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 .
Claim Status
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 13 January, 2026 has been entered.
Claims 1, 3, 5-7, and 9-13 were previously pending.
Receipt is acknowledged of the amendments to the claims filed on 13 January, 2026. Claim 1 is amended. Claim 7 is cancelled.
Therefore, claims 1, 3, 5-6, and 9-13 are pending and are the subject of the present Official Action.
Priority
The present application is a 35 U.S.C. 371 national stage filing of International Application No. PCT/KR2020/018767, filed 21 December, 2020.
The earliest possible priority for the instant application is 21 December, 2020.
Withdrawn Rejections/Objections in view of Applicant’s Amendments/Arguments
Claim Rejections - 35 USC § 103
The rejection of claims 1, 3, 5-7, and 9-13 under 35 U.S.C. 103 as being unpatentable over McCrary et al. (Tissue Engineering Part C: Methods 26.1 (Published Online: January, 2020): 23-36., hereinafter “McCrary”), Hudson et al. (Tissue engineering 10.9-10 (2004): 1346-1358., hereinafter “Hudson”), Wüthrich et al. (Materials Science and Engineering: C 117 (published online: August, 2020): 111311., hereinafter “Wuthrich”), ResearchGate_NaOH (https://www.researchgate.net/post/How-to-change-the-pH-of-PBS-to-pH9-and-pH11, accessed: 25 April, 2025, hereinafter “ResearchGate”), Moore (Current Protocols in Molecular Biology 35.1 (1996): A-2., hereinafter “Moore”), Price et al. (Tissue Engineering Part C: Methods 21.1 (2015): 94-103., hereinafter “Price”), Willemse et al. (Materials Science and Engineering C 108 (Published online: September, 2019), hereinafter “Willemse”), Choudhury et al. (Acta biomaterialia 115 (published online: August, 2020): 51-59., hereinafter “Choudhury”), and Kajbafzadeh et al. (Tissue Engineering Part C: Methods 19.8 (2013): 642-651., hereinafter “Kajbafzadeh”) is withdrawn in view of Applicant’s amendments to the claims.
Applicant has amended claim 1 to require an anionic surfactant solution that is free of a basic component. None of the cited references teach or suggest such a solution.
New Rejections Necessitated by Applicant’s Amendments to the Claims
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 3, 5-6, and 9-13 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of manufacturing a decellularized nerve graft comprising: providing a nervous tissue; a) removing a lipid component of the nervous tissue, thereby providing lipid component- removed nervous tissue; and b) removing cells from the lipid component-removed nervous tissue, wherein b) is performed by treating the lipid component-removed nervous tissue with NaOH at 0.1N to 2N followed by treatment with 2% to 4% SDC “solution”; in b), the time for treatment with the basic solution is 30 minutes to 9 hours, and the time for treatment with the anionic surfactant solution is 30 minutes to 9 hours; and a) and b) are performed using a peristaltic pump system operated at 50 to 300 rpm (revolutions per minute) and does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the patent coupled with information known in the art without undue experimentation (United States v. Telectronics, Inc., 8 USPQ2d 1217 (Fed. Cir. 1988)). Whether undue experimentation is required is not based on a single factor but is rather a conclusion reached by weighing many factors (See Ex parte Forman, 230 USPQ 546 (Bd. Pat. App. & Inter, 1986) and In re Wands, 8USPQ2d 1400 (Fed. Cir. 1988); these factors include the following:
1) Nature of invention. The instant claims are drawn to method of manufacturing a decellularized nerve graft, comprising a step of treating a lipid component-removed nervous tissue with an anionic surfactant solution that is free of a basic component.
2) Scope of the invention. The scope of the invention is broad insofar as it encompasses any anionic surfactant in any solution so long as it is free of any basic component. The specification does not define “basic component”. Therefore, amended claim 1 encompasses a solution completely devoid of anything that can be considered a “basic component”. It is noted that, as written, the claimed solution encompasses solutions somehow lacking the fundamental principal of acid-base equilibrium. Even pure H2O in solution has some amount of H3O+ (acid) and OH- (base or “basic component”) (See “Acid-Base Equilibria”, https://christou.chem.ufl.edu/wp-content/uploads/sites/62/2017/01/Chapter-18-Acids-and-Bases-Week-1.pdf, accessed: 27 January, 2026).
3) Number of working examples and guidance. The specification teaches only one example of a method of manufacturing a decellularized nerve graft, comprising a step of treating a lipid component-removed nervous tissue with an anionic surfactant solution. In this example, sodium deoxycholate is the anionic surfactant and there is no teaching of what else is comprised in the “solution” (Specification, page 18, lined 9-11; Table 1). The single example teaches that treatment of a nervous tissue with NaOH at 0.1N to 2N followed by treatment with 2% to 4% SDC “solution” achieved “high decellularization efficiency” (Specification, page 18, lines 9-11; Table 1). No other working example is provided using anything other than SDC as the anionic surfactant.
4) State of the art. The use of SDC to decellularize nervous tissue is well known in the art (See McCrary et al., and Hudson et al. (both of record)). McCrary et al. (Tissue Engineering Part C: Methods 26.1 (Published Online: January, 2020): 23-36., hereinafter “McCrary”) teaches a method of decellularizing a peripheral nerve comprising washing the nerve repeatedly in a solution containing 5% w/v, 3% w/v, or 1% w/v sodium deoxycholate (SDC) and PBS (McCrary, page 24, last partial paragraph, Abstract, Table 1). Hudson et al. (Tissue engineering 10.9-10 (2004): 1346-1358., hereinafter “Hudson”) also teaches a method of decellularizing nervous tissue using sodium deoxycholate in PBS solutions (Hudson, page 1348, fourth full paragraph). Hudson goes further to teach other anionic detergents but even these detergents (SB-10, sodium caprylate) were maintained in PBS at a basic pH (Hudson, page 1348, fourth full paragraph). Therefore, the art at the time of filing taught several anionic detergent solutions (including SDC solutions) for the decellularization of nervous tissue.
5) Unpredictability of the art. McCrary and Hudson together teach methods of decellularizing nervous tissue using SDC in PBS (see above). Hudson specifically teaches that a higher pH (7.8-8.2) is required to maintain the solubility of SDC in PBS (Hudson, page 1348, fourth full paragraph). Even the other anionic detergents of Hudson were maintained at a basic pH (Hudson, page 1348, fourth full paragraph). The language “free of a basic component” precludes PBS and even water because both of these solutions (and all others in which an anionic solute is present) possess the fundamental characteristics of acid-base equilibria (see above). The Chemical book website (Sodium deoxycholate CAS#: 302-95-4, accessed 26 January, 2026, hereinafter “Chemicalbook”) teaches that sodium deoxycholate (SDC) itself has a pH of 7.5-9.0 when dissolved in water (Chemicalbook, “PH”). Further, Sigma teaches that a gradual reduction of the pH of a solution containing SDC to around 5 results in precipitation of the SDC out of solution (Sigma-Aldrich, Product Information, Sodium deoxycholate monohydrate, “Preparation Instructions”). Therefore, a skilled artisan at the time of filing knew that SDC was typically dissolved in PBS for decellularizing applications and that doing so necessarily required a basic component either explicitly to maintain solubility of the SDC or implicitly via fundamental acid-base equilibrium principles. Even where SDC is taught as being able to be dissolved in a solution with a pH less than 7 (acidic), such solutions can only be as low as pH 5 to maintain SDC in the solution. Further, with regard to anionic detergents more generally, the skilled artisan knew from the teachings of Hudson that these were typically used in solutions of PBS at a basic pH.
The “predictability or lack thereof” in the art refers to the ability of one skilled in the art to extrapolate the disclosed or known results to the claimed invention. If one skilled in the art can readily anticipate the effect of a change within the subject matter to which the claimed invention pertains, then there is predictability in the art. On the other hand, if one skilled in the art cannot readily anticipate the effect of a change within the subject matter to which that claimed invention pertains, then there is lack of predictability in the art. Accordingly, what is known in the art provides evidence as to the question of predictability M.P.E.P. § 2164.03.
As well, the claims are drawn to an incredibly large genus of methods of manufacturing decellularized nerve grafts utilizing any anionic surfactant in any solution that is free of any possible basic component. As discussed above, such a solution is an impossibility since every possible solution will necessarily possess some base because of the fundamental principle of acid-base equilibria (see Acid-Base Equilibria, first three pages). In cases involving predictable factors, such as mechanical or electrical elements, a single embodiment provides broad enablement in the sense that, once imagined, other embodiments can be made without difficulty and their performance characteristics predicted by resort to known scientific laws. In cases involving unpredictable factors, such as most chemical reactions and biological activity, the scope of enablement varies inversely with the degree of unpredictability of the factors involved. To this end, the specification discloses only NaOH at 0.1N to 2N followed by treatment with 2% to 4% SDC “solution” achieved “high decellularization efficiency” and have not provided sufficient nexus between the structure and the required function.
This raises issues under description as well as enablement. The description component of the rejection is herein included as you cannot use what you have not described. Furthermore, the enablement of the instant invention has been assessed in light of the specification and the prior art available at the time of filing. "However, claims reading on significant numbers of inoperative embodiments would render claims non-enabled when the specification does not clearly identify the operative embodiments and undue experimentation is involved in determining those that are operative. Atlas Powder Co. v. E.I. duPont de Nemours & Co., 750 F.2d 1569, 1577, 224 USPQ 409, 414 (Fed. Cir. 1984); In re Cook, 439 F.2d 730, 735, 169 USPQ 298,302 (CCPA 1971). (see MPEP 2164.08(b). The claims read on solutions somehow lacking fundamental acid-base equilibria which the art recognizes as characteristic of all solutions including pure water. Thus, the claims read on a significant number of inoperative embodiments in encompassing any anionic surfactant and any solution that is completely free of any basic component. Even further, the specification only exemplifies one anionic surfactant solution with no description of what else the “solution” comprises and no description of how said solution is “free of a basic component”. The claims lack adequate description to link structure to the required functions. The Court indicated that while applicants are not required to disclose every species encompassed by a genus, the description of a genus is achieved by the recitation of a precise definition of a representative number of members of the genus, such as by reciting the structure. Structural features that could distinguish the compounds of the claimed genus from others not encompassed by the genus are missing from the disclosure. In this case, there are specific elements referenced but the claims reference these structures with broad generic functional terms that represent a large and diverse genus of elements.
6) Amount of Experimentation Required. The claims have been evaluated in light of the art at the time of filing and found not to be commensurate in scope with the specification. MPEP 2164.05 teaches, “However, the examiner should carefully compare the steps, materials, and conditions used in the experiments of the declaration with those disclosed in the application to make sure that they are commensurate in scope; i.e., that the experiments used the guidance in the specification as filed and what was well known to one of skill in the art. Such a showing also must be commensurate with the scope of the claimed invention, i.e., must bear a reasonable correlation to the scope of the claimed invention.”
Consequently, the prior art (and post-filing art) when combined with the teaching of only a single method of manufacturing a decellularized nerve graft using SDC solution, shows that one of skill in the art at the time the invention was made would have had no basis to reasonably predict or conclude the claimed methods of manufacturing could be identified given the lack of details necessary to identify those meeting the necessary functions for all possible anionic surfactant solutions free of a basic component. Though not controlling, the lack of working examples, is, nevertheless, a factor to be considered. When a patent applicant chooses to forego exemplification and bases utility on broad terminology and general allegations, he runs the risk that unless one with ordinary skill in the art would accept the allegations as obviously valid and correct, the PTO may, properly, ask for evidence to substantiate them. Ex parte Sudilovsky, 21 USPQ2d 1702, 1705 (BPAI 1991); In re Novak, 134 USPA 335 (CCPA 1962); In re Fouche, 169 USPQ 429 (CCPA 1971).
Given the anionic surfactant solutions taught in the art relative to the very broad methods that are claimed, the description of only a single working example of an anionic surfactant solution in which no other details for the solution are described, the level of unpredictability embodied in the species encompassed by the genus claimed, and the amount of experimentation required to determine the operable species, it would require undue experimentation to use the invention commensurate in scope with the claims. Further, in an unpredictable art, the disclosure of limited examples (only a single working example of an anionic surfactant solution in which no other details for the solution are described) would represent to the skilled artisan that applicants were not in possession of claimed genus of anionic surfactant solutions free of a basic component.
Examiner’s Comment
The amendments to the claims necessitated withdrawal of the prior art rejections while simultaneously necessitating new rejections under 35 U.S.C. 112(a). It is noted that, were Applicant solely to return the claims to their prior state, the previously-issued prior art rejections would likely be applied again upon the withdrawal of the 112(a) rejections.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRENDAN THOMAS TINSLEY whose telephone number is (703)756-5906. The examiner can normally be reached Mon-Fri 8:00-5:00.
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/BRENDAN THOMAS TINSLEY/Examiner, Art Unit 1634
/MARIA MARVICH/Primary Examiner, Art Unit 1634