DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
The instant application, filed 05/05/2023, claims domestic benefit to US provision application 63/341,174, filed 05/12/2022.
Claim Status
The Amendment, filed on 08/24/2026, is acknowledged in which:
Claims 1-3, 7, 10-11, 13 and 17-20 are currently amended.
Claims 4-6, 8-9, 12, and 14-16 are original.
Claims 1-20 are pending in the instant application and are examined on the merits herein.
Withdrawn Objections and Rejections
In the office action dated 05/21/2026,
The specification was objected to for informalities in the text and tradenames or marks used in commerce without appropriate symbols. Applicant’s submission of an amendment to the specification with appropriate corrections has overcome the objections and the objections are withdrawn.
Claims 2, 3, 10, and 13 were objected to for typographical errors. Applicant’s amendment to the claim has overcome the objection and the objection is withdrawn.
Claims 7 and 17 were rejected for reciting an improper Markush grouping of alternatives. Applicant’s amendment to the claim to remove SEQ ID NO:9 has overcome the rejections and the rejections are withdrawn.
Claim 17 was rejected under 35 USC 112(b) for reciting a limitation with insufficient antecedent basis. Applicant’s amendment to the claim has overcome the rejection and the rejection is withdrawn.
Claims 7 and 17 were rejected under 35 USC 112(d) for failing to further limit the subject matter of the claim upon which it depends. Applicant’s amendment to the claims to remove SEQ ID NO:9 has overcome the rejections and the rejections are withdrawn.
Claims 1-6, 8-16, and 18-20 were rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. Applicant’s arguments, see Remarks (section 6), filed 08/24/2026, with respect to definition of a structural genus have been fully considered and are persuasive. Therefore, the rejections are withdrawn.
Claims 1-4 were rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 9 of U.S. Patent No. 9,498,539. Applicant’s arguments, see Remarks (section 12), filed 08/24/2026, with respect to instantly claimed peptidic ligands having binding affinity to a portion of an Fc constant region have been fully considered and are persuasive. Therefore, the rejections are withdrawn.
The following grounds of objections and/or rejections are either maintained or necessitated by applicant’s amendment to the claims. Please note: the text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
New - Claim Objections
Claim 10 is objected to because of the following informalities: a space is missing between “hydrogelpolymeric” (10(d), line 2). Appropriate correction is required.
Maintained Claim Rejections - 35 USC § 102
Claims 1-6 and 10-16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Pham (Biomater Sci. 2019;7(3):760-772) as evidenced by Zhang (Proc Natl Acad Sci USA. 1993;90(8):3334-3338).
Pham teaches a synthetic peptide derived from SpA (selected based on known affinity of parental peptide for IgG at approximately 20 nM) fused with self-assembling peptide (SAP) EAK with a GGGGS spacer (i.e. non-binding amino acid sequence within scope of a chain extender as defined in the instant specification; pg 6, lines 16-20), resulting peptide named Z15_EAK (Abstract; pg 761-762 spanning ¶; Figure 1). EAK peptides undergo sol-gel phase transition in the presence of salt, forming β fibril matrix (i.e. hydrogel; pg 760, Introduction, ¶ 1), each filament measuring 10-20 nm in diameter (i.e. nanoparticle) as evidenced by Zhang (Abstract). The one-site binding affinity (Kd or dissociation constant) of the gel-like coacervate generated by admixing Z15_EAK with EAK for IgG was determined to be 1.27 ± 0.14 μM (or 1.27 x 10-6 M) (Abstract). Flank and footpad injections (i.e. in situ hydrogel formation) of IgG800 admixed with Z15_EAK had greater retention of antibody in comparison with IgG800 delivered in EAK alone (Figures 5 and 6). Pham demonstrates that rather than trapping IgG through entanglements with polymer fibers, Z15_EAK facilitates an affinity mechanism by which the release kinetics of Fc-based biotherapeutics can be spatiotemporally controlled (Abstract; Figure 6; Discussion, ¶ 1).
Response to Arguments:
Applicant's arguments filed 08/24/2026 have been fully considered but they are not persuasive.
Applicant states:
“…[Pham] fails to disclose or suggest any sort of structural arrangement where a peptidic ligand is covalently coupled to a polymeric network…” (Remarks, pg 15, ¶ 3)
“While the Z15 domain is covalently linked to the EAK domain via a peptide bond, this covalent bond is the internal peptide backbone of the monomeric molecule itself and not a coupling of a peptidic ligand to a polymeric network.” (Remarks, pg 15, ¶ 5)
“…the monomeric units merely physically and non-covalently co-assemble to form a fibril matrix” (Remarks, pg 16, ¶ 1)
“The failure of Pham to anticipate the claimed invention is not made up for by the Zhang publication, which similarly confirms that EAK16 is a self-complementary oligopeptide that "spontaneously assembles" into a macroscopic membrane through non-covalent physical interactions” (Remarks, pg 16, ¶ 2)
“Under [claim 10] sequence, covalent attachment of the ligand to the network precursor (step(ii)) is a discrete act that necessarily precedes, and is chemically independent of, hydrogel/network formation (step(iv)).” (Remarks, pg 20, ¶ 1)
“Z15 and EAK are joined in a single solid-phase peptide synthesis to produce Z15_EAK as one continuous molecule; there is no subsequent, separate covalent step by which a ligand is immobilized onto a pre-existing or independently-provided “polymeric network precursor” (Remarks, pg 20, ¶ 2)
“In every disclosed embodiment, without exception, the polymeric network (e.g., HAKT, PEGOA4) and the peptidic ligand (e.g., FcL-1, FcL-2) are separately-synthesized species…the peptidic ligand is chemically grafted or conjugated as a distinct pendant group directly to a polymer backbone that exists” (Remarks, pg 18).
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., covalent assembly of the fibril matrix and conjugating distinct pendant groups directly to a polymer backbone) 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).
Briefly, the claims recite that the “peptidic ligand is covalently coupled to the polymeric network” (claim 1) and “covalently immobilizing the peptidic ligand to polymeric network precursors” (claim 10). By broadest reasonable interpretation, the covalent bond between Z15 and an EAK peptide precursor, as taught by Pham, is within scope of the instant claims requiring a covalent bond. The process of “immobilizing” as recited in the instant claims has been interpreted as satisfied by covalent binding because as currently claimed the precursors are described to be in aqueous solution (claim 10c) prior to hydrogel formation (claim 10d) (i.e. contrary to the basic definition of immobilization which implies holding in place). Moreover, a strict definition of what classifies a “polymeric network precursor” is not provided in the instant specification, therefore examiner has interpreted this to mean a molecule capable of forming a hydrogel polymeric network, which is anticipated by the EAK precursor as disclosed by Pham. Furthermore, as currently claimed, the polymeric network does not explicitly require covalent interactions between fibrils for hydrogel formation nor that the precursors and peptides be separately synthesized.
Maintained Claim Rejections - 35 USC § 103
Claims 7, 9, 17, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Pham as applied to claims 1 and 10 above, and further in view of Choe (Materials (Basel). 2016;9(12):994).
Regarding claims 7 and 17, Pham teaches claims 1 and 10 as discussed above.
Pham does not teach a peptidic ligand with identity to recited functional species.
Choe references studies that teach a variety of SpA mimic peptides and alternative peptides with IgG binding affinity with identity to the recited instant sequences (instant SEQ ID NOs: 1-4, 8, 10, and 12-13) (Table 2; Figure 2). Choe further teaches several of these Ab affinity ligands have been successfully immobilized on various solid supports for Ab binding (pg 8-10; Figure 5A).
It would be generally understood by a skilled artisan that these Fc-binding peptides as referenced by Choe would reasonably function the similarly in binding immunoglobins (i.e. art recognized suitability for an intended purpose) (See MPEP 2144.07). Therefore, it would be obvious to one of ordinary skill in the art that peptides with identity to those within scope of the instant claim as taught by Choe could be substituted for the SpA peptide as taught by Pham with a reasonable expectation of generating a protein-release system as instantly claimed (See MPEP 2143(I)(B)).
Regarding claims 9 and 20, Pham teaches claims 1 and 10 as discussed above.
Pham does not teach the use of two or more peptidic ligands.
Choe teaches that an antibody affinity column comprising FYWHCLDE and FYCHTIDE (instant SEQ ID NOs: 8 and 10, respectively) at a molar ratio of 2:1 showed synergistically enhanced binding affinity toward IgG (Kd = 0.7 μM) (pg 9, ¶ 3).
Therefore, it would be obvious to one of ordinary skill in the art that the Fc-affinity gel as taught by Pham can be modified to included two or more peptidic ligands and a skilled artisan would be motivated to do so because Choe teaches this can lead to synergistic improvements to Fc binding affinity and therefore a means to further fine tune the spatiotemporal release of Fc-based proteins.
Response to Arguments:
Applicant's arguments filed 08/24/2026 have been fully considered but they are not persuasive.
a) Applicant states:
“Choe publication is directed exclusively to affinity ligands immobilized on rigid solid supports… Choe discloses no hydrogel of any kind” (Remarks, pg 21, ¶ 3).
“Choe’s synergy data was generated using peptides immobilized on chromatographic resin – an entirely different physical format from Pham’s self-assembling fibril system – and Choe says nothing about how, or whether, two peptidic ligands could be incorporated into a self-assembling peptide network, let alone covalently coupled to an independently-sourced polymeric network” (Remarks, page 21-22 spanning ¶).
In response to applicant's argument that Choe does not teach a hydrogel and that resin based formats as taught by Choe are inherently different from self-assembling fibril system as taught by Pham, the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). Briefly, Pham teaches a fibril system comprising an Fc-binding ligand (Z15, a 15-amine acid sequence) and teaches successful IgG affinity in a hydrogel format. Pham, however, does not teach a ligand with identity to the claimed sequences. Choe teaches alternative small Fc-binding ligands within scope of the species recited in the instant claims. The office maintains "[a] person of ordinary skill in the art is also a person of ordinary creativity, not an automaton." KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 421, 82 USPQ2d 1385, 1397 (2007). "[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle." Id. at 420, 82 USPQ2d 1397. Office personnel may also take into account "the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at 418, 82 USPQ2d at 1396. Therefore, a skilled artisan could predictably substitute the Fc-affinity ligand as taught by Pham for one or more suitable Fc-affinity ligand alternatives as taught by Choe.
The reasonable expectation of success requirement refers to "the likelihood of success" in combining or modifying prior art disclosures to meet the limitations of the claimed invention. See Elekta Ltd. v. ZAP Surgical Sys., Inc., 81 F.4th 1368, 1375, 2023 USPQ2d 1100 (Fed. Cir. 2023) and Intelligent Bio-Sys., Inc. v. Illumina Cambridge Ltd., 821 F.3d 1359, 1367, 119 USPQ2d 1171, 1176 (Fed. Cir. 2016). Conclusive proof of efficacy is not required to show a reasonable expectation of success. OSI Pharm., LLC v. Apotex Inc., 939 F.3d 1375, 1385, 2019 USPQ2d 379681 (Fed. Cir. 2019). Briefly both references teach IgG affinity is maintained on various solid supports (i.e. hydrogels and resins) and Choe teaches the feasibility of using multiple ligands simultaneously, therefore there is a reasonable expectation that IgG affinity would be maintained to a certain extent when substituting one or more ligands.
Claims 8 and 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Pham as applied to claims 1 and 10 above, and further in view of Kim (Nanomaterials (Basel). 2021;11(2):471) and Abune (Trends Pharmacol Sci. 2021;42(4):300-312).
Pham teaches claims 1 and 10 as discussed above.
Pham does not teach the use of two or more different Fc-proteins for their protein release system.
Kim teaches sustained release of combination immunotherapy (antibodies blocking CTLA-4 and PD-1 signaling) from in situ crosslinked hydrogels injected ipsilateral to tumor tissue (Abstract; Scheme 1). Kim further teaches this formulation results in efficient and durable anticancer effects with reduced systemic toxicity compared to bolus delivery of free antibodies (Abstract; Figures 2 and 3).
Abune teaches several challenges associated with traditional hydrogels designed without molecular recognition including diffusion-controlled protein release kinetics largely dependent on the degree of hydrogel swelling and can lead to rapid diffusion or degradation-controlled release dependent on the degradation of hydrogel chains (pg 301, ¶ 3; Table 1). Protein release from affinity-based hydrogels can be slowed in comparison with traditional hydrogels (Figure 1). Abune teaches protein release kinetics of peptide-based affinity hydrogels can also be tuned by using peptides with different affinities (i.e. multiple ligands) (pg 305, ¶ 2). Abune further teaches that mounting evidence points to the need for more than one drug for the treatment of human diseases (e.g. cancer), and thus hydrogel-based therapeutics should be designed to control the release of multiple proteins (pg 307, ¶ 4).
Therefore, it would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention that an affinity based hydrogel as taught by Pham could be modified for dual immunotherapy treatment as taught by Kim (i.e. delivery of two or more Fc based therapeutics) and a skilled artisan would be motivated to do so because Kim teaches hydrogel based delivery improved antitumor effects of dual therapies while reducing off-target toxicity and Abune teaches affinity based hydrogels offer superior control in comparison to traditional hydrogels and diseases frequently need multiple proteins (i.e. different antibodies) for effective treatment. Furthermore, it would have been obvious to one of ordinary skill to combine a multitherapeutic approach as taught by the combined teachings of Pham and Kim with multiple peptidic ligands because Abune teaches using peptides with different affinities can be used to finetune temporal release for a longer therapeutic window (i.e. increasing overall time range of protein release by combining Fc ligands with weaker and stronger interactions).
Response to Arguments:
Applicant's arguments filed 08/24/2026 have been fully considered but they are not persuasive.
a) Applicant states:
“Kim discloses no peptidic ligand of any kind, let alone one covalently coupled to a polymeric network - its improved retention arises entirely from the physical density and degradation kinetics of the crosslinked matrix, not from any molecular-recognition or affinity mechanism. Kim therefore cannot supply, and is not cited for, the structural relationship missing from Pham. At most, Kim shows that co-delivering two therapeutic antibodies from a single hydrogel depot was known in the art, but in a system with no ligand-based architecture to combine with Pham's affinity mechanism in the first place” (Remarks, pg 23, ¶ 1).
“Abune does not teach or suggest how multiple Fe-proteins would be accommodated
within Pham's self-assembling fibril architecture, much less that doing so would require or
result in a peptidic ligand covalently coupled to an independently-sourced polymeric network” (Remarks, pg 23, ¶ 2).
“Notably, Abune's own discussion of peptide-mediated protein release (Abune: pp. 304-305) distinguishes between peptides chemically conjugated to a hydrogel matrix - the architecture the claims require - and peptides incorporated through the self-assembly of peptide amphiphiles, an architecture analogous to what Pham discloses. Abune's tunability statement, read in context, describes the former category and provides no reasonable expectation of success that multiple peptidic ligands could be incorporated into Pham's self-assembling system in the covalently-coupled-to-an-independent-network arrangement the claims require” (Remarks, pg 23-24 spanning ¶).
In response to applicant's argument regarding deficiencies in the analysis of the base claim (i.e. teaching of Pham and an independently-sourced polymeric network), these issues are addressed above, and therefore this argument, made on the basis that additional references do not cure the primary deficiency, is deemed unpersuasive. Moreover, as discussed above, the claimed invention need not be expressly suggested in any one or all of the references. Briefly, Kim teaches benefits of delivering of multiple therapeutics from a hydrogel-based delivery system and Abune teaches the further benefits of modifying such a hydrogel into an affinity-based controlled release system (i.e. as taught by Pham).
Regarding Abune’s tunability statement, the prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed…." In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004). See also MPEP § 2123. A skilled artisan would recognize, based on the teaching of Abune, that regardless of the specific method of covalently binding a peptidic ligand into a hydrogel (i.e. including a method as taught by Pham), protein:peptide ratio would still be a relevant concern for release kinetics and tuning based on peptide affinity would have applicability to either method.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HANNAH SUNSHINE whose telephone number is (571)270-7417. The examiner can normally be reached M-Th & Second Friday 8:30am-5pm 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, Joanne Hama can be reached at (571) 272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/HANNAH SUNSHINE/Examiner, Art Unit 1647 /JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647
