis for this limitation in the claim. No polymer solution is previously recited in the claims.
Further, the term “active substance” in claim 5 is a relative term which renders the claim indefinite. The term “active substance” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The metes and bounds of this term are indefinite, as it is unclear what substances are intended to be included in, or excluded from, this term. It is noted that the only “active substances” recited by applicant in the disclosure are growth factors.
Claim 6 recites that the active substance “is comprised of a growth factor”; this limitation is indefinite, because it is unclear how the active substance is “comprised of” a growth factor. It appears that this should instead read “the active substance comprises” a growth factor.
Claims 7 and 8 recite the limitation "the nanofibre layer" in line 3. There is insufficient antecedent basis for this limitation in the claim. No nanofibre layer is previously recited in the claims.
Claim 9 recites “wherein said aqueous NaOH solution of step e) is selected from the group consisting of laminin, fibronectin, collagen, RGD sequence, and proteoglycans so as to physically modify microscaffolds.” This claim is indefinite, because the recited components of the group are not a NaOH solution, and do not contain NaOH. As such, it is unclear how the aqueous NaOH solution is selected from one of these options. For the purposes of examination, NaOH is not deemed to be required in step (e).
Claim 10 recites step (g) “coating chemically modified, rinsed microscaffolds from step f)” (emphasis added). This claim is indefinite, because per claim 1, step f), the microscaffolds are not required to be chemically modified, but instead may be physically modified. As such, it is unclear if this step is required to be performed if physical modification in step f) is performed.
Further regarding claim 10, use of parentheses renders the claim indefinite because it is unclear whether the limitation within the parentheses is part of the claimed invention. Here, it is unclear if only one growth factor is required, or if multiple growth factors are required.
Claims 2 and 3 are included in this rejection, as these claims depend from above rejected claims and fails to remedy the noted deficiencies.
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 1-10 are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al. (Femtosecond laser ablation enhances cell infiltration into three-dimensional electrospun scaffolds, Acta Biomaterialia, Vol. 8, (2012), pp. 2648-2658 – Previously Presented), in view of McKean et al. (US 2019/0032007; Published 2019).
With regard to claims 1 and 2, Lee et al. teach an injectable biocompatible cell carrier in the form of a microscaffold (Abs.; Fig. 4-7), the microscaffold prepared by:
a) Preparing a solution comprising poly(L-lactinde) (PLLA), which is a polymer, and hexafluoroisopropanol (HFIP), which is a solvent (p. 2649, left col., 2.1 Fabrication of PLLA nanofibrous scaffolds).
b) Forming a fiber having a diameter ranging from 200 nm to 3l µm on a grounded collecting drum, which is a flat collector, by electrospinning to form a nonwoven fabric layer (p. 2649, left col., 2.1 Fabrication of PLLA nanofibrous scaffolds). Wherein it would have been obvious to one of ordinary skill in the art to electrospin fibers having diameters within the expressly taught range of 200 nm to 3l µm, which includes from 200 nm to 10 µm.
c) The nonwoven fabric layer having an approximate thickness of 130-200 µm (0.13-0.2 mm), which is fully encompassed within 0.01 and 0.2 mm, and laser cutting the nonwoven fabric layer formed on the collector into individual detachable microscaffolds of 0.5 cm x 0.5 cm squares (p. 2649, left col., 2.1. Fabrication of PLLA nanofibrous scaffolds; 2.2. Femtosecond laser ablation and characterization of ablated nanofibrous scaffolds; 2.3. Cell culture and in vitro cell experiments, para. 2).
d) The microscaffold is placed in a vacuum overnight following electrospinning (p. 2649, left col., 2.1. Fabrication of PLLA nanofibrous scaffolds), which is separating the microscaffold from the collector.
e) The microscaffold is coated with 1% fibronectin for 30 minutes, which is fully encompassed within 2-120 minutes (2.3. Cell culture and in vitro cell experiments, para. 2), wherein the 1% fibronectin coating solution is an aqueous protein solution. While it is not specifically noted that the microscaffold is “suspended” in the aqueous protein solution, it would have been obvious to one of ordinary skill in the art to coat the microscaffold in a way effective to achieve the desired coating, including suspending it in the fibronectin solution for the taught timeframe of 30 minutes, thus providing for the microscaffold to be coated as taught by Lee et al.
While a 1% fibronectin solution is about 1M, it would have been routine for an ordinary artisan to determine the most effective concentration for coating the microscaffold based on the intended downstream use. It is noted that "the discovery of an optimum value of a variable in a known process is usually obvious." Pfizer v. Apotex, 480 F.3d at 1368. The rationale for determining the optimal parameters for prior art result effective variables "flows from the 'normal desire of scientists or artisans to improve upon what is already generally known.'" Id. (quoting In re Peterson, 315 F.3d 1325, 1330 (Fed. Cir. 2003)). Accordingly, it would have been obvious to optimize the concentration of the fibronectin, including using 0.001-0.5 M, to result in a microscaffold coated with an effective amount of fibronectin for the intended downstream use, including for the specific cell type desired to be applied to the microscaffold, when practicing the taught method.
f) The microscaffold is washed with PBS following coating with the fibronectin solution (2.3. Cell culture and in vitro cell experiments, para. 2), which is rinsing excess protein from the microscaffold surface.
While Lee et al. teach laser cutting the nonwoven fabric layer into individual detachable microscaffolds, it is not taught that the microscaffolds have a cylindrical shape with a base diameter between 0.1 and 0.4 mm, or a prism with a base edge length between 0.04 and 0.4 mm.
McKean et al. teach an injectable biocompatible cell carrier in the form of a microscaffold, the microscaffold produced by electrospinning a solution comprising PLLA and HFIP to produce a nonwoven fibrous layer (Abs.; Ex. 1, para. 217). The nonwoven fibrous layer is laser cut into individual detachable microscaffolds having a cylindrical shape or a polygonal prism shape, the base diameter, including for the cylindrical shape, from 100-160µm (0.1-0.16 mm) or 110-150 µm (0.11-0.15 mm) (para. 66, 70-71), which are fully encompassed within 0.1 and 0.4 mm.
It would have been obvious to one of ordinary skill in the art to combine the teachings of Lee et al. and McKean et al., because both teach methods of producing an injectable biocompatible cell carrier in the form of a microscaffold, the microscaffold produced by electrospinning a solution comprising PLLA and HFIP to produce a nonwoven fibrous layer, where the nonwoven fibrous layer is laser cut into individual detachable microscaffolds having a shape. Laser cutting an electrospun nonwoven fibrous layer into individual detachable microscaffolds having a cylindrical shape or a polygonal prism shape, and a base diameter from 100-160µm (0.1-0.16 mm) or 110-150 µm (0.11-0.15 mm), is known in the art as taught by McKean et al. Shaping the electrospun nonwoven fibrous layer as produced by Lee et al. into a cylindrical or prism shape as taught by McKean et al. amounts to the simple substitution of one known microscaffold shape for another, and would have been expected to predictably and successfully provide for a microscaffold as desired by Lee et al. with an alternative shape.
With regard to claim 3, Lee et al. teach (b) forming a fiber having a diameter ranging from 200 nm to 3l µm on the collector (p. 2649, left col., 2.1 Fabrication of PLLA nanofibrous scaffolds). Wherein it would have been obvious to one of ordinary skill in the art to electrospin fibers having diameters within the expressly taught range of 200 nm to 3l µm, which includes from 200-1000 nm.
With regard to claim 4, Lee et al. teach that the collector is a grounded collector (p. 2649, left col., 2.1 Fabrication of PLLA nanofibrous scaffolds), which is a collector comprising a conductive material.
With regard to claim 5, McKean et al. teach that the polymer for electrospinning may include a blend of the polymer with an inorganic material, such as a magnetic nanoparticle (Para. 98), which is deemed to be an “active substance.” The rationale for the combination of McKean et al. with Lee et al. has been set forth previously. As such, a magnetic nanoparticle, which is an active substance, may be included in the solution comprising the polymer PLLA and solvent HFIP present in step (a) of the combined method.
While it is not specifically taught that the inorganic material, such as a magnetic nanoparticle, is present in an amount of ˂1% by weight of pure polymer, it would have been routine for an ordinary artisan to determine the most appropriate amount of the inorganic material, including a magnetic nanoparticle, for the composition of the microscaffold based on the intended downstream use. It is noted that "the discovery of an optimum value of a variable in a known process is usually obvious." Pfizer v. Apotex, 480 F.3d at 1368. The rationale for determining the optimal parameters for prior art result effective variables "flows from the 'normal desire of scientists or artisans to improve upon what is already generally known.'" Id. (quoting In re Peterson, 315 F.3d 1325, 1330 (Fed. Cir. 2003)). Accordingly, it would have been obvious to optimize the amount of the inorganic material, including a magnetic nanoparticle, including to ˂1% by weight of pure polymer, to result in a microscaffold with an effective amount of the inorganic material for the intended downstream use, including for the specific cell type desired to be applied to the microscaffold, when practicing the combined method.
With regard to claim 6, Lee et al. teach that the microscaffolds are placed in media including DMEM supplemented with 10% fetal bovine serum (FBS) (p. 2649, 2.3. Cell culture and in vitro cell experiments, para. 2), which includes growth factors including TGF and NGF (see Art of Record: Lee et al. 2022, Table 2). McKean et al. teach that the polymer for electrospinning may include a blend of the polymer with an inorganic material, such as a magnetic nanoparticle (Para. 98), which is deemed to be an “active substance.”
As McKean et al. teach that additional materials useful for downstream purposes may be included in the solution for electrospinning, it would have been obvious to one of ordinary skill in the art to include additional components desirable included in/on the microscaffolds of Lee et al. at an earlier stage in the production process, as taught by McKean et al. The rationale for the combination of McKean et al. with Lee et al. has been set forth previously.
With regard to claim 7, Lee et al. teach that the nonwoven fabric layer is cut using the beam of a femtosecond laser (Abs.).
With regard to claim 8, McKean et al. teach that the nonwoven fibrous layer is laser cut into individual detachable microscaffolds having a polygonal prism shape, the shape including a triangle, square, or rectangle (para. 159). The rationale for the combination of McKean et al. with Lee et al. has been set forth previously.
With regard to claim 9, Lee et al. teach that the microscaffold is coated with 1% fibronectin (2.3. Cell culture and in vitro cell experiments, para. 2), which is an aqueous NaOH solution consisting of fibronectin.
With regard to claim 10, Lee et al. teach that the rinsed microscaffolds are placed in media including DMEM supplemented with 10% fetal bovine serum (FBS) (p. 2649, 2.3. Cell culture and in vitro cell experiments, para. 2). As FBS includes growth factors (see Art of Record: Lee et al. 2022, Table 2), the rinsed, chemically modified microscaffolds are coated with a layer that includes growth factors.
Conclusion
No claims are allowable.
Art of Record:
Lee et al., Review of the Current Research on Fetal Bovine Serum and the Development of Cultured Meat, Food Science of Animal Resources, Vol. 42, No. 5, (2022), pp. 775-799 (FBS contains growth factors).
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/JENNIFER M.H. TICHY/Primary Examiner, Art Unit 1653
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