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
Claims 1, 4, 12, 32, 45, 54, 56, 57, 66, 68, 71, 77, 84, and 92-98 are pending. Claims 92-98 are newly added; claims 2, 8, 16, 22, 28, 36, and 42, were canceled; and claims 1, 4, 12, 32, 45, 57, and 68 were amended in the Reply filed 12/24/2025. Claims 45, 66, 77, 84, 94-95, or 97-98 are withdrawn. Claims 1, 4, 12, 32, 54, 56-57, 68, 71, 92-93, and 96 are presently considered.
Election/Restrictions
Applicant's election with traverse of Group I (original claims 1-2, 4, 8, 12, 16, 22, 28, 32, 36, 42, 45, 54, 56, 57, 66, 68, and 71) and the species without traverse of Example 2 (p. 24-25) and Figure 1, namely a composition comprising (MOA)1155K55 at 5 wt%, (MOA)155E55 at 5 wt%, (MOA)200L30 at 6 wt%, and water in the reply filed on 7/25/2025 was previously acknowledged. The traversal was found not persuasive for reasons of record (see Action mailed 9/25/2025 at 2-3), and the requirement was deemed proper and made Final.
The originally elected species is understood to read upon amended claim 1 wherein (MOA)155K55 is Substructure I having an m of 155 and a p of 55; (MOA)155E55 is Substructure II having an n of 155 and a q of 55; and (MOA)200L30 is Substructure III having an r of 155 and a t of 55. The elected species is understood to read upon amended claims 1, 4, 12, 32, 54, 56-57, 68, 71, 92-93, and 96. However, the elected species does not read upon amended claim 45, which now recites static values rather than ranges, and the static values shown are not present in the originally elected species. The elected species does not read upon claims 94-95 as n and m are 155 in the elected species. The elected species does not read upon claims 97-98 as p and q are 55 in the elected species. Claims 66, 77, and 84 remain withdrawn for reasons of record. Accordingly, the originally elected species does not read upon instant claim 45, 66, 77, 84, 94-95, or 97-98.
Following extensive search and examination, the originally elected species has again been deemed anticipated and/or obvious in view of the prior art as applied below. Per MPEP § 803.02(III)(A), claims directed to non-elected species are withdrawn.
Claims 77 and 84 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 7/25/2025.
Claims 45, 66, 94-95, and 97-98 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 7/25/2025.
Claims 1, 4, 12, 32, 54, 56-57, 68, 71, 92-93, and 96 are presently considered.
Priority
The priority claim to Provisional US Application 62/824,571 as filed 3/27/2019 is acknowledged. However, Examiner notes that the instant Specification as filed 9/27/2021 appears to differ substantially from the provisional at pages 6-14 of the instant Specification.
Information Disclosure Statement
The IDS filed 12/24/2025 is acknowledged and presently considered.
Claim Interpretation
For purposes of examination, unless otherwise stated, the claim scope has been interpreted as set forth below per the guidance set forth at MPEP § 2111.
Amended claim 1 is representative of the pending claim scope. Applicable claim interpretations are provided below.
“Comprising” is an open-ended transitional term (see, e.g., MPEP § 2111.03(I)), wherein additional steps or components are not excluded. However, “‘[c]omprising’ is a term of art used in claim language which means that the named elements are essential” (see, e.g., id.; see also Genentech, Inc. v. Chiron Corp., 112 F.3d 495, 501, 42 USPQ2d 1608, 1613 (Fed. Cir. 1997)).
Substructures I, II, and III do not identify orientation (N to C or C to N), length of the total copolypeptide, nor limit additional structures that may be present in the copolypeptide (e.g., small molecules, PEG moieties, branching, etc.). Furthermore, Substructure I, II, and III are reasonably understood to broadly encompass branched and dendritic polypeptides.
The term “MO” is understood to refer to L-methionine sulfoxide (see, e.g., Spec. filed 9/27/2021 at 2 at lines 15-20).
Additional claim interpretations are set forth below.
Claim Objections
Claim 1 is objected to because of the following informalities:
Amended claim 1 as filed 12/24/2025 contains a grammatical error at pages 3-4, namely at the amended phrase “each instance of Z is an amino acid residue independently selected from at least 85 mol % of the Z amino acid residues are…..”. It is assumed, that this should read “each instance of Z is an independently selected amino acid residue, wherein at least 85 mol %....”
Appropriate correction is required.
Withdrawn Claim Rejections
The rejection of claims 1-2, 4, 8, 12, 16, 22, 28, 32, 36, 42, 45, 54, 56-57, 68, and 71 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn in view of the cancelation of claims 2, 8, 16, 22, 28, 36, and 42, and the amendments to 1, 4, 12, 32, 45, 57, and 68.
The rejection of claims 1-2, 4, 8, 12, 16, 22, 28, 32, 36, 42, 45, 54, 56-57, 66, 68, and 71 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn in view of the cancelation of claims 2, 8, 16, 22, 28, 36, and 42, and the amendments to 1, 4, 12, 32, 45, 57, and 68.
Maintained or Revised Claim Rejections Necessitated by Amendment
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 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, 4, 12, 32, 54, 56-57, 68, 71, 92-93, and 96 are rejected under 35 U.S.C. 103 as being unpatentable over Deming et al.2 in view of Wollenberg et al.3.
Claim Interpretation: The applicable claim interpretation has been set forth in a separate section above, which is incorporated herein. Additional claim interpretations are set forth below.
Deming pertains to diblock copolypeptide hydrogels that form by the polyion complexation of a first and second copolypeptide (see, e.g., Deming at title, abs). Regarding instant claims 1, 4, 12, 32, 57, 92-93, substructure I of (MOA)4155K55, and substructure II of (MOA)155E55, Deming teaches and discloses polyion complexes (PIC) diblock copolypeptide hydrogel (DCHPIC) forming sequences (see, e.g., Deming at 15115 at col I-II at introduction, Fig. 1 on 15115, scheme 1 on 15116, Fig. 2 on 15117, Supp. at S2 at Table S1). Deming explicitly teaches and discloses (MOA)155Ex and (MOA)155Kx, wherein x is between 30-120 (see, e.g., Deming at Fig. 1 on 15114, 15115 at col II at final ¶, Fig. 2 at 15117, Supp. at S2 at Table S1) (see, e.g., MPEP § 2144.05(I), noting that in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists). Accordingly, compounds of form (MOA)155Ex and (MOA)155Kx are prior art elements, that would be predicted and expected to form hydrogels (see, e.g., Deming at title, abs, 15120 at col I). Regarding instant claim 1 and a concentration of “about 1% to about 15%”, Demining discloses and exemplifies compositions wherein compounds of form (MOA)155Ex and (MOA)155Kx are present at between 2 wt% and 15 wt% (see Deming at Fig. 2 on 15117) (see, e.g., MPEP § 2144.05(I), noting that in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists). Regarding instant claims 1, 4, 12, and substructures of I and II wherein X and Y’ are selected from methionine sulfoxide and alanine, Deming explicitly teaches and discloses (MOA)155Ex and (MOA)155Kx, wherein x is between 30-120 (see, e.g., Deming at Fig. 1 on 15114, 15115 at col II at final ¶, Fig. 2 at 15117, Supp. at S2 at Table S1), wherein MOA” is understood to refer to L-methionine sulfoxide-stat-L-alanine (see, e.g., Deming at 15115 at col II at final ¶, S3, S6, S8). Regarding instant claims 1, 4, 12, 32, and substructures I and II, wherein “at least 85 mol% of” X and Y’ are methionine sulfoxide, Deming explains that MOA” is understood to refer to L-methionine sulfoxide-stat-L-alanine (see, e.g., Deming at 15115 at col II at final ¶, S3, S6, S8), and that the alanine comprises “ca. 12 mol %” of the MOA polymer (see, e.g., Deming at 15115 at col II at § Results), and indicates that the Methionine sulfoxide comprises ~88 mol %(see, e.g., id.; see also id. at Scheme 1 on 15116, reproduced in part, below):
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Accordingly, the primary reference teaches the limitations pertaining to mol % of methionine sulfoxide present in both (MOA)155Ex and (MOA)155Kx (see, e.g., id.; see also Deming at S3, S6, S8). Regarding instant claim 1, and wherein each instance of C’ is lysine, Deming explicitly teaches and discloses (MOA)155Kx, wherein x is between 30-120 (see, e.g., Deming at Fig. 1 on 15114, 15115 at col II at final ¶, Fig. 2 at 15117, Supp. at S2 at Table S1), wherein such structure satisfies instant claim 22 because each instance of C’ is lysine. Regarding instant claim 1 and wherein each instance of A’ is glutamic acid, Deming explicitly teaches and discloses (MOA)155Ex, wherein x is between 30-120 (see, e.g., Deming at Fig. 1 on 15114, 15115 at col II at final ¶, Fig. 2 at 15117, Supp. at S2 at Table S1), wherein such structure satisfies instant claim 22 because each instance of A’ is glutamic acid. Regarding instant claim 54 and polydispersity of the first and second polypeptide of “less than 1.5”, Deming explicitly teaches and discloses compounds of form (MOA)155Ex and (MOA)155Kx, wherein x is between 30-120 (see, e.g., Deming at Fig. 1 on 15114, 15115 at col II at final ¶, Fig. 2 at 15117, Supp. at S2 at Table S1), and explicitly discloses that the dispersity of each polypeptide (Mw/Mn) is under 1.5 (see id. at S2 at Table S1). Regarding instant claim 56-57, and wherein the number of amino acids residues in the first polypeptide is ~90 to ~110% of the number in the second polypeptide, Deming explicitly teaches and discloses hydrogel compositions formed from stoichiometric (MOA)155E/Kx with different ionic segment lengths (i.e., x is 30, 60, 90, or 120) (see, e.g., Deming at Fig. 2 at 15117), including a 1:1 ratio of (MOA)155E60 and (MOA)155K60 (see id at Fig. 2(B), (C)). Such sequences are reasonably understood to be “about” (MOA)155E55 and (MOA)155K55. Regarding instant claim 71 and a composition comprising a salt or buffer, Deming explicitly teaches and discloses hydrogel compositions having a 1:1 ratio of (MOA)155E60 and (MOA)155K60, wherein the hydrogels form in the presence of a buffer (see, e.g., Deming at Fig. 2 at 15117; see esp. id. at Fig. 2(C)).
The primary reference differs from the instantly claimed invention as follows: Demining does not exemplify a combination of (MOA)155Ex and (MOA)155Kx, wherein a third copolypeptide comprising substructure III (“- Zr-D’t -”) is present at “about 1% to about 10%” as presently required by instant claim 1.
Wollenberg identifies that the diblock copolypeptide of (MOA)170Ln5 is a prior art element, wherein n is 12-39 (a.k.a., “DCHMO”) (see, e.g., Wollenberg at 532 at col II at § 3.1.2, 533 at Scheme 2, 534 at Table 2, 534 at Fig. 1(A)-(B), 536 at col I at 1st full ¶, S1 at § Chemical Abbreviations. Supp Figs. 5 and 10). Furthermore, the structure of (MOA)170L24 satisfies the structural requirements of instant claims 1, 32, 92-93, and 96 (compare id. with instant claims 1, 32, 92-93, and 96 regarding Z, D, r, t). Regarding instant claims 1 and concentrations, Wollenberg discloses that such sequences can be utilized at 2 wt% to 9 wt% (see, e.g., Wollenberg at Table 2 on 534, Fig. 5(b) on 537). (see, e.g., MPEP § 2144.05(I), noting that in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists). Regarding ranges of concentrations, Demining discloses and exemplifies compositions wherein compounds of form (MOA)155Ex and (MOA)155Kx are present at between 2 wt% and 15 wt% (see Deming at Fig. 2 on 15117); and Wollenberg discloses that (MOA)170L24 can be utilized at 2 wt% to 9 wt% (see, e.g., Wollenberg at Table 2 on 534, Fig. 5(b) on 537). Accordingly, claim 66 is directed to a composition falling within the ranges taught and suggested for use by the prior art (see, e.g., MPEP § 2144.05(I), noting that in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists). Regarding instant claim 68, 92-93, and molar ratios, it is noted that (MOA)155E60 and (MOA)155K60 would have a C’ to A’ ratio of 1:1 and an X to Y’ ratio of 1:1. Furthermore, (MOA)170L12-39 and (MOA)170L24 are understood to have a D’ to A’ ratio of approximately 24/60 or 0.4. In sum, compounds of substructures I, II, and III were prior art elements as taught by Deming and Wollenberg, which were taught and disclosed for use at the concentrations presently claimed.
Regarding the elected species, (MOA)170L12-39 and (MOA)170L24 are understood to be “about” (MOA)200L30, because (MOA)170Ln is a prior art element, wherein n is 12-39 (a.k.a., “DCHMO”) (see, e.g., Wollenberg at 532 at col II at § 3.1.2, 533 at Scheme 2, 534 at Table 2, 534 at Fig. 1(A)-(B), 536 at col I at 1st full ¶, S1 at § Chemical Abbreviations. Supp Figs. 5 and 10). Furthermore, 170 is “about” 200, and such prior art only differs from the elected species by the successive addition of the same chemical group (i.e., MOA)) (see, e.g., MPEP § 2144.09(II)).
Motivation to combine and predicted and expected results: A remaining question pertinent to a determination of obviousness may be simply stated as, “why would an artisan combine these sequences?” and “what would be the predicted and expected results?”. Deming explains that (MOA)155E60 and (MOA)155K60 form PIC hydrogels and are generally useful for the encapsulation of primary neural stem progenitor cells (NSPCs), and would generally be useful “as cell carriers” (see, e.g., Deming at 15119 at col II to 15120 at col I at bridging ¶). Similarly, Wollenberg identifies that (MOA)170Ln (a.k.a., “DCHMO”) can be utilized to encapsulate NSPCs (see, e.g., Wollenberg at Fig. 5), wherein “DCHMO may prove to be useful for ensuring robust survival and integration of transplanted NSPC within CNS injury microenvironments” (see, e.g., Wollenberg at 539 at col I at 1st partial ¶), and that “DCHMO is a suitable hydrogel carrier for neural stem cell transplantation applications and warrants further investigation as a therapeutic tool in CNS injury studies” (see, e.g., Wollenberg at 543 at col II at final ¶). Accordingly, an artisan would readily appreciate that (MOA)155E60, (MOA)155K60, and (MOA)170Ln (a.k.a., “DCHMO”) may each be utilized to form hydrogels useful as cell carriers, and in particular NSPCs. Therefore, an artisan would readily appreciate that, absent evidence to the contrary, such sequences in combination would continue to form hydrogels useful as a cell carrier, and in particular a carrier for NSPCs.
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s):The claimed invention is the combination of prior art polypeptides (e.g., (MOA)155E60, (MOA)155K60, and (MOA)170Ln), individually taught for use in the formation of hydrogels suitable for use in the encapsulation of primary neural stem progenitor cells (NSPCs) by the prior art; per MPEP § 2144.06(I), "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Accordingly, it would be obvious to combine the prior art sequences of (MOA)155E60, (MOA)155K60, and (MOA)170Ln) (or their obvious variants) in order to predictably and expectedly obtain a third composition that would predictably form a hydrogel suitable for use in the encapsulation of NSPCs, exactly as taught and suggested by the prior art.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to combine prior art elements, at known concentrations, in order to obtain results taught and disclosed by the prior art.
Accordingly, claims 1, 4, 12, 32, 54, 56-57, 68, 71, 92-93, and 96 are rejected.
Response to Arguments
Applicant's arguments filed 12/24/2025 have been fully considered but they are not persuasive. Arguments directed to withdrawn objections or rejections are moot. Remaining applicable arguments are addressed below.
Applicant addresses the maintained rejection under 35 USC 103 at pages 12-16 of the Reply (see, e.g., Reply filed 12/24/2025 at 12 final ¶to page 16 at 1st partial ¶). Applicant recites case law, which is undisputed but not applied to the merits or facts of the instant Application (see, e.g., Reply filed 12/24/2025 at 12-13 at bridging ¶), summarizes the rejection (see, e.g., Reply filed 12/24/2025 at 13 at 1st full ¶), and summarizes the general teachings of the prior art references (see, e.g., Reply filed 12/24/2025 at 13 at 3rd full ¶).
It is the Examiner’s understanding that Applicant mischaracterizes the claimed invention at page 13, because they assert that the claims are directed to compositions “that yield a physically crosslinked dual network (DN) of interpenetrating polyanionic complexes (PIC) and hydrophobically assembled domains (MO)”, but such language and limitations are not actually recited in the pending claim set. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Accordingly, arguments premised upon unclaimed features to distinguish the claimed invention over the prior art are not persuasive.
It is the Examiner’s understanding that Applicant is alleging that Deming and Wollenberg do not directly “teach or suggest physically mixing” the prior art compositions disclosed by Deming and Wollenberg (see, e.g., Reply filed 12/24/2025 at 13-14 at bridging ¶). In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, the claimed invention is the combination of prior art polypeptides (e.g., (MOA)155E60, (MOA)155K60, and (MOA)170Ln), individually taught for use in the formation of hydrogels suitable for use in the encapsulation of primary neural stem progenitor cells (NSPCs) by the prior art; per MPEP § 2144.06(I), "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Accordingly, it would be obvious to combine the prior art sequences of (MOA)155E60, (MOA)155K60, and (MOA)170Ln) (or their obvious variants) in order to predictably and expectedly obtain a third composition that would predictably form a hydrogel suitable for use in the encapsulation of NSPCs, exactly as taught and suggested by the prior art.
It is the Examiner’s understanding that Applicant is alleging that the art teaches away from combining the prior art elements, presumably on the assumption that an artisan would equate K180L20 with (MOA)170Ln, and conclude that mixing (MOA)155E/K60 with (MOA)170Ln would yield “a low-viscosity liquid” rather than a gel (see, e.g., Reply filed 12/24/2025 at 13-14 at bridging ¶). This is not persuasive for the following reasons: First, Applicant provides no basis for extrapolating data obtained with K180L20 to (MOA)170Ln, and the validity of this assumption does not appear credible in the absence of an unambiguous explanation. Second, although the Applicant alleges that Deming discloses
…a 5.0 wt.% PIC hydrogel ((M0A)155E/K60) mixed with K180L20 amphiphilic MO (chosen to match stiffness) failed to gel and produced only a liquid at 5.0 wt.%.
(see, e.g., Reply filed 12/24/2025 at 13-14 at bridging ¶, 16-17 at bridging ¶), Applicant fails to provide any citation for such a disclosure. Upon review, Applicant appears to have confused the image at Figure 4 and the disclosure at 15119 of Deming (see, e.g., Deming at Fig. 4 on 15118, 15119 at col I-II at bridging ¶), which discloses that 2.0% wt K180L20, in the absence of any (MOA)155E/K60, did not maintain a gel state after 3 days (see id). Accordingly, following review of Deming, Examiner is unaware, where exactly, Deming provides the alleged teaching relied upon by the Applicant. Accordingly, in the absence of such evidence, the basis for the alleged “teaching away” allegation appears non-existent. Third, Examiner notes that any suggestion of a “teaching away” is not persuasive because none of prior art references at issue “teach away” from the claimed invention since they do not actually “criticize, discredit, or otherwise discourage the solution claimed” (see, e.g., MPEP § 2141.02(VI)). Applicant has not identified any disclosure that “criticizes, discredits, or otherwise discourages the solution claimed”. Accordingly, no “teaching away” has been identified on record.
Allegations suggesting “lack of predictability” or “lack of reasonable expectation of success”: It is the Examiner’s understanding that Applicant is alleging a lack of predictability or otherwise a lack of reasonable expectation of success (see, e.g., Reply filed 12/24/2025 at 14 at 1st full ¶ to 15 at 3rd full ¶). This is not persuasive because the Applicant’s assertions do not reflect the proper legal standards for evaluating predictability. MPEP § 2143.02(II) explains that “[o]bviousness does not require absolute predictability”, but instead clarifies that only “at least some degree of predictability is required” (see, e.g., MPEP § 2143.02(II)). Here, the rejection explicitly addresses predictability and reasonable expectation of success, but Applicant fails to address the explicitly identified predicted and expected results set forth in the rejection. Here, the Examiner’s basis for “predictability” is merely based upon the presumption that the prior art is fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). As explained at MPEP § 2143.02, predictability and reasonable expectation of success are satisfied when “all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art”. Here zero evidence of unexpected results commensurate in scope with the requirements of MPEP 716.02 have been set forth on record, all elements of the claimed invention were known in the prior art, one of ordinary skill was fully enabled to combined each component using routine methods in the biochemical arts per the guidance of the primary reference, and the elements would have merely performed their art-recognized, respective functions (see Rejection, above). Accordingly, such arguments are not persuasive.
Applicant recites unclaimed limitations: It is the Examiner’s understanding that Applicant attempts to distinguish the claimed invention over the teachings of the prior art by referring to multiple unclaimed limitations (see, e.g., Reply filed 12/24/2025 at 14 at 1st full ¶ to 15 at 3rd full ¶, referring to storage modulus, viscoelastic behavior, gel-like behavior, delayed crossover, strain-induced softening, strain sweep data, self-healing, large-amplitude shear, gel integrity in physiologic media, etc., etc.; see esp. id. at 15 at 3rd full ¶, alleging that the prior art is “silent” regarding unclaimed limitations). In response, it is noted that the features upon which applicant relies are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Here, the parameters recited reflect a different rationale for combining the prior art elements than relied upon by the Examiner. Rather, here the predicted and expected results are set forth in the rejection, namely that because (MOA)155E60, (MOA)155K60, and (MOA)170Ln (a.k.a., “DCHMO”) may each be utilized to form hydrogels useful as cell carriers, and in particular NSPCs, that they could be combined to form a hydrogel useful as a cell carrier. This reflects MPEP § 2144.06(I), which states that "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
Applicant has a different rationale for arriving at the instant invention: It is the Examiner’s understanding that Applicant identifies that their rationale for arriving at the claimed invention differs from the rationale relied upon by the Examiner to establish obviousness (see, e.g., Reply filed 12/24/2025 at 14 at 1st full ¶ to 15 at 3rd full ¶, referring to storage modulus, viscoelastic behavior, gel-like behavior, delayed crossover, strain-induced softening, strain sweep data, self-healing, large-amplitude shear, gel integrity in physiologic media, etc., etc.).. Examiner notes that this is not persuasive because an examiner may support a determination of obviousness by relying upon a rationale that differs from the Applicant’s rationale (see, e.g., MPEP § 2144(IV)). Here, the Examiner’s rationales are explicitly identified in the rejection (i.e., MPEP § 2144.06(I)), but Applicant fails to address or specifically dispute these rationales supporting a determination of obviousness. Accordingly, it is neither disputed nor dispositive of obviousness that the Examiner did not support a rationale that was not actually relied upon to establish prima facie obviousness.
Allegations suggesting “inoperability” or lack of enabling disclosure regarding a prior art reference: It is the Examiner’s understanding that Applicant’s statements amount to a suggestion that the prior art is not fully enabled or operable for the combination of the prior art elements of (MOA)155E60, (MOA)155K60, and (MOA)170Ln (see, e.g., Reply filed 12/24/2025 at 14 at 1st full ¶ to 15 at 3rd full ¶, referring to storage modulus, viscoelastic behavior, gel-like behavior, delayed crossover, strain-induced softening, strain sweep data, self-healing, large-amplitude shear, gel integrity in physiologic media, etc., etc.). If Applicant is attempting to allege that the prior art is not enabling or inoperable Applicant is directed to MPEP § 2121(I), which notes that the prior art is presumed fully enabled for all that it discloses, and the burden is on the Applicant to rebut the presumption of operability (see, e.g., MPEP § 2121(I); MPEP § 716.07). No evidence of inoperability commensurate in scope with the requirements of MPEP § 716.07 have been placed on record at this time; critically, arguments of counsel cannot take the place of evidence in the record (see, e.g., In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965), and evidence is required to rebut the presumption of operability. The Examiner’s position is that the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)), including “all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments” (see, e.g., MPEP § 2123(I)). Accordingly, the Applicant has not satisfied their burden to rebut the presumption of operability of the prior art at this time (see, e.g., MPEP § 2121(I); MPEP § 716.07). Examiner notes that a showing under MPEP § 716.07 must distinguish the claimed invention over the prior art.
Allegations suggesting “skepticism of experts”: It is the Examiner’s understanding that Applicant’s statements amount to a suggestion that the Examiner’s position would be met with skepticism of experts (see, e.g., Reply filed 12/24/2025 at 14 at 1st full ¶ to 15 at 3rd full ¶, referring to storage modulus, viscoelastic behavior, gel-like behavior, delayed crossover, strain-induced softening, strain sweep data, self-healing, large-amplitude shear, gel integrity in physiologic media, etc., etc.). If Applicant means to suggest the existence of skepticism of experts, such evidence should be filed per MPEP § 716.05 as evidence is required to establish skepticism of experts. In the absence of such evidence, such statements are understood to be unsupported conjecture of counsel. The prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)), including “all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments” (see, e.g., MPEP § 2123(I)), and no objective evidence rebutting this presumption has been placed on record to date.
Arguments directed to efficacy of gel formation is not sufficient to rebut obviousness: It is the Examiner’s understanding that Applicant is suggesting that gel formation may or may not occur in some conditions (e.g., salt, pH, temperature, etc.) (see, e.g., Reply filed 12/24/2025 at 14 at 1st full ¶ to 15 at 3rd full ¶, referring to storage modulus, viscoelastic behavior, gel-like behavior, delayed crossover, strain-induced softening, strain sweep data, self-healing, large-amplitude shear, gel integrity in physiologic media, etc., etc.). This is understood to be an argument regarding efficacy of reliable gel formation under broad conditions. As explained at MPEP § 2143(I)-(II), “Conclusive proof of efficacy is not required to show a reasonable expectation of success”. Here, all that is required is that the hydrogel-forming compounds are prior art elements and would therefore be expected and predicted to form hydrogels when used in combination with a reasonable expectation of success (MPEP § 2144.06(I)). Here, the reasonable expectation of success merely requires the null hypothesis expecting each component to perform its art-recognized function.
No evidence of unexpected results: It is the Examiner’s understanding that Applicant is alleging the existence of unexpected results commensurate in scope with the requirements set forth at MPEP § 716.02 (see, e.g., Reply filed 12/24/2025 at 14 at 1st full ¶ to 15 at 3rd full ¶, referring to Figures and data of record.). However, to establish unexpected results, the allegations must be timely and supported by objective evidence (see, e.g., 37 C.F.R. 1.132; see MPEP §§ 716.01, 716.01(a), 716.01(c)); to be of probative value the proffered evidence must be related to the claimed invention (see MPEP §§ 716.01(b), discussing nexus requirement and noting that "[w]here the offered secondary consideration actually results from something other than what is both claimed and novel in the claim, there is no nexus to the merits of the claimed invention"); the evidence must establish that the expected results occur to an unexpected extent (see, e.g., MPEP § 716.02(a)(I)), on the basis of statistically and practically significant evidence (see, e.g., MPEP § 716.02(b)(I)), which is fully explained (see, e.g., MPEP § 716.02(b)(II)), commensurate in scope with the claimed invention (see, e.g., MPEP § 716.02(d)), and wherein a comparison of the claimed invention with the closest prior art of record is provided (see, e.g., MPEP § 716.02(e)). Furthermore, even if evidence satisfying MPEP §§ 716.02, 716.02(a), 716.02(b), 716.02(d), and 716.02(e) is set forth on record, such evidence may not be sufficient to rebut prima facie obviousness because the evidence of expected and unexpected results must be weighed (see, e.g., MPEP § 716.02(c)(I)) and the totality of the record considered (see, e.g., MPEP §§ 716.01(d), 716.02(f)), including teachings in the prior art and evidence of expected results which weigh in favor of a determination of obviousness (see, e.g., MPEP § 716.02(c)(II)). Here, no evidence of unexpected results commensurate in scope with the requirements of MPEP § 716.02 have been placed on record to date at last because: No evidence commensurate in scope with the claimed invention has been placed on record (see, e.g., MPEP § 716.02(d)), no statistically and practically significant evidence showing an advantage over the closest prior art of record has been provided (see, e.g., MPEP § 716.02(e)), and the limited data of record suggests that the claimed invention merely achieves the predicted and expected result suggested in view of the prior art (i.e., the null hypothesis that hydrogel-forming compounds would simply form hydrogels as expected), which weighs in favor of a determination of obviousness (see, e.g., MPEP § 716.02(c)(II)). Accordingly, no evidence of unexpected results has been placed on record to date.
Accordingly, all applicable arguments have been fully considered but not found persuasive. Therefore, the rejection is maintained as revised above. All revisions were necessitated by Applicant amendment.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
US 2007/0157967 A16 (Jul. 12, 2007; Mershin et al) discloses a product comprising surfactant peptides (plural), selected from a group consisting of Formulas 1-10, which includes sequences of form (ϕ)m(+)n and (ϕ)m(-)n, wherein (ϕ) may be alanine; (+) may be lysine or arginine; (-) may be aspartic acid or glutamic acid; m is ≥5; and n is ≥1 (see, e.g., US’967 at claims 1-3). All amino acids disclosed are understood to encompass L-amino acids.
US 7846445 B27 (Dec. 7, 2010; Schellenberger et al.) teaches and discloses a peptide-based PEG alternative. Specifically, US’445 identifies the utility and shortcomings of PEG and PEGylation in the protein arts (see, e.g., US’445 at col. 1 at line 56 to col 2 at lines 60, col 38 at lines 45-50), and additionally discloses a protein “module” that can be utilized as a peptide-based recombinant PEG (“rPEG”) (see, e.g., US’445 at col 77 at lines 1-25, Fig. 5, Fig. 6, col 17 at lines 18-55, col 32 at lines 50-61,SEQ ID NOs: 96 and 107), including modules comprised of only glycine and serine (see id.; see esp id. at SEQ ID NO: 107).
US 12,226,5468 (Feb. 18, 2026) claims related embodiments that lack Substructure III (see, e.g., US’546 at claims).
US 20130202711 A19 (Aug. 8, 2013; Kataoka et al.) pertains to vesicles formed by combining two different diblock polymers, wherein each polymer comprises a hydrophilic portion and charged portion (see, e.g., US’711 at title, abs, Fig. 3, claims 1-26).
US 2014/028686510 (Sep. 25, 2014; Deming et al.) pertains to the usage of amphiphilic diblock copolypeptide hydrogels, which are referred to as “DCH” (see, e.g., US’865 at ¶[0006]), and US’865 discloses the use of “DCH” as gels and scaffolds, including in CNS applications (see, e.g., US’865 at ¶¶[0006]-[0007], [0025], [0029]-[0033]). Such disclosures are pertinent because US’865 explicitly identifies that the phrase “a DCH” or “the DCH” may “include[] multiple DCH, e.g., 2, 3, 4, 5 or more DCH, which can be the same or different” (see, e.g., US’865 at ¶[0057]).
US 20150258219 A111 (Sep. 17, 2015; Kataoka et al.) pertains to vesicles formed by combining two different diblock polymers, wherein each polymer comprises a hydrophilic portion and charged portion (see, e.g., US’219 at title, abs, claims 15-27).
US2016/000240512 (Jan. 7, 2016) discloses MO65(L0.5F0.5)20 and similar sequences (see, e.g., US’405 at ¶[0019]).
Harada et al. (Formation of Polyion Complex Micelles in an Aqueous Milieu from a Pair of Oppositely-Charged Block Copolymers with Poly(ethylene glycol) Segments, Macromolecules, vol. 28:5294-5299 (1995); hereafter “Harada”; cited in IDS filed 04/05/2022 as cite no. CB) discloses the complexation of oppositely-charged block copolymers, namely PEG-polylysine and PEG-polyaspartic acid (see, e.g., Harada at title, abs, Fig. 8 on 5298). Harada concludes
Mixing of oppositely charged block copolymers in an aqueous milieu led to the spontaneous formation of polyion complex micelles having a spherical shape with a considerably narrow distribution. As for other block copolymer micelles, these polyion complex micelles may have a corona of hydrophilic PEG segments which surround the core of the polyion complex of cationic and anionic segments. It is well-known that various charged substances such as ions, proteins, and nucleic acids are selectively concentrated in polyion complex coacervates through electrostatic interaction. This feature is quite feasible for utilizing the polyion complex micelles made from block copolymers as vehicles for charged compounds in the field of drug discovery.
(see, e.g., Harada at 5298-5299 at bridging ¶)
Accordingly, mixing oppositely charged block copolymers to predictably form polyion complexes is not a point of novelty.
Insua et al. (Polyion complex (PIC) particles: Preparation and biomedical applications, European Polymer Journal, vol. 81:198-215 (June 2016), doi: 10.1016/j.eurpolymj.2016.06.003. PMID: 27524831; PMCID: PMC4973809. (IDS filed 04/05/2022 as cite no. CC; hereafter “Insua”) discloses that “[o]ppositely charged polyions can self-assemble in solution” and form “polyion complex (PIC) particles” (see, e.g., Insua at abs), and that such polyions may include proteins (see, e.g., id. at 198 at § 1). The PIC assembly is illustrated generically for any anionic and cationic polymers at figure 3 (see, e.g., Insua at Fig. 3 on 201).
Srivastava et al. (Gel phase formation in dilute triblock copolyelectrolyte complexes, Nature Communications, vol 8:14131. doi: 10.1038/ncomms14131, 9 pages (Feb 23, 2017); hereafter “Srivastava”; IDS filed 04/05/2022 as cite no. CF) discusses gel formation using diblock and triblock copolyelectrolytes (see, e.g., Srivastava at title, abs, Fig. 2 on 4, reproduced in part below):
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Accordingly, the formation of gels using diblock or triblock copolyelectrolytes is not novel or surprising, but is instead the expected and predicted result.
Captain et al (Methionine sulfoxide and phosphonate containing double hydrophilic block copolypeptides and their mineralization of calcium carbonate. J. Polym. Sci. Part A: Polym. Chem., 54: 3707-3712 (2016), https://doi.org/10.1002/pola.28264 (IDS filed 9/28/2021 as cite no. CK) discloses diblock copolypeptides (see, e.g., id. at title, abs, Table 1 on 3709).
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new or revised ground(s) of rejection presented in this Office action. Accordingly, 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 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RANDALL L BEANE whose telephone number is (571)270-3457. The examiner can normally be reached Mon.-Fri., 7 AM to 2 PM ET.
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, Lianko G. Garyu can be reached at (571) 270-7367. 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.
/RANDALL L BEANE/Primary Examiner, Art Unit 1654
1 “MOA” is understood to refer to L-methionine sulfoxide-stat-L-alanine
2 Deming et al., Conformation-Directed Formation of Self-Healing Diblock Copolypeptide Hydrogels via Polyion Complexation, Journal of the American Chemical Society 2017 139 (42), 15114-15121, DOI: 10.1021/jacs.7b08190 (hereafter “Demining”, published Oct. 4, 2017).
3 Wollenberg et al., Injectable polypeptide hydrogels via methionine modification for neural stem cell delivery. Biomaterials. 2018 Sep;178:527-545. doi: 10.1016/j.biomaterials.2018.03.057. Epub 2018 Apr 5. PMID: 29657091; PMCID: PMC6054810; hereafter “Wollenberg”.
4 “MOA” is understood to refer to L-methionine sulfoxide-stat-L-alanine
5 poly(L-methionine sulfoxide0.9-stat-L-alanine0.1)170-b-poly(L-leucine)n
6 Cited in previous action
7 Cited in previous action
8 Cited in previous action
9 Cited in previous action
10 Cited in previous action
11 Cited in previous action
12 Cited in previous action
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