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 .
DETAILED ACTION
Amendments
In the reply filed 05/08/2026, Applicant has amended claims 8 and 22.
Claim Status
Claims 1-2, 8-9, 12, 15, 17, 21-24, 26 and 29 are pending.
Claims 24 and 26 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to non-elected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 04/15/2025.
Claims 1-2, 8-9, 12, 15, 17, 21-23 and 29 are considered on the merits.
Withdrawn Claim Objections
The prior objection to claims 8 and 22 because of typographical error is withdrawn in light of Applicant’s amendment to the claims.
Maintained 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 1-2, 8-9, 12, 15, 17, 21-22 and 29 stand rejected under 35 U.S.C. 103 as being unpatentable over Mousa et al., (Chem. Mater. 2022, 34, 2752-2763. IDS 05/05/2025) in view of Yu et al., (Acta Biomaterialia. 2022; 139: 4-21, of record), Álvarez et al., (Science. 2021; 374: 848-856 and supplemental p. 1-3. Cited in IDS 05/05/2025), and Ahmed et al., (Adv. Sustainable Syst. 2022, 6, 2100316, p. 1-8, of record).
With respect to claim 1, Mousa teaches generation of a copolymer P(EDOT-S/EDOT-OH) (named “A5”) and teaches injecting A5 copolymer into the agarose gel cast with a physiological buffer generates a stable and highly conductive hydrogel (e.g., abstract). Thus, Mousa teaches a composition comprising (a) a copolymer comprising (i) a sulfonatoalkoxy EDOT monomer (i.e., EDOT-S) and (ii) an EDOT monomer functionalized with a hydroxyl group (i.e., EDOT-OH), and (b) a hydrogel material (i.e., an agarose gel). Mousa teaches this water-processable, syringe-injectable, and self-doped PEDOT-S polymer capable of forming a conductive hydrogel in tissue mimics is suitable for future applications within in vivo electronics, in treating Parkinson’s disease, epilepsy, vagus nerve stimulation, and pain (abstract and p. 2752, left col).
However, Mousa is silent on a plurality of bioactive peptide amphiphiles in claim 1 (b), nor teach the sequences in claims 15, 17 and 21-22.
Yu summarizes the use of injectable conducting polymer-based hydrogels for tissue engineering and for promoting the repair of damaged tissues such as neurological treatment (e.g., abstract). Yu teaches that hydrogels can be intrathecally implanted into localized impaired areas to efficaciously treat CNS diseases, including spinal cord injury (SCI), and soft matrix cues and electrical signal transmission in hydrogels have been demonstrated to be two key factors for improving the survival, differentiation, and functional expression of neural progenitor cells (NPCs) (e.g., p. 15, para. 4.1 “Neurological treatment”).
Álvarez teaches a plurality of bioactive peptide amphiphile (PA) that promotes recovery from spinal cord injury (e.g., abstract, related to claim 1 (b)). Alvarez teaches the IKVAV-PA2 comprises a sequence of C16AAGGEEEEGIKVAV (supplemental p. 2, para 1), which comprises a hydrophobic tail comprising a 8-24 carbon alkyl chain (i.e., C16), the structure peptide segment having a total propensity for forming β-sheet conformations of 4 or less comprising A2G2 (SEQ ID NO: 2) (i.e., AAGG), the charged peptide segment comprising EEEE (SEQ ID NO: 3) (see EEEE in the above sequence), the bioactive moiety comprising IKVAV (SEQ ID NO: 1) (see IKVAV in the above sequence), and the bioactive moiety is attached to the charged peptide segment by a linker that is a single glycine residue (see a single G between the bioactive moiety IKVAV and the charged peptide segment EEEE in the above sequence). The sequence of IKVAV-PA2 (C16AAGGEEEEGIKVAV) is 100% identical to the claimed sequence of SEQ ID NO: 11 (C8-24-A2G2E4GIKVAV). Thus, Alvarez teaches claims 15, 17 and 21-22. Álvarez teaches the bioactive PA mimics the natural ECM fibrils and incorporates bioactive signals to promote vascular growth, axonal regeneration, myelination, survival of motor neurons, reduced gliosis, and functional recovery in a model of spinal cord injury (abstract and p. 1, left col and middle col).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the composition comprising an EDOT-S/EDOT-OH copolymer and a hydrogel material suggested by Mousa, by combining a plurality of bioactive peptide amphiphiles with claimed sequence taught by Álvarez and using the composition in the repair of spinal cord injury as suggested by Yu with a reasonable expectation of success. Since Mousa teaches this water-processable, syringe-injectable, and self-doped copolymer forms a conductive hydrogel that is suitable for use in treating Parkinson’s disease, epilepsy, vagus nerve stimulation, and pain (abstract and p. 2752, left col), since Yu suggests the use of injectable conducting polymer-based hydrogels for promoting the repair of damaged tissues such as spinal cord injury (e.g., abstract and p. 15, para. 4.1), and since Álvarez teaches the bioactive PA mimics the natural ECM fibrils and incorporates bioactive signals to promote functional recovery in a model of spinal cord injury (abstract and p. 1, left col and middle col), one of ordinary skill in the art would have had a reason to combine a plurality of bioactive peptide amphiphiles of Álvarez in the injectable conductive hydrogel of Mousa in order to use the composition to promote functional recovery in damaged tissue such as spinal cord injury (see Yu, p. 15, para. 4.1 and Álvarez, p. 1, middle col, last para).
In regard to i) the copolymer being retained within the hydrogel material, Mousa teaches injecting A5 copolymer into the agarose gel cast with a physiological buffer generates a stable hydrogel (e.g., abstract and Fig 1b-1d for “limited diffusion” after 2 hours or 15 days), thus teaches the copolymer is retained within the hydrogel material.
In regard to i) hydrogen bonding between the copolymer and the hydrogel material, Mousa teaches that in the copolymer, there are =O atoms (i.e., hydrogen acceptors) and -OH (i.e., either hydrogen donor or acceptor) in both EDOT-S and EDOT-OH (see Mousa Scheme 2 in p. 2758). Mousa teaches the hydrogel material being agarose (e.g., abstract), which comprises -OH groups (i.e., either hydrogen donors or acceptors). Accordingly, one of ordinary skill in the art would have immediately understood that there would be hydrogen bonding between hydrogen donors (-OH groups) in the copolymer and hydrogen acceptors (-OH groups) in the agarose, or between hydrogen acceptors (-OH or =O groups) in the copolymer and hydrogen donors (-OH groups) in the agarose. Furthermore, since Mousa teaches the copolymer is retained within the agarose (see above), one of ordinary skill in the art would have appreciated that the hydrogen bonding between the copolymer and the agarose would contribute to the retention of the copolymer within the hydrogel material.
In regard to ii) the copolymer forming particles having an average diameter of at least 2000 nm, it is noted that this limitation is directed to the natural property of the claimed copolymer. MPEP 2112.01(II) recites that "products of identical chemical composition cannot have mutually exclusive properties. A chemical composition and its properties are inseparable." Since Mousa teaches a copolymer that is identical to that in claim 1 (a) (see above), the property of Mousa’s copolymer would be the same as claimed, i.e., forming particles having an average diameter of at least 2000 nm.
Nevertheless, Mousa teaches A5 (the EDOT-S/EDOT-OH copolymer) has a large polymer dispersion index (Mw being 174,000 Da) indicating that A5 forms aggregates in solution (p. 2757, last para – p. 2758, para 1. It is noted that these aggregates are equivalent to the claimed particles formed by the copolymer). To analyze the nanoparticles of the A5, Mousa teaches the Dynamic Light Scattering measurement (Supporting Information, p. 12) that “A5 was dissolved in prefiltered 1 mM NaCl solution and ultrasonicated. The solution was then filtered (0.2 μm PVDF) before analysis.” Thus, Mousa teaches the aggregates formed by A5 have a diameter of at least 0.2 μm evidenced by the necessity of ultrasonication (to break down the aggregates/particles) and filtration through a 0.2 μm filter. Furthermore, prior art Ahmed aims to produce thick films of PEDOT:PSS conducting polymers (e.g., abstract) and teaches PEDOT colloidal particles undergo a fast flocculation leading to an increase of particle size by about 100 times, the flocculation leads to particles of the order of 100 microns in size (p. 2, end of left col. – right col. See Fig 1C the particles being about 500 microns). Thus, Ahmed indicates that the starting PEDOT colloidal particles before the flocculation have a size in the order of several microns (i.e., the order of 100 microns after flocculation / about 100 times increase).
Accordingly, one of ordinary skill in the art would have immediately expected that the EDOT-S/EDOT-OH copolymer of Mousa would form aggregates/particles having an average diameter of at least 2000 nm (i.e., 2 microns) since Ahmed indicates that the PEDOT colloidal particles have a size in the order of several microns (see above).
In regard to iii) leakage of the copolymer from the hydrogel being less than 10% over the course of 7 days in claim 1 and less than 5% in claim 12, as stated supra, Mousa teaches the EDOT-S/EDOT-OH copolymer (“A5”) can be injected into an agarose gel cast with a physiological buffer to generate a stable hydrogel (see e.g., abstract). Mousa also teaches in a diffusion assay that A5 in agarose gel prepared with Ringer buffer has “limited diffusion” after 15 days (p. 2755, left col, last para – right col, para 1, see Fig 1d the 4th bar showing the A5 diffusion being non-detectable, and see p. 2753, right col, para 3 “Characterization of PEDOT-S Diffusion” for method of assay). Thus, Mousa suggests that leakage of the copolymer from the hydrogel is likely to be less than 10%, or less than 5%, over the course of 7 days. Accordingly, one of ordinary skill in the art would have appreciated that Mousa’s composition comprising an EDOT-S/EDOT-OH copolymer and a hydrogel material (A5 in an agarose gel cast with a physiological buffer) would have had leakage of the copolymer from the hydrogel be less than 10% or less than 5% over the course of 7 days as suggested by Mousa.
In regard to iv) the copolymer enhancing bioactivity of the bioactive PA in the hydrogel material compared to the bioactivity of PA not contained in the hydrogel material in claim 1 and the enhanced bioactivity comprising enhanced neural maturation in claim 29, it is noted that this limitation is directed to the property of the claimed composition such that the composition, comprising the copolymer in the hydrogel material and the bioactive PA, has enhanced bioactivity compared to the PA alone. Since Mousa, in view of Yu and Álvarez, suggests a composition that is identical to that in claim 1 (see above), the property of the composition in prior art would be the same as claimed, i.e., having enhanced bioactivity, e.g., enhanced neural maturation, compared to the PA alone. See MPEP 2112.01(II).
Nevertheless, as stated supra, Yu teaches injectable conducting polymer-based hydrogels can efficaciously treat CNS diseases, including spinal cord injury (SCI), because soft matrix cues and electrical signal transmission in hydrogels have been demonstrated to be two key factors for improving the survival, differentiation, and functional expression of neural progenitor cells (NPCs) (e.g., p. 15, para. 4.1 “Neurological treatment”, related to enhanced neural maturation in claim 29).
Accordingly, one of ordinary skill in the art would have immediately expected that the copolymer in the hydrogel material of Mousa (i.e., an injectable conducting polymer-based hydrogel providing soft matrix cues and electrical signal transmission) would improve the survival, differentiation, and functional expression of neural progenitor cells (i.e., enhance neural maturation) to efficaciously treat CNS diseases including spinal cord injury as indicated by Yu. Since Álvarez teaches the bioactive PA is used to promote functional recovery in spinal cord injury (see above), one of ordinary skill in the art would have expected that the copolymer in the hydrogel material of Mousa would enhance the bioactivity of the bioactive PA of Álvarez, e.g., enhance neural maturation, in treating spinal cord injury, as compared to the PA alone.
With respect to claim 2 directed to the sulfonatoalkoxy EDOT monomer comprising EDOT-S, as stated supra, Mousa teaches a copolymer P(EDOT-S/EDOT-OH) (named “A5”, see e.g., abstract), comprising an EDOT-S monomer.
With respect to claim 8 directed to the sulfonatoalkoxy EDOT monomer and the EDOT-OH monomer at a ratio of 1:10 to 10:1, Mousa teaches the ratio of EDOT-S/EDOT-OH in A5 being 85/15 (i.e., about 6:1) (see Table 1 in p. 2756).
With respect to claim 9 directed to the sulfonatoalkoxy EDOT monomer and the EDOT-OH monomer at a ratio of 4:1, Mousa teaches the ratio of EDOT-S/EDOT-OH being 85/15 in A5 (i.e., about 6:1), and 75/25 (i.e., about 3:1) in A5 synthesized with addition of 10% EDOT-OH (see Table 1, row 1 and row 3, in p. 2756). Mousa also teaches an A5 synthesized with addition of 5% EDOT-OH (see Fig 3b-3f), which would be expected to have a ratio of EDOT-S/EDOT-OH being between 6:1 and 3:1.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the composition of Mousa in view of Yu, Álvarez and Ahmed, by adjusting the addition of EDOT-OH as suggested by Mousa to arrive at the claimed ratio of EDOT-S/EDOT-OH being 4:1 with a reasonable expectation of success. Since Mousa aims to generate copolymers of EDOT-S/EDOT-OH with different ratios of the monomers to evaluate the dispersion and conductivity of the copolymers (see e.g., p. 2761, right col, last three sentences), one of ordinary skill in the art would have had a reason to adjust the additional amount of EDOT-OH to EDOT-S in order to optimize the copolymers for applications. Notably, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. It is a routine procedure to optimize component amounts to arrive at an optimal product that is superior for its intended use. See M.P.E.P. §2144.05.
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Response to Traversal:
Applicant’s arguments filed on 05/08/2026 are acknowledged.
Applicant argues that Alvarez teaches the cross-linking of bioactive PA by 5 mM CaCl2 decreases supramolecular motion and reduces bioactivity of the PA, and Mousa teaches a cross-linked hydrogel, thus the skilled artisan would anticipate that incorporating a bioactive PA into the hydrogel of Mousa, would therefore decrease the bioactivity of the peptide amphiphile (Remarks, p. 6-8).
Applicant’s arguments have been fully considered but they are not persuasive. The detailed responses are listed as follows.
In response to Applicant’s argument that Alvarez discloses experiments wherein bioactive PAs were cross-linked with 5 mM CaCl2, which is clearly a higher concentration than that of the DMEM/F12 medium cited by the Examiner, and Alvarez further discloses that this cross-linking decreases supramolecular motion and reduces bioactivity of the PA (Remarks, p. 7, para 2), Applicant indeed correctly points out the fact that the 5 mM CaCl2 used to cross-link PAs is clearly a higher concentration than that of CaCl2 used in the DMEM/F12 medium for culturing the hNPCs and testing the bioactivity of PAs. To reiterate Applicant’s findings and Examiner’s response, Alvarez tests the bioactivities of uncross-linked and cross-linked PAs in hNPCs cultured in DMEM/F12 medium (see Fig 2C for DMEM/F12 medium for hNPC culture and Fig 2J for results in hNPCs treated with PAs in the absence or presence of extra Ca2+, also see p. 3, left column for teaching of PA mixed with 5 mM CaCl2 “which is known to electrostatically cross-link negatively charged PA fibers”). The DMEM/F12 medium comprises 1 mM CaCl2. Thus, Alvarez discloses that uncross-linked PA is bioactive in a physiological medium containing 1 mM CaCl2, however, when PA is mixed with non-physiological higher molarity of CaCl2 (e.g., 5 mM CaCl2) and is cross-linked, the cross-linked PA has decreased supramolecular motion and reduced bioactivity.
In response to Applicant’s argument that it is clear that the skilled artisan reading the disclosure of Alvarez would be expressly discouraged from using a crosslinked hydrogel containing bioactive PAs, as this cross-linking is demonstrated to be detrimental to bioactivity, and Mousa indeed teaches such a cross-linked hydrogel (Remarks, p. 7, para 2), Applicant seems to argue that “this cross-linking” of PA of Alvarez is equivalent to “a cross-linked hydrogel” of Mousa. As discussed above, Alvarez discloses that the cross-linked PA (e.g., by 5 mM CaCl2) has decreased supramolecular motion and reduced bioactivity. Thus, one of ordinary skill in the art would have been discouraged from using 5 mM CaCl2 to avoid cross-linking PA.
However, Mousa teaches a cross-linked hydrogel, i.e., a 0.5% agarose gel in Ringer buffer (see e.g., p. 2753, right col, para 3 “Characterization of PEDOT-S Diffusion”) and teaches Ringer buffer “is a water solution of physiological salt concentrations mimicking body fluids” (p. 2755, left col, last para). The Ringer buffer contains 1.4-2.2 mM CaCl2 depending on modifications. It is noted that most of classic media, such as DMEM, contain 1.8 mM CaCl2. Thus, Mousa’s cross-linked hydrogel has a quarter to less than a half of the concentration of CaCl2 needed to cross-link PAs.
Furthermore, one of ordinary skill in the art would have understood that Mousa’s 0.5% agarose gel would have a pore size in the magnitude of micrometers, and since Alvarez teaches the PA molecules have a β sheet spacing in a range of angstroms and the motion of the PAs (the root mean square fluctuation (RMSF), which is a measure of the average displacement of a PA molecule during the last 5 µs of the simulation) around 4-6 nanometers (see Figure 1C and 1E), one of ordinary skill in the art would have immediately expected that the motion of PAs of Alvarez would not have been suppressed by Mousa’s cross-linked hydrogel.
Therefore, one of ordinary skill in the art would have expected that Alvarez’s PA would not have been cross-linked in Mousa’s hydrogel, and further, the motion of PAs would not have been suppressed by Mousa’s cross-linked hydrogel, thus, the PA of Alvarez would have been active in the cross-linked hydrogel of Mousa.
In response to Applicant’s argument that The Examiner's statement that Mousa teaches the conductive hydrogel is "cast with a physiological buffer Ringer buffer" is misleading. Rather, Mousa teaches that diffusion of the copolymer A5 was tested in "Ringer cast agarose", which the skilled artisan would recognize as a physically crosslinked gel. As such, the skilled artisan would anticipate that incorporating a bioactive PA into such a crosslinked gel would reduce the bioactivity of the PA per the teachings of Alvarez (Remarks, p. 7, last para.), as stated supra, Examiner indeed means to refer Mousa’s Ringer cast agarose gel as a physically crosslinked gel prepared in a physiological buffer (i.e., Ringer buffer) comprising physiological salt concentrations and a pore size in the magnitude of micrometers. As discussed above, one of ordinary skill in the art would have expected that Alvarez’s PA would not have been cross-linked in Mousa’s physically crosslinked hydrogel, and further, the motion of PAs would not have been suppressed by Mousa’s physically crosslinked hydrogel, thus, Alvarez’s PA would have been active in the physically crosslinked hydrogel of Mousa.
In response to Applicant’s argument that the diffusion characteristics of A5 are only shown in such a ringer-agarose gel over the course of 2 hours, and as such this ringer-cast agarose hydrogel does not meet the limitations of claim 1 with regard to the recited leakage of the copolymer from the hydrogel (Remarks, p. 7, last para.), on the contrary, the prior Office action (mailed on 02/09/2026, see page 9) quotes:
“Mousa also teaches in a diffusion assay that A5 in agarose gel prepared with Ringer buffer has “limited diffusion” after 15 days (p. 2755, left col, last para – right col, para 1, see Fig 1d the 4th bar showing the A5 diffusion being non-detectable, and see p. 2753, right col, para 3 “Characterization of PEDOT-S Diffusion” for method of assay). Thus, Mousa suggests that leakage of the copolymer from the hydrogel is likely to be less than 10%, or less than 5%, over the course of 7 days. Accordingly, one of ordinary skill in the art would have appreciated that Mousa’s composition comprising an EDOT-S/EDOT-OH copolymer and a hydrogel material (A5 in an agarose gel cast with a physiological buffer) would have had leakage of the copolymer from the hydrogel be less than 10% or less than 5% over the course of 7 days as suggested by Mousa.”
To reiterate the timing, Mousa’s teaching (p. 2753, right col, para 3) is quoted below (bolded and underlined by examiner):
“Characterization of PEDOT-S Diffusion. PEDOT-S (10 mg/mL, 4 μL) and polyornithine-CY3 (10 mg/mL, 4 μL) were injected using a 10 μL Hamilton syringe into an agarose gel (0.5% in Ringer buffer or Milli-Q water) in 6-well microtiter plates with a 15 mm separation (spot size 2 mm). After 2 h, the size of the spot was measured again. After 15 days, the diffusion ratio was measured as the distance between the PEDOT-S injection spot and the polyornithine-PEDOT precipitation divided by the total distance between the PEDOT-S and polyornithine-CY3 injections”.
Thus, Mousa clearly demonstrates that the copolymer A5 in a ringer-agarose gel has “limited diffusion” after 15 days (see Fig 1d the 4th bar showing the A5 diffusion being non-detectable), and this teaching meets the limitations of claim 1 with regard to the recited leakage of the copolymer from the hydrogel.
In response to Applicant’s argument that Mousa’s stable hydrogel was formed by extruding the copolymer wire into 0.01 M CaCl2, equivalent to 10 mM CaCl2. See Experimental section and page 14 of the supplementary information, "Long Term A5 water stability". This concentration CaCl2 used in forming the stable hydrogel of Mousa is clearly higher than the concentration of CaCl2 used in Alvarez to cross-link the PA (Remarks, p. 7-8), Applicant is reminded the cited teaching of Mousa is referred to in testing the copolymer A5 stability in pure water (i.e., the cross-linked A5 copolymer remains stable and maintains initial conductivities for 7 months in pure water), but is not related to A5 injected into a 0.5% agarose gel prepared in Ringer buffer (see discussion above with respect to testing diffusion of the copolymer A5 in a ringer-agarose gel). Thus, the using 10 mM CaCl2 in the cited teaching does not negate the teaching for testing diffusion of the copolymer A5 in a Ringer-agarose gel, as discussed above.
In response to Applicant’s argument that the Examiner is relying on impermissible hindsight reconstruction based upon the data presented in the instant application itself in formulating the present obviousness rejections (Remarks, p. 8, end of para 1), it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In the instant case, Mousa teaches a composition comprising (a) a copolymer of EDOT-S/-OH, and (b) a hydrogel material (i.e., a 0.5% agarose gel prepared in Ringer buffer). The only difference between Mousa and the instant invention is that Mousa is silent on a plurality of bioactive peptide amphiphiles. Yu and Alvarez are cited to make obvious combining bioactive PAs in the hydrogel of Mousa in order to use the composition to promote functional recovery in damaged tissue such as spinal cord injury with a reasonable expectation of success. Thus, the examination does not include knowledge gleaned only from the applicant's disclosure.
In response to Applicant’s argument of surprising and unexpected results that the copolymer PEDOT-S/OH improved bioactivity compared to that of the bioactive peptide amphiphile alone, and there is synergistic effect between PEDOT-S/OH (referred to as "PS2") and the bioactive PA (See page 50 line 17 to page 54 line 7, and Figures 6-11) and hydrogen bonding occurs in the PA + PS2 (Remarks, p. 9-10), as a first matter, the asserted surprising and unexpected results are obtained from one single composition - PEDOT-S/OH (at a ratio of 4:1) combined with the bioactive PA with the sequence in claim 22 (PA + PS2), which are not commensurate in scope with the claimed invention in claim 1 encompassing a genus of compositions comprising (a) a copolymer comprising (i) at least one EDOT-S monomer or at least one any cationic EDOT monomer, and (ii) at least one EDOT-OH, at any ratio, and (b) any hydrogel comprising a plurality of any type of bioactive PA. Additionally, the asserted synergistic effect between PEDOT-S/OH and the bioactive PA (containing A2G2 structure peptide segment) (see specification, p. 51, lines 20-26 and Figure 8) is not commensurate in scope with the claimed peptide amphiphiles that contain any structure peptide segment, including the V2A2 structural peptide segment that does not have the asserted synergistic effect disclosed by specification.
Furthermore, as stated supra, prior art Yu teaches injectable conducting polymer-based hydrogels can efficaciously treat CNS diseases, including spinal cord injury (SCI), because soft matrix cues and electrical signal transmission in hydrogels have been demonstrated to be two key factors for improving the survival, differentiation, and functional expression of neural progenitor cells (NPCs) (e.g., p. 15, para. 4.1 “Neurological treatment”). Accordingly, one of ordinary skill in the art would have expected that the copolymer in the hydrogel material of Mousa (i.e., an injectable conducting polymer-based hydrogel providing soft matrix cues and electrical signal transmission) would improve the survival, differentiation, and functional expression of neural progenitor cells (i.e., enhance neural maturation) to efficaciously treat CNS diseases including spinal cord injury as indicated by Yu. Since Álvarez teaches the bioactive PA is used to promote functional recovery in spinal cord injury (see above), one of ordinary skill in the art would have expected that the copolymer in the hydrogel material of Mousa would enhance the bioactivity of the bioactive PA of Álvarez, e.g., enhance neural maturation, in treating spinal cord injury, as compared to the PA alone.
Finally, MPEP § 2145 states that a showing of unexpected results must be based on evidence, not argument or speculation. In re Mayne, 104 F.3d 1339, 1343-44, 41 USPQ2d 1451, 1455-56 (Fed. Cir. 1997) (conclusory statements that claimed compound possesses unusually low immune response or unexpected biological activity that is unsupported by comparative data held insufficient to overcome prima facie case of obviousness). In the instant case, regarding the asserted synergistic effect between PEDOT-S/OH and the bioactive PA, Applicant merely discloses comparison between bioactive PA alone and PA + PEDOT-S/OH (see Fig 8), but does not provide a necessary control of PEDOT-S/OH alone, thus the asserted “synergistic” effect is not supported by side-by-side comparative data.
Claim 23 stands rejected under 35 U.S.C. 103 as being unpatentable over Mousa et al., (Chem. Mater. 2022, 34, 2752-2763. IDS 05/05/2025) in view of Yu et al., (Acta Biomaterialia. 2022; 139: 4-21, of record), Álvarez et al., (Science. 2021; 374: 848-856 and supplemental p. 1-3. Cited in IDS 05/05/2025), and Ahmed et al., (Adv. Sustainable Syst. 2022, 6, 2100316, p. 1-8, of record), as applied to claim 1 above, and further in view of Stupp et al., (US 2012/0294902, prior art of record).
Claim 23 is directed to the hydrogel material further comprising a filler PA which does not comprise a bioactive moiety.
However, Mousa, Yu, Álvarez and Ahmed are silent on a filler PA that does not comprise a bioactive moiety in claim 23.
Stupp teaches a peptide amphiphile (PA) and method of electrostatically control bioactivity of the IKVAV peptide epitope (see e.g., abstract). Stupp teaches a composition comprising (a) a first PA comprising (1) a hydrophobic segment, (2) a β-sheet-forming structural peptide segment; (3) a charged peptide segment, and (4) a signaling epitope (i.e., a bioactive moiety); and (b) a second peptide amphiphile comprising the peptide sequence (V)x(A)y(E)z-NH, wherein x=y=z=2 (see e.g. [0021] and reference claim 10). It is noted that this second peptide amphiphile also comprises a hydrophobic segment in addition to the peptide sequence to make it a peptide amphiphile. Thus, Stupp teaches a composition comprising, in addition to the first PA having a bioactive moiety, a second PA (i.e., a filler PA) comprising a hydrophobic segment comprising an acyl group of six or more carbons (i.e., a hydrophobic non-peptide tail), a peptide sequence of V2A2 (i.e., a structural peptide segment, see e.g., [0055]), a peptide sequence of E2 (i.e., a charged peptide segment, see e.g., [0056]), without a bioactive moiety, thus teaches claim 23.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the composition comprising a copolymer and a hydrogel material comprising a plurality of bioactive peptide amphiphiles as suggested by Mousa in view of Yu, Álvarez and Ahmed, by combining a second filler PA without a bioactive moiety as taught by Stupp with a reasonable expectation of success. Since Álvarez teaches it would be advantageous to have easy tunability of signal density (Álvarez, p. 1, middle col, para 1), and since Stupp teaches a composition comprising a first bioactive PA and a second filler PA without a bioactive moiety (see e.g. [0021] and reference claim 10), one of ordinary skill in the art would have had a reason to combine a second filler PA without a bioactive moiety as taught by Stupp into the hydrogel material comprising a bioactive PA in order to tune the signal density of the bioactive moiety by adjusting the ratio of the bioactive PA versus the filler PA without a bioactive moiety.
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Response to Traversal:
Applicant’s arguments filed on 05/08/2026 are acknowledged and have been discussed above.
Conclusion
THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 extension fee 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 date of this final action.
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jianjian Zhu whose telephone number is (571)272-0956. The examiner can normally be reached M - F 8:30AM - 4PM (EST).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Douglas (Doug) Schultz can be reached on (571) 272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JIANJIAN ZHU/Examiner, Art Unit 1631
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
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