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 .
Status of Application, Amendments and/or Claims
The amendment and Applicant’s arguments, filed 02 March 2026, have been entered in full. Claims 3, 4, 12, 13, 16, 17, 21 and 22 are canceled. Claims 1, 5-9, 11, 14, 15, 18-20 are amended. Claims 1, 2, 5-11, 14, 15, 18-20 are under examination.
Information Disclosure Statement
The information disclosure statement(s) (IDS) (filed 02 March 2026) was received and complies with the provisions of 37 CFR §§1.97, 1.98 and MPEP § 609. It has been placed in the application file and the information referred to therein has been considered as to the merits.
Withdrawn Objections And/Or Rejections
The objection to the claims 3, 4, 12, 13, 16 and 17, as set forth at page 3 of the previous Office Action (03 November 2025), is withdrawn in view of the amendment (02 March 2026).
The rejection to claims 1-20 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ),
second paragraph, as set forth at page 4 of the previous Office Action (03 November 2025), is withdrawn in view of the amendment (02 March 2026).
The rejection to claims 9-14 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, scope of enablement, as set forth at pages 4-6 of the previous Office Action (03 November 2025), is withdrawn in view of the amendment (02 March 2026).
The rejection to claims 1, 2, 6-10, 15, 19 and 20 under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Wu et al. (THE REAGENTS OF THE UNIVERSITY OF CALIFORNIA, WO 2012/170452, published 13 December 2012), as set forth at pages 6-8 of the previous Office Action (03 November 2025), is withdrawn in view of the amendment (02 March 2026).
The rejection to claims 1, 9 and 11 under 35 U.S.C. 102(a1) as being anticipated
by Capsoni et al. (Intranasal "painless" Human Nerve Growth Factors Slows Amyloid
Neurodegeneration and Prevents Memory Deficits in App X PS1 Mice. PloS ONE Volume 7, Issue 5: e37555, pages 1-16; May 2012), as set forth at pages 9-10 of the previous Office Action (03 November 2025), is withdrawn in view of the amendment (02 March 2026).
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.
1. Claims 1, 2, 6-10, 15, 19 and 20 remain rejected under 35 U.S.C. 103 as being unpatentable over Wu et al. (WO 2012/170452, published 13 December 2012) in view of Desai et al. (US 2007/0249044; published Oct. 25 2007).
The basis for this rejection is set forth at pages 10-12 of the previous Office Action (03 November 2025).
APPLICANT’S ARGUMENTS: Applicant cites case law. Applicant argues that the combination of Wu and Desai does not disclose let alone teach the recited features. Applicant states that as noted on page 11 of the previous Office Action, regarding the teachings of Desai, the three-dimensional cell culture matrix is "suspended in the cell culture gel, wherein the gel comprises growth factors, such as a NGF (paras 0011, 0012, 0015)."
Applicant argues that the function of NGF in Desai is to enhance the growth of the cell culture and by no means would a person of skill in the art reasonably interpret NGF as a viable species of a "drug, peptide, protein, or nucleic acid" to be incorporated into the "microrods or other microstructures". Applicant further argues that Desai is referring to a wild-type NGF sequence. Applicant argues that there is no mention in Desai of the term "mutant," let alone providing a mutated NGF incorporated with nanorods or microrods for the effect of reducing pain in a subject in need thereof. Applicant argues that the term "pain" is not mentioned anywhere in Desai and therefore it is unclear why a person of skill would reasonably understand the teachings of Wu and Desai to be compatible.
Applicant maintains that by comparison, and as taught by the present application, prior attempts to administer wild-type NGF to humans induced intolerable pain. Attempts to mitigate the pain effects associated with delivering wild-type NGF, for example by reducing dosages thereof, led to loss of the clinical benefits of NGF. Applicant directs the Examiner’s attention to the instant specification at paragraph [0004] on page 2 in the "Background of the Invention". Applicant asserts that there is no consideration of this profound limitation of wild-type NGF in the disclosure of Desai.
Applicant argues that at most, the Examiner has identified the various parts of the claimed invention, but has not provided any scientifically credible evidence as to an apparent reason for one of skill in the art to provide a composition comprising a therapeutically effective amount of a nerve growth factor (NGF) mutant that does not elicit pain, wherein the composition comprises micro-rods or nano- rods that deliver the NGF mutant, and thereby, administer thereof to a subject in need thereof for the treatment of neuropathy and/or pain. Applicant submits that the Examiner has merely alleged that Wu and Desai provide the elements of the claim and that the teachings therein could be combined. Applicant argues that the mere fact that two elements can theoretically be combined does not necessarily mean that it would be obvious to one of ordinary skill in the art to actually combine them. Applicant directs the Examiner’s attention to In re Mills, 916 F.2d 680 (Fed. Cir. 1990) (stating that it is not sufficient to simply cite references that are capable of being combined to establish the prima facie case of obviousness); KSR at 1741 ("a patent composed of several elements is not proved obvious merely by demonstrating that each of its elements was, independently, known in the prior art"). Applicant submits that the claimed combination was not taught or suggested by the cited prior art, and it was only with the benefit of improper hindsight reasoning after review of the disclosure of the present disclosure that a rejection was formulated.
Applicant respectfully reminds the Examiner that "a prior art reference must be considered in its entirety, i.e., as a whole, including portions that would lead away from the claimed invention. (W.L. Gore & Associates, Inc. v. Garlock, Inc., 721 F.2d 1540 (Fed. Cir. 1983)) and that "[i]t is improper to combine references where the references teach away from their combination. (In re Grasselli, 713 F.2d 731, 743 (Fed. Cir. 1983)). Applicant argues that the combination of Wu and Desai cannot account for all the features of the present claims individually and there would be no motivation to combine the teachings
Applicant’s arguments have been fully considered but are not found persuasive for the following reasons:
a. The Wu reference already teaches a pharmaceutical composition comprising a nerve growth factor (NGF) mutant (i.e., R100W), which has the biological function of treating neuropathy diseases without eliciting pain associated with NGF treatment. Wu teaches methods comprising administering the NGF mutant for improvement in any aspect of pain including lessening severity, alleviation of one or more symptoms associated with a neurodegenerative disease or disorder. Wu teaches a method for treating neuropathy or treating pain induced by a treatment with an NGF that elicits pain comprising administering the NGF mutant (i.e., R100W) to a human subject.
Wu teaches the background on how treatment with exogenous wildtype NGF has been shown to lead to an increase in pain and pain sensitivity.
Contrary to the presented arguments, there is no need for Desai to teach a mutant NGF or pain associated with administered wildtype NGF, because Wu teaches all of this. The only thing Wu does not teach is using micro-rods or nano-rods to deliver the already taught pharmaceutical composition comprising nerve growth factor (NGF) mutant (R100W).
b. Applicant argues that the function of NGF in Desai is to enhance the growth of the cell culture and by no means would a person of skill in the art reasonably interpret NGF as a viable species of a "drug, peptide, protein, or nucleic acid" to be incorporated into the "microrods or other microstructures".
This argument is not found persuasive. Desai et al. teach a three-dimensional cell culture matrix comprising composite of a cell culture gel and polymeric microstructures suspended in the cell culture gel (para 0011). Desai et al. teach the microstructures further comprise agents that facilitate cell adhesion and/or growth such as nerve growth factor (para 0015). Desai et al. teach that the microstructure has encapsulated an agent, for example, a drug, therapeutic peptide, nucleic acid, dye and the like, to be delivered to a target site in vivo (para 0016). Desai et al. teach microrods as the microstructures (para 0017). Desai et al. teach the microrods or other microstructures are prepared so as to have incorporated therein a drug, peptide, protein, or nucleic acid that can be released at a target site in a controlled release manner. Desai et al. teach that in certain embodiments, the microrods or microstructures have incorporated therein an agent for delivery to the stressed heart in order to prevent myocyte cell death and improve cardiac function. Desai et al. teach that an exemplary such agent may be Insulin-like Growth Factor 1 (IGF-1) or mechano-growth factor, MGF (0049).
Contrary to the presented arguments, Desai et al. teach incorporating nerve growth factor (NGF) and other growth factors such as IGF-1 or MGF into microrods.
c. One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
In the instant case, employing microrods (as taught by Desai) would be another route of targeted delivery of an NGF mutant (R100W) that is useful for treating a neuropathy and treating pain induced by treatment with an NGF that elicits pain (as taught by Wu).
The scientific reasoning and evidence as a whole indicate that the rejection should be maintained.
2. Claims 1, 2, 5-10, 14, 15, 18-20 remain rejected under 35 U.S.C. 103 as being unpatentable over Wu et al. (WO 2012/170452, published 13 December 2012) in view of Desai et al. (US 2007/0282247; published Dec. 6 2007) and Keeney et al. (J Mater Chem B Mater Biol Med 3(45):8757-8770; 2015).
The basis for this rejection is set forth at pages 12-15 of the previous Office Action (03 November 2025).
APPLICANT’S ARGUMENTS: Applicant reiterates the remarks previously made for claims 1, 2, 6-10, 15, 19, and 20 over the combination of Wu and Desai. Applicant argues that to cure the missing teachings of Wu and Desai, the Examiner cites Keeney. Applicant maintains that here is no teaching nor suggestion from the combination of Wu, Desai, and Keeney, that provides the requisite motivation to a person of skill in the art to arrive at the claimed methods for treating neuropathy and pain comprising administering to a subject in need thereof a composition comprising a therapeutically effective amount of an NGF mutant that does not elicit pain, wherein the composition comprises micro-rods or nano-rods that deliver the NGF mutant, and they would have no expectation of success.
Applicant argues that Keeney allegedly discloses layer-by-layer (LbL) techniques for drug delivery. Applicant notes that Keeney is wholly silent regarding NGF mutants, let alone those NGF mutants that do not elicit pain for the treatment of subjects in need thereof, much less methods for treating neuropathy and pain comprising administering to a subject in need thereof a composition comprising a therapeutically effective amount of an NGF mutant that does not elicit pain, wherein the composition comprises micro-rods or nano-rods that deliver NGF mutants, as required by the pending claims.
Applicant’s arguments have been fully considered but are not found persuasive for the reasons discussed above regarding claims 1, 2, 6-10, 15, 19, and 20 and for reasons of record. The scientific reasoning and evidence as a whole indicate that the rejection should be maintained.
3. Claims 1, 9 and 11 remain rejected under 35 U.S.C. 103 as being unpatentable over Capsoni et al. (PloS ONE Volume 7, Issue 5: e37555, pages 1-16; May 2012) in view of Desai et al. (US 2007/0282247; published Dec. 6 2007).
The basis for this rejection is set forth at pages 15-17 of the previous Office Action (03 November 2025).
APPLICANT’S ARGUMENTS: Applicant reiterates the remarks previously made for claims 1, 2, 6-10, 15, 19, and 20 over the combination of Wu and Desai, and asserts that Capsoni suffers from the same missing teachings as that of cited reference Wu. Applicant argues that Desai does not cure the missing teachings of Capsoni for at least the same reasons as provided previously. Applicant argues that there is no teaching nor suggestion from the combination of Capsoni and Desai that provides the requisite motivation to a person of skill in the art to arrive at the claimed compositions and methods for treating neuropathy and pain comprising administering to a subject in need thereof a composition comprising a therapeutically effective amount of an NGF mutant that does not elicit pain, wherein the composition comprises micro-rods or nano-rods that deliver the NGF mutant, and they would have no expectation of success.
Applicant’s arguments have been fully considered but are not found persuasive for the reasons discussed above regarding claims 1, 2, 6-10, 15, 19, and 20. In addition, Capsoni et al. teach NGF mutants NGFR100W, NGFR100E and a double mutant of human NGFP61S/R100E.Capsoni et al. teach that these NGF mutants have less pain-inducing actions. Capsoni et al. teach that the anti-neurodegenerative properties of hNGFP61S/R100E protein were assessed in a disease-relevant primary neuron model.
The scientific reasoning and evidence as a whole indicate that the rejection should be maintained.
4. Claims 1, 5, 9, 11 and 14 remain rejected under 35 U.S.C. 103 as being unpatentable over Capsoni et al. (PloS ONE Volume 7, Issue 5: e37555, pages 1-16; May 2012) in view of Desai et al. (US 2007/0282247; published Dec. 6 2007) and Keeney et al. (J Mater Chem B Mater Biol Med 3(45): 8757-8770; 2015).
The basis for this rejection is set forth at pages 17-20 of the previous Office Action (03 November 2025).
APPLICANT’S ARGUMENTS: Applicant reiterates the remarks previously made for currently amended claims 1, 9, 11, and 12 over the combination of Capsoni and Desai. Applicant argues that to cure the missing teachings of Capsoni and Desai, the Examiner cites Keeney. Applicant argues that there is no teaching nor suggestion from the combination of Capsoni, Desai, and Keeney, that provides the requisite motivation to a person of skill in the art to arrive at the claimed methods for treating neuropathy and pain comprising administering to a subject in need thereof a composition comprising a therapeutically effective amount of an NGF mutant that does not elicit pain, wherein the composition comprises micro-rods or nano-rods that deliver the NGF mutant, and they would have no expectation of success.
Applicant argues that Keeney allegedly discloses LbL techniques for drug delivery. Applicant notes that Keeney is wholly silent regarding NGF mutants, let alone those NGF mutants that do not elicit pain for the treatment of subjects in need thereof, much less methods for treating neuropathy and pain comprising administering to a subject in need thereof a composition comprising a therapeutically effective amount of an NGF mutant that does not elicit pain, wherein the composition comprises micro-rods or nano-rods that deliver the NGF mutant, as required by currently pending claims 1, 5, 9, 11, and 14.
Applicant’s arguments have been fully considered but are not found persuasive for the reasons discussed above regarding claims 1, 2, 6-10, 15, 19, and 20 and for reasons of record. The scientific reasoning and evidence as a whole indicate that the rejection should be maintained.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/R.M.D/Examiner, Art Unit 1647 3/18/2026
/BRIDGET E BUNNER/Primary Examiner, Art Unit 1647