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 on 28 October, 2022, claims domestic benefit to US provisional application nos. 63/320,009, filed on 15 March, 2022, 63/320,016, filed on 15 March, 2022, 63/274,316, filed on 01 November, 2021, and 63/273,741, filed on 29 October, 2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 01, December, 2022 has been considered by the examiner.
The information disclosure statement (IDS) submitted on 16, May, 2023 has been considered by the examiner.
The information disclosure statement (IDS) submitted on 20, July, 2023 has been considered by the examiner.
The information disclosure statement (IDS) submitted on 04, September, 2024 has been considered by the examiner.
The information disclosure statement (IDS) submitted on 04, September, 2024 has been considered by the examiner.
The information disclosure statement (IDS) submitted on 22, October, 2025 has been considered by the examiner.
Status of Application, Amendments, and/or Claims
The response filed on 27 January, 2026 has been entered in full. These are the amended claims of the original claim set received on 28 October, 2022. In the amendment, claims 1, 3, 5, 6, 26, 27, and 29 are amended and claim 2 is cancelled.
Claim 25 was withdrawn without traverse, to a restriction requirement in a response filed on 27 January 2026, however, upon further consideration the restriction requirement is dropped and claim 25 is rejoined for consideration.
Therefore, claims 1, and 3-30 are pending and are the subject of this Office Action.
Drawings
The drawings are objected to as failing to comply with 37 CFR 1.84(p)(5) because they do not include the following figures mentioned in the description: Fig 1, Fig 2, and Fig 4A. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 3-6, 8, 12, 13, 15-19, and 25 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Steenblock and Fahmy (2008) A Comprehensive Platform for Ex Vivo T-cell Expansion Based on Biodegradable Polymeric Artificial Antigen-Presenting Cells Molecular Therapy (16)4 765-772 (hereafter Steenblock and Fahmy).
In regards to claim 1 Steenblock and Fahmy anticipate a hydrogel microparticle which has utility in efficient polyclonal and antigen specific T cell stimulation (activation) and expansion (cell growth and proliferation) (abstract). Further Steenblock and Fahmy anticipate the hydrogel microparticle containing IL-2 (pg.771, col 1, lines 22-28).
In regards to claim 3 and 4 Steenblock and Fahmy anticipate the target cell being a T-cell (lymphocyte) (pg.765, col 2, line 38 – pg.766, col 1, line 1).
In regards to claim 5 Steenblock and Fahmy anticipate the hydrogel microparticle comprising IL-2 (pg.771, col 1, lines 22-28).
In regards to claim 6 Steenblock and Fahmy anticipate the hydrogel microparticle is a matrix formed by PLGA (polymerized lactide and glycolide monomers)(pg.771, col 1, lines 16-28).
In regards to claim 8 Steenblock and Fahmy anticipate the hydrogel microparticle being biodegradable (pg.765, col 2, line 38 – pg.766, col 1, line 1).
In regards to claim 12 Steenblock and Fahmy anticipate the hydrogel microparticle being composed of the biodegradable monomer poly(lactic-co-glycolic) acid (pg.766, col 1, lines 11-15).
In regards to claim 13 Steenblock and Fahmy anticipate the hydrogel microparticle monomer containing Avidin-palmitate conjugates to functionalize the surface and allow the attachment of biotinylated binding motifs (pg.766, col 1, lines 15-25 / Figure 1).
In regards to claim 15 Steenblock and Fahmy anticipate the hydrogel monomer composed of Avidin-palmitate further allows it to bind to biotinylated Anti-CD3 or MHC dimer ligands as well as a biotinylated CD28 ligand (bifunctional) (Figure 1)).
In regards to claim 16 Steenblock and Fahmy anticipate a circular hydrogel microparticle which is functionalized on the surface (Figure 2).
In regards to claim 17 Steenblock and Fahmy anticipate a degradable matrix of PLGA (pg.766, col 1, lines 11-15).
In regards to claim 18 Steenblock and Fahmy anticipate a degradable matrix configured to be broken down chemically as PLGA is degraded in culture with other cells (pg.771, col 1, lines 49-59).
In regards to claim 19 Steenblock and Fahmy anticipate the hydrogel microparticle having IL-2 encapsulated within the degradable matrix (pg.771, col 1, lines 22-28).
In regards to claim 25 Steenblock and Fahmy anticipate a method of efficient polyclonal and antigen specific T cell stimulation (activation) and expansion (cell growth and proliferation) by culturing the T-cell with a hydrogel microparticle loaded with IL-2 (pg.771, col 1, line 49- pg.771, col 2, line 9).
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.
Claims 7 and 9-11 are rejected under 35 U.S.C. 103 as being unpatentable over Steenblock and Fahmy as applied to claims 1, 6, 7 above, and further in view of Kevlahan et al. (WO2018175408) (hereafter Kevlahan (2018)) as evidenced by Chandra and Rustgi, (1998) Biodegradable polymers Progress in Polymer Science (23) 7 pgs. 1273-1335 (hereafter Chandra and Rustgi).
Steenblock and Fahmy teach a biodegradable PLGA hydrogel microparticle containing IL-2 for efficient polyclonal and antigen specific T cell stimulation and expansion as outline above.
Steenblock and Fahmy fail to teach the polymerized monomer being from the selected list of claim 7, and the biodegradable monomer being a monosaccharide, disaccharide, polysaccharide, peptide, protein, or protein domain of claim 9-11.
Kevlahan (2018) however, teaches a hydrogel can be formed from a list of synthetic or natural polymers which are biocompatible and optionally can be degradable through various mechanisms.
In regards to claim 7 Kevlahan (2018) teaches a hydrogel can be formed by synthetic polymers including poly(methyl methacrylate) (polymerized methyl methacrylate) and poly(hydroxyethoxyethyl methacrylate) (polymerized hydroxyethoxyethyl) (pg.2 lines 28-40).
In regards to claim 9 Kevlahan (2018) teaches a hydrogel can be formed by natural polymers which including polysaccharides, peptides and fibrous protein-based biopolymers (pg.2, lines 25-28). Chandra and Rustgi teach that natural biodegradable polymers include , polysaccharides, polypeptides, and polypeptides of natural origin (proteins) (section 2, pgs. 1275-1283), thus Kevlahan (2018) encompasses biodegradable polymers as evidenced by Chandra and Rustgi.
In regards to claim 10 Kevlahan (2018) teaches a hydrogel can be formed from a list of natural polymers including collagen (pg.2, lines 25-28).
In regards to claim 11 Kevlahan (2018) teaches a hydrogel can be formed from a list of natural polymers including carboxymethylcellulose (structural polysaccharide) (pg.2, lines 25-28).
Thus, Steenblock and Fahmy teach a biodegradable PLGA hydrogel microparticle containing IL-2 for efficient polyclonal and antigen specific T cell stimulation and expansion and Kevlahan (2018) teaches the success of hydrogels made from synthetic and natural polymers (polymerized monomers) including poly(methyl methacrylate), poly(hydroxyethoxyethyl methacrylate), collagen, and carboxymethylcellulose for biocompatible and optionally degradable microparticles. Therefore, a person of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to combine the teachings of Steenblock and Fahmy with the teachings of Kevlahan (2018) with a reasonable expectation of success to develop a hydrogel comprising a molecule to support cell growth, increase cell proliferation, and/or increase the activation of a target cell which the monomer used for the synthesis of the particle is substituted with one taught in Kevlahan (2018) to maintain biocompatibility, and optionally biodegradability through monomer dependent mechanisms.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Steenblock and Fahmy as applied to claims 1, 6, and 13 above, and further in view of Klechevsky et al. (WO2019018727, of record IDS 10/22/2025).
Steenblock and Fahmy teach an IL-2 hydrogel microparticle synthesized from a PLGA monomer that supports cell growth, increases cell proliferation, and/or increases activation of a target cell wherein the molecule is an interleukin and further wherein the polymerized monomer (PLGA) is functionalized as outlined above. Steenblock and Fahmy also teach the use of an avidin-palmitate conjugate to functionalize the hydrogel surface and allow for the attachment of binding moiety (pg.766, col 1, lines 15-25 / Figure 1).
Steenblock and Fahmy fails to teach the specific use of acrylate or acrylamide.
Klechevsky, however, uses a similar strategy of functionalization though integration of a surface reactive group/ linker to allow the binding moiety to bind to the hydrogel surface (pg.14 lines 25-27) and further suggest the use of acrylate (pg.14 lines 14-16).
Thus, Steenblock and Fahmy discloses a hydrogel particle which comprises a molecule to modulate a T-cell and contains an interleukin which is functionalized on the surface, and Klechevsky teaches acrylate as a reactive group which could achieve this function. Therefore, a person of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to use the teachings of Steenblock and Fahmy with the substitution of acrylate taught in Klechevsky with a reasonable expectation of success to develop a hydrogel particle which can modulate T-cells and which is functionalized by acrylate on the surface.
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Steenblock and Fahmy as applied to claims 1 and 17 above, and further in view of Tran et al. (2020) Multifunctional poly(disulfide) hydrogels with extremely fast self-healing ability and degradability. Chemical Engineering Journal (394) 124941 (hereafter Tran).
Steenblock and Fahmy teach a degradable hydrogel comprising a molecule that supports cell growth, increases cell proliferation, and/or increases activation of a target cell wherein the molecule is an interleukin as outlined above.
Steenblock and Fahmy fail to teach the hydrogel particle further comprising at least one disulfide crosslink.
Tran, however, teaches “that use of disulfide bonds to form crosslinked hydrogel networks has emerged as a suitable strategy for obtaining self-healing and/or degradable hydrogels, because these bonds are highly responsive to various stimuli” (pg.2, col 1, lines 10-14).
Thus, Steenblock and Fahmy discloses a degradable hydrogel particle which comprises a molecule to modulate a T-cell and contains an interleukin, and Tran teaches that disulfide crosslinking allows for self-healing and/or degradable hydrogels. Therefore, a person of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to combine the teachings of Steenblock and Fahmy with the teachings of Tran with a reasonable expectation of success to develop a hydrogel particle which can modulate T-cells and which has improved degradability supported by disulfide bonds.
Claims 21-23 are rejected under 35 U.S.C. 103 as being unpatentable over Steenblock and Fahmy as applied to claim 1 above, and further in view of Ma et al. (2020) Multilayer Injectable Hydrogel System Sequentially Delivers Bioactive Substances for Each Wound Healing Stage ACS Appl. Mater. Interfaces (12) 29787-29806 (hereafter Ma).
Steenblock and Fahmy teach a hydrogel comprising a molecule that supports cell growth, increases cell proliferation, and/or increases activation of a target cell wherein the molecule is an interleukin as outlined above.
Steenblock and Fahmy fail to teach the plurality of layers of the hydrogel particle in which each layer contains the same or different molecules.
Ma, however, teaches a multilayer hydrogel system which is composed of three different hydrogel layer the outer most layer is sodium alginate/ bioglass composite hydrogel, the next layer is a sodium alginate microparticle, and the inner most layer is a PLGA microsphere (pg.29789, col 1, lines 12-25). Further it is taught that this multilayered system allowed for time-controlled release of the active molecules within each layer, and further they discuss the important of biodegradation in this process (pg.29789, col 1, lines 25-29/ pg.29802, col 1, lines 30-34 and 52-58). Ma also suggests the use of this multilayered system in various contexts and discuss how the system can be adapted just by changing the active molecules to prompt various kinds of tissue regeneration (pg.29789, col 1, lines 29-31).
Thus, Steenblock and Fahmy discloses a hydrogel particle which comprises a molecule to modulate a T-cell and contains an interleukin, and Ma teaches a multilayer hydrogel system for controlled release of active molecules. Therefore, a person of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to combine the teachings of Steenblock and Fahmy with the teachings of Ma with a reasonable expectation of success to develop a hydrogel particle which can modulate T-cells and wherein the hydrogel particle has a plurality of layers for to control the time of release of the molecules in the hydrogel.
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over Steenblock and Fahmy as applied to claim 1 above, and further in view of Kevlahan et al. (US 2017/0081636, of record IDS 10/22/2025) (hereafter Kevlahan (2017)).
Steenblock and Fahmy teach a hydrogel comprising a molecule that supports cell growth, increases cell proliferation, and/or increases activation of a target cell wherein the molecule is an interleukin as outlined above.
Steenblock and Fahmy fail to teach the hydrogel particle further comprising a magnetic material embedded and/or encapsulated within the matrix which are capable of being attracted or repelled by a magnetic field or gradient introduced by a magnet.
Kevlahan (2017), however, teaches the use of a hydrogel particle targeted towards a T-cell functionalized with molecules which induce biochemical or morphological change (pg.3, paragraphs 0024). Further Kevlahan (2017) teaches these hydrogel particles can also contain magnetic particles to allow for separation by magnet after T-cell expansion (pg.2, paragraphs 0018 and 0019).
Thus, Steenblock and Fahmy discloses a hydrogel particle which comprises a molecule to modulate a T-cell and contains an interleukin, and Kevlahan (2017) teaches the addition of magnetic particles to allow for T-cell separation after expansion. Therefore, a person of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to combine the teachings of Steenblock and Fahmy with the teachings of Kevlahan (2017) with a reasonable expectation of success to develop a hydrogel particle which can modulate T-cells and which has a mechanism for improved T-cell separation after modulation.
Claims 26-30 are rejected under 35 U.S.C. 103 as being unpatentable over Kevlahan(2018) as evidenced by Azevedo and Reis (2005) Understanding the enzymatic degradation of biodegradable polymers and strategies to control their degradation rate Biodegradable systems in tissue engineering and regenerative medicine (ch.12) (hereafter Azevedo and Reis).
In regards to claims 26-29 Kevlahan (2018) teaches various embodiments of hydrogels which can target a list of immune cells including T-cells and NK cells, and further can contain different molecules including interleukins and TNF-α as outlined above.
In regards to claim 30 the different embodiments of hydrogels taught in Kevlahan (2018) would have different degradation rates as evidenced by Azevedo and Reis which teach that polymer composition and surface modifications impact its degradation (pg. 191, lines 1-10), thus the various polymers outlined in Kevlahan (2018) as potential hydrogels would result in different degradation rates and therefore, Kevlahan (2018) teaches multiple hydrogels with different degradation rates.
The kits do not preclude the structures.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 5, 6, 7, 15, 17, 19, 20, and 24 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4, 8, and 9 of U.S. Patent No. 12,134,779 in view of Steenblock and Fahmy, and Kevlahan (2017).
Claims 1 and 8 of the U.S. Patent recites a magnetic capture hydrogel particle, comprising a magnetic material embedded and/or encapsulated therein, such that the hydrogel particle is capable of being attracted to or repelled by a magnetic field and the addition of a ligand capable of binding the hydrogel matrix to a capture molecule and further wherein the capture target molecule is selected from a group consisting of CD137, CD137L, and IL-15 (member of the tumor necrosis superfamily or an interleukin) as claimed in instant application claims 1, 5, and 24.
Claim 2 of the U.S. patent recites the magnetic capture hydrogel of claim 1 matrix comprises a polymerized monomer and a bifunctional monomer as clamed in instant application claims 6 and 15
Claim 3 of the U.S. patent recites the magnetic hydrogel of claim 2 comprises an acrylate as claimed in instant application claims 13 and 14.
Claim 4 of the U.S. patent recites the monomer is selected from a list of potential monomers, this list is identical to the list of monomers claimed in instant application claim 7.
Claim 9 of the U.S. patent recites the hydrogel matrix which is embedded with a target molecule is degradable as claimed in instant application claims 17 and 19.
Claim 10 of the U.S. patent recites the degradable matrix includes at least one disulfide crosslink as claimed in instant application claim 20.
Claim 1 of the U.S. Patent fails to teach the molecule comprising an interleukin and/or a member of the tumor necrosis factor superfamily necessary for dependent claims 2, 3, 4, 9, and 10 of the issued patent to meet the limitations of the instant claims 1, 5, 6, 7, 15, 17, and 24. Steenblock and Fahmy however teach a hydrogel particle loaded with IL-2 to increase the viability and proliferative capacity of T cells (pg.767, col 2, lines 14-15).
Thus, the issued patent recites claim to a magnetic capture hydrogel comprising an embedded and/or encapsulated magnetic material which can be attracted to or repelled by a magnetic field, a target molecule and further, the structural limitation claimed in the instant application. Steenblock and Fahmy teach that the inclusion of IL-2 in the hydrogel increases the viability and proliferative capacity of T cells. Therefore, a person of ordinary skill in the art before the effectively filed date would have found it obvious to use the teachings of Steenblock and Fahmy to modify the magnetic capture hydrogel of the U.S. patent to get the all the embodiments of hydrogels claimed in claims 1, 5, 6, 7, 15, 17, and 24 of the instant application.
It is noted by the examiner that Claim 1 of the U.S. patent, while meeting all of the limitation of claim 1 of the instant application in view of Steenblock and Fahmy, includes magnetic material which is not claimed in claim 1 of the instant application, however, Kevlahan (2017) teaches a hydrogel loaded with magnetic particles and further teaches the complex can be spherical and have a diameter before 1-20μm in diameter (paragraph 0010) thus making the addition of magnetic particles to any of the claimed hydrogel in the instant application obvious to one of ordinary skill in the art on or before the effective filing date.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DASIA A ALDARONDO whose telephone number is (571)272-1977. The examiner can normally be reached on Monday - Thursday from 7am to 4pm and Friday 7am to 11am.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama, can be reached at telephone number (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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/D.A.A/Examiner, Art Unit 1647 /JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647