DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
The instant application is a divisional under 35 USC § 121 of US Application No. 17/184231, filed 24 February 2021 (now US Patent 12,178,943 B2, issued 31 December 2024). Acknowledgement is made of Applicant’s claim for benefit under 35 USC 119(e) to US Provisional Application No. 63016386, filed 28 April 2020.
Status of the Claims
Claims 1-20, of record 15 November 2024 are pending. Therefore, prosecution on the merits continues for claims 1-20.
Drawings
Acknowledgment is made of Applicant’s granted petition under 37 CFR 1.84(a)(2), filed 18 April 2025, for the colored drawings filed 15 November 2024.
Specification
The substitute Specification filed 23 January 2025 is acknowledged and entered into the application file.
Claim Objections
Claim 7 is objected to because of the following informalities:
Regarding claim 7: The instant claim is objected to for reciting “a psudounipolar nerve cell” in Line 2 instead of “a pseudounipolar nerve cell”.
Appropriate correction is required.
Claim Interpretation
In regard to the composition claims of the instant disclosure, it is noted that the use of a product for a particular purpose is not afforded patentable weight in a product claim where the body of the claim does not depend on the preamble for completeness but, instead, the structural limitations are able to stand alone. The MPEP states that, “.. in apparatus, article, and composition claims, the intended use must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art.” In re Casey, 152 USPQ 235 (CCPA 1967); In re Otto, 186 USPQ 458, 459 (CCPA 1963) (MPEP 2111.02). Therefore, the composition of the instant claims is interpreted as being drawn to the structural limitations recited in the claims. For instance, the intended use of the material – specifically that the composition is “for regeneration of skeletal muscle”– is not afforded patentable weight.
In addition, instant claim 11 recites that the composition in an injectable composition. This limitation is being treated as an intended use limitation. Intended use limitations are considered only in so far as they physically limit the claimed composition. Therefore, even if a composition of the prior art is not explicitly disclosed as being utilized for the recited applications, so long as the prior art composition is physically capable of being used for those applications – namely, being injected – it will thereby read on the claimed composition of instant claim 11.
Claim Rejections - 35 USC § 112
Claims 18 and 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.
Regarding claim 18: The instant claim recites the limitation "the aligned electrospun fiber scaffold" in Line 1. There is insufficient antecedent basis for this limitation in the claim, as there is no prior recitation of this limitation in the instant claim or parent claim 14. It is of note that the first recitation of an "aligned electrospun fiber scaffold" appears in instant claim 17.
Appropriate correction is required.
Regarding claim 20: The instant claim recites the limitation "the medical implant" in Line 1. There is insufficient antecedent basis for this limitation in the claim, as there is no prior recitation of this limitation in the instant claim or parent claim 14. It is of note that the recitation of “an implanted fiber scaffold" in parent claim 14 is not synonymous with the recitation of “medical implant” in instant claim 20, as a medical implant is more broad than an implanted fiber scaffold.
Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-11 are rejected under 35 U.S.C. 101 because the claimed invention is directed to nature-based product without significantly more.
Independent claim 1 is directed to a composition for regeneration of skeletal muscle, the composition comprising: a nerve cell secretome or an isolate thereof. It is of note that the intended use of the composition is not afforded patentable weight, as can be observed in the Claim Interpretation section above and is incorporated in its entirety herein.
The test for 101 eligibility of judicial exceptions can be found at MPEP § 2106:
“First, the claimed invention must be to one of the four statutory categories. 35 U.S.C. 101 defines the four categories of invention that Congress deemed to be the appropriate subject matter of a patent: processes, machines, manufactures and compositions of matter.”
“Second, the claimed invention also must qualify as patent-eligible subject matter, i.e., the claim must not be directed to a judicial exception unless the claim as a whole includes additional limitations amounting to significantly more than the exception. The judicial exceptions (also called "judicially recognized exceptions" or simply "exceptions") are subject matter that the courts have found to be outside of, or exceptions to, the four statutory categories of invention, and are limited to abstract ideas, laws of nature and natural phenomena (including products of nature). Alice Corp. Pty. Ltd. v. CLS Bank Int'l, 573 U.S. 208, 216, 110 USPQ2d 1976, 1980 (2014) (citing Ass'n for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 589, 106 USPQ2d 1972, 1979 (2013).”
“The Supreme Court in Mayo laid out a framework for determining whether an applicant is seeking to patent a judicial exception itself, or a patent-eligible application of the judicial exception. See Alice Corp., 573 U.S. at 217-18, 110 USPQ2d at 1981 (citing Mayo, 566 U.S. 66, 101 USPQ2d 1961). This framework, which is referred to as the Mayo test or the Alice/Mayo test, is discussed in further detail in subsection III, below. The first part of the Mayo test is to determine whether the claims are directed to an abstract idea, a law of nature or a natural phenomenon (i.e., a judicial exception). Id. If the claims are directed to a judicial exception, the second part of the Mayo test is to determine whether the claim recites additional elements that amount to significantly more than the judicial exception. Id. citing Mayo, 566 U.S. at 72-73, 101 USPQ2d at 1966). The Supreme Court has described the second part of the test as the "search for an 'inventive concept'". Alice Corp., 573 U.S. at 217-18, 110 USPQ2d at 1981 (citing Mayo, 566 U.S. at 72-73, 101 USPQ2d at 1966).”
Examiners should determine whether a claim satisfies the criteria for subject matter eligibility by evaluating the following steps outlined in a flow chart at MPEP 2106(III) and 2106.04(II)(A):
Step 1: is the Claim to a process, machine, manufacture or composition of matter? If Yes, proceed to Step 2A;
Step 2A, prong one: Is the Claim directed to a law of nature, a natural phenomenon (product of nature), or an abstract idea? If Yes, proceed to Step 2A, prong two;
Step 2A, prong two: Does the claim recite additional elements that integrate the judicial exception into a practical application? If No, proceed to Step 2B;
Step 2B: Does the claim recite additional elements that amount to significantly more (an inventive concept) than the judicial exception? If No, the claim is not eligible subject matter under 35 USC 101.
With regard to Step 1: YES, the claims are directed to a composition of matter, or product.
With regard to Step 2A, prong one: YES, the claims are directed to a nerve cell secretome or isolate thereof, which are nature-based products. More specifically, the claimed nerve cell secretome or isolate thereof are compared to the closest naturally occurring counterpart, which is a nerve cell secretome or isolate thereof, per se. Thus, there is no marked different between the claims and products of nature. See, for example, Pages 3158, 3165-3166 and Supplementary Table 5 of Kuhn et al (The EMBO Journal, 2012).
With regard to Step 2A, prong two: No, the claims do not include any additional elements that integrate the judicial exceptions into a practical application. Integration into a practical application requires additional elements in the claim to apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception, such that the claim is more than a drafting effort designed to monopolize the exception.
The claims do not modify or transform the naturally occurring nerve cells, nor apply the nerve cell secretome towards a particular treatment or medical condition, nor impose a meaningful limit on the nerve cell secretome recited therein.
With regard to Step 2B: No, the claims do not provide any additional elements that amount to significantly more (an inventive concept) than the judicial exception.
Taken together, the claims encompass a natural product. The judicial exception is not integrated into practical applications as iterated above. The claims do not include additional elements
that are sufficient to amount to significantly more than the judicial exception as iterated above.
Claims 2-11 are included in the rejection because they fully incorporate the limitations of rejected claim 1 and fail to provide any additional elements that are sufficient to amount to significantly more than the judicial exception or integrate the judicial exception into a practical application.
Claim Rejections - 35 USC § 102
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 (i.e., changing from AIA to pre-AIA ) 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.
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 1, 4-6, and 10-11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kuhn et al (The EMBO Journal, 2012).
Kuhn et al disclose a nerve cell secretome isolate comprising Glypican-1, Prosaposin, and Cathepsin B (Pages 3158, 3164-3166; Figure 1; Supplementary Table 5). Kuhn et al further disclose that the nerve cell secretome isolate is from the culture of 40 million nerve cells in 20 mL of culture media – or at a concentration of 2 x 107 nerve cells per 10 mL of culture media (Page 3166).
Accordingly, Kuhn et al anticipate the claims as follows:
Regarding claims 1 and 4-6: Kuhn et al disclose a nerve cell secretome isolate (claim 5) comprising Glypican-1, Prosaposin, and Cathepsin B (claims 4, 6). This therefore reads on the composition of instant claim 1.
Regarding claim 10: Following the discussion of claim 1, Kuhn et al further disclose that the nerve cell secretome is a secretome from the culture of nerve cells at a concentration of 2 x 107 nerve cells per 10 mL of culture media. This therefore reads on the composition of the instant claim. See MPEP § 2131.03(I).
Regarding claim 11: Following the discussion of claim 1, Kuhn et al further disclose that the nerve cell secretome is produced from the culture of nerve cells in culture media. As the nerve cell secretome is comprised within a liquid product that is capable of being injected, this therefore reads on the composition of the instant claim. See Claim Interpretation section above.
Claims 1-3, 7-8, 12-17, and 20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Das et al (bioRxiv, 2019) as evidenced by Nanofiber Solutions LLC (Products Informational Sheet, 2026) and Nishimaru et al (PNAS, 2005).
Das et al disclose a method for regenerating skeletal muscle, wherein motor neurons and skeletal muscle myoblasts are co-cultured on an aligned polymeric electrospun fiber mat and subsequently implanted into a subject in need thereof (Abstract; Pages 1, 5-15, 18-20; Figures 2-3, 9; Nanofiber Solutions LLC: Page 1). Das et al further disclose that the seeded motor neurons secrete agrin, which allows for the formation of neuromuscular junctions between the motor neurons and skeletal muscle myoblasts, as well as neurotrophic factors including BDNF (Pages 14-16). Das et al further disclose that the pre-innervation of the fiber mats with motor neurons and skeletal muscle myoblasts allows for an increased microvasculature and promotion of mature neuromuscular junctions near the injury area, thus promoting the regeneration of skeletal muscle (Pages 8-17).
Accordingly, Das et al anticipate the claims as follows:
Regarding claims 1, 12-17, and 20: Das et al disclose a method of regenerating skeletal muscle, wherein motor neurons and skeletal muscle myoblasts are co-cultured (claim 20) on an aligned electrospun polymeric fiber mat (claims 15-17) that is subsequently implanted into a subject in need thereof. As the motor neurons cultured within the implanted fiber mat release secreted proteins – or the secretome (claim 1) – to the skeletal muscle myoblasts (claim 13) such that the motor neuron secretome is adjacent to the implanted fiber mat (claim 14), this therefore renders obvious the method of instant claim 12.
Regarding claims 2-3: As aforementioned in the discussion of claim 1, Das et al disclose that the neuron secretome allows for the formation of neuromuscular junctions between the neurons and skeletal muscle myoblasts (claim 2), which ultimately promotes the regeneration of skeletal muscle (claim 3). This therefore reads on the compositions of the instant claims.
Regarding claims 7-8: The term, “catecholamine,” is interpreted consistent with the broadest reasonable interpretation of the term as would be understood by a person having ordinary skill in the art as a group of neurotransmitters including acetylcholine, dopamine, epinephrine, and norepinephrine among others.
Accordingly, as aforementioned in the discussion of claim 1, Das et al disclose that motor neurons are seeded onto the fiber mat. As motor neurons release acetylcholine and are thus inherently catecholamine nerve cells (Nishimaru et al: Pages 5247-5249), this therefore reads on the composition of the instant claim. See MPEP § 2112.
Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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.
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 1-3, 7-9, and 12-20 are rejected under 35 U.S.C. 103 as being unpatentable over Takeda (JP 2018/196370 A, translation provided by Global Dossier) in view of Das et al (bioRxiv, 2019) as evidenced by Westerink et al (Acta Physiol, 2008, of record on IDS filed 15 November 2024).
Takeda et al is considered prior art under 35 USC 102(a)(1). Das et al is considered prior art under 35 USC 102(a)(1).
Regarding claims 1, 12-14, 16-17, and 20: Takeda et al disclose an implanted electrospun fiber mat seeded with neurons or skeletal muscle myoblasts for the regeneration of tissue (Paragraphs [0008], [0013], [0017]-[0020], [0028]-[0037], [0040], [0042], [0045]-[0046]).
Takeda et al further disclose that the neurons can be primary cells or from an established cell line (Paragraphs [0031], [0040]).
Takeda et al do not disclose that the neurons and skeletal muscle myoblasts are cultured on the electrospun fiber mat together, nor that the neuron secretome is applied adjacent to the skeletal muscle myoblasts, as required by instant claim 12.
Das et al, however, disclose a method for regenerating skeletal muscle, wherein neurons and skeletal muscle myoblasts are co-cultured on an aligned fiber mat and subsequently implanted into a subject in need thereof (Abstract; Pages 1, 5-11, 13-15, 18-20; Figures 2-3, 9). Das et al further disclose that the seeded neurons secrete agrin, which allows for the formation of neuromuscular junctions between the neurons and skeletal muscle myoblasts, as well as neurotrophic factors including BDNF (Pages 14-16).
Therefore, it would have been prima facie obvious to have modified the method of Takeda et al such that the neurons and skeletal muscle myoblasts are co-cultured on an aligned fiber mat for the regeneration of skeletal muscle, as detailed in Das et al. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to pre-innervate the fiber mat comprising skeletal muscle myoblasts, as it allows for an increased microvasculature and promotion of mature neuromuscular junctions near the injury area (Das et al: Pages 8-17), and would have had a reasonable expectation of success given that the disclosures of Takeda et al and Das et al are concerned with the culture of neurons and skeletal muscle myoblasts on fiber mats for the regeneration of tissue. See MPEP § 2143(I)(G).
Consequently, Takeda et al as modified by Das et al render obvious a method of regenerating skeletal muscle, wherein neurons and skeletal muscle myoblasts are co-cultured (claim 20) on an aligned electrospun fiber mat (claims 16-17) that is subsequently implanted into a subject in need thereof. As the neurons cultured within the implanted fiber mat release secreted proteins – or the secretome (claim 1) – to the skeletal muscle myoblasts (claim 13) such that the neuron secretome is adjacent to the implanted fiber mat (claim 14), this therefore renders obvious the method of instant claim 12.
Regarding claims 2-3: As aforementioned in the discussion of claim 1, Das et al disclose that the neuron secretome allows for the formation of neuromuscular junctions between the neurons and skeletal muscle myoblasts (claim 2), which ultimately promotes the regeneration of skeletal muscle (claim 3). This therefore renders obvious the compositions of the instant claims for the same reasons as discussed in the rejection of instant claim 1.
Regarding claims 7-9: Following the discussion of claim 1, Takeda et al further disclose that the neurons are PC12 nerve cells (claim 9) (Paragraphs [0031], [0040]). As PC12 nerve cells are inherently catecholamine nerve cells (claims 7-8) (Westerink et al: Pages 2-3, 6-10), this therefore reads on the composition of the instant claims.
Regarding claims 15 and 19: Following the discussion of claim 14, Takeda et al further disclose that the electrospun fibers are polymeric fibers (claim 15) comprised of tissue culture polystyrene (claim 19) (Paragraphs [0012], [0016], [0024], [0027]). This therefore reads on the methods of the instant claims.
Regarding claim 18: Following the discussion of claim 14, Takeda et al further disclose that the electrospun fiber mat is formed by collecting the electrospun fibers on a rotating drum (Paragraph [0050]). This therefore reads on the method of the instant claim.
Conclusion
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/ALYSSA G WESTON/Examiner, Art Unit 1633
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