DETAILED ACTION
Status of the Claims
Claims 1-8, 11-13, 19-20 and 22 are pending in the instant application. Claims 9-10, 14-18 and 21 have been canceled by Applicant. Claims 1-8, 11-13, 19-20 and 22 are being examined on the merits in the instant application.
Advisory Notice
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
All rejections and/or objections not explicitly maintained in the instant office action have been withdrawn per Applicants’ claim amendments and/or persuasive arguments.
Priority
The instant Application is a U.S. national stage entry (371) of PCT/KR2021/003095 filed 03/12/2021. The instant Application claims priority to KR10-2020-0032035 filed 03/16/2020 and KR10-2020-0172631 filed 12/10/2020.
The U.S. effective filing date has been determined to be 03/12/2021, the filing date of PCT/KR2021/003095. Applicant's claim for a priority date of, 03/16/2020 and 12/10/2020, the filing date of documents KR10-2020-0032035 and KR10-2020-0172631, respectively, is acknowledged. Certified copies of the priority documents have been received in this National Stage application from the International Bureau (PCT Rule 17.2(a)). However no English translation of the priority documents have been provided such that the examiner can verify written description (112(a)) support therein. Accordingly, foreign priority to KR10-2020-0032035 and/or KR10-2020-0172631 cannot be afforded at this time.
Claim Rejections - 35 USC § 112(b)
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim 7-8 and 13 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claim 7-8 are rejected as being indefinite because the claims recites the phrase "the diameter of the hydrogel in deionized water" (in lines 1-2) which renders the claim indefinite because claim 1 has been amended to recite “the diameter (D) of the height axis of the hydrogel particle decreases by 30 to 99% in a state in which the hydrogel contacts the cell and covers the cell, compared to the diameter if the height axis of the hydrogel in a spherical state before the hydrogel contacts the cell.” where it is unclear which diameter (spherical diameter before contacting a cell or diameter in contact with a cell) is referenced in claims 7-8 which depend from claim 1. Appropriate clarification is required.
Claim 13 is rejected as being indefinite because the claim recites “wherein the hydrogel comprises a copolymer prepared by polymerizing components consisting of […] N-isopropylacrylamide […] acrylic acid.” However, Applicant has amended claim 1 to recite “wherein the hydrogel comprises “poly(N-isopropylacrylamide-co-methacrylic acid)” While claim 13 is a product by process, it is unclear how “polymerizing components consisting of […] N-isopropylacrylamide […] acrylic acid.” should result in comprises “poly(N-isopropylacrylamide-co-methacrylic acid)”. Appropriate clarification is required.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-8, 11-13 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over KEVLAHAN (WO 2018/175408 A1; published September, 2018) in view of Bachman et al.1 ("Ultrasoft, highly deformable microgels," 2015, RSC; Soft Matter, Vol. 11, pp. 2018-2028); SUNG (US 2018/0149641; published May, 2018).
Applicants Claims
Applicant claims a hydrogel particle being deformable and having at least one protein, which is capable of binding to a cell surface component of cancer cells or T-cells, bound to the surface of the hydrogel particle (instant claim 1).
Determination of the scope
and content of the prior art (MPEP 2141.01)
KEVLAHAN teaches that: “The present invention features a biocompatible hydrogel complex capable of binding to, activating, and expanding immune cell, e.g., T cells. In certain embodiments, the hydrogel complex can be dissolved, e.g., simply by reducing cation concentration, e.g., by introducing a chelating agent, enabling efficient production of large numbers of T cells for adoptive transfer systems and other uses of immune cells. Also provided herein are methods for producing hydrogel complexes and methods of generating expanded and/or activated immune cell, e.g., T cell, populations using the hydro gel complexes of the invention.” (p. 2, lines 13-19, see whole document). And that: “In one aspect, the invention features a particle including a complex including a hydrogel and a binding moiety, wherein the hydrogel includes a polymer; and the binding moiety is configured to bind a cell surface component of an immune cell.” (p. 2, lines 21-23).
KEVLAHAN teaches that: “In some embodiments, the cell surface component is CD2, CD3, CD19, CD24, CD27, CD28, CD31, CD34, CD45, CD46, CD80, CD86, CD133, CD134, CD135, CD137, CD160, CD335, CD337, CD40L, ICOS, GITR, HVEM, Galtectin 9, TIM-1, LFA-1, PD-LI, PD-L2, B7-H3, B7-H4, ILT3, ILT4, CDTL-4, PD-1, BTLA, MHC-I, MHCII, Delta-like ligand (e.g.,DLL-Fc, DLL-1, or DLL-4), WNT3, stem cell factor, or thrombopoietin.” (p. 3, lines 7-11)(instant claims 2-3). KEVLAHAN discloses that: “A binding moiety can be an antibody or antigen-binding fragment thereof. […] The antibody or antigen binding fragment thereof is, for example, anti-CD2, anti CD3, anti-CD19, anti-CD24, antiCD27, anti-CD28, anti-CD31, anti-CD34, anti-CD45, anti-CD46, anti-CD80, anti-CD86, anti-CD133, anti-CD134, anti-CD135, anti-CD137, anti-CD160, anti-CD335, anti-CD337, anti-CD40L, anti-ICOS, anti-GITR, anti-HVEM, anti-Galtectin 9, anti-TIM-1, anti-LFA-1, anti-PD-L1, anti-PD-L2, anti-B7-H3, anti-B7-H4, anti-lLT3, anti-lLT4, anti-CDTL-4, anti-PD-1, anti-BTLA, anti-MHC-I, anti-MHC-II, anti-Delta-like ligand (e.g., anti-DLL-Fc, anti-DLL-1, or anti-DLL-4), anti-WNT3, anti-stem cell factor, or anti-thrombopoietin. In some embodiments, the antibody or antigen-binding fragment thereof is anti-CD2, anti-CD3, anti-CD27, anti-CD28, anti-CD46, anti-CD80, anti-CD86, anti-CD134, anti-CD137, anti-CD160, anti-CD40L, anti-I COS, anti-G ITR, anti-HVEM, anti-Galtectin 9, anti-TIM-1, anti-LFA-1, anti-PD-L1, anti-PD-L2, anti-B7-H3, anti-B7 H4, anti-IL T3, anti-lLT4, anti-CDTL-4, anti-PD-1, anti-BTLA, anti-MHC-I, or anti- MHC-I1.” [emphasis added](p. 3, line 35; p. 4, lines 1-12)(instant claims 4-5).
KEVLAHAN teaches that: “The shape of the structure may be any suitable shape, such as elongated like a wire, tubular, i.e., having a lumen, planar, or spherical. In some embodiments, the complex can have a surface configured to replicate the immune synapse between an antigen presenting cell and a T cell. Immune synapses can range in size from less than 50 nm to about 20 μm. In some embodiments, the complex of the present invention is a particle, e.g., that is spherical. In most embodiments, the diameter is less than 1,000 μm. For example, the diameter of the complex can be between 50 nm and 20 μm (e.g., between 100 nm and 15 μm, between 200 nm and 14 μm, between 500 nm and 13 μm, between 1 μm and 12 μm, or about 10 μm). For example, the complex can be the size of antigen presenting cells, such as dendritic cells or macrophage, which range from about 10-20 μm. Alternatively, the complex can include a larger matrix, such as a porous scaffold, which can be mechanically exposed, e.g. dipped, into a suspension of cells. Methods for synthesizing such scaffolds, including by using alginate, are known in the art.” (p. 19, lines 9-20)(instant claims 7-8).
KEVLAHAN teaches that “Hydrogels of the
invention can be formed from natural polymers, synthetic polymers, and copolymers thereof.” and including “poly(N-isopropylacrylamide) (pNIPAAM), […] poly(methyl methacrylate) […] and any combination thereof.” (p. 16, lines 18-21, 25-35)(instant claim 1, “wherein the hydrogel comprises poly(N-isopropylacrylamide-co-methacrylic acid)(poly(NIPAM-co-MAAc)”.
KEVLAHAN does not expressly disclose that the hydrogel is “deformable,” however, KEVLAHAN teaches that: “In some embodiments, the hydrogel has an elastic modulus of less than 1 gigapascal (GPa), e.g., 0.8 GPa, 0.6 GPa, 0.4 GPa, 0.2 GPa, 0.1 GPa, 0.08 GPa, 0.06 GPa, 0.04 GPa, 0.02 GPa, 0.01 GPa, 0.008 GPa, 0.006 GPa, 0.004 GPa, 0.002 GPa, 0.001 GPa, 0.0008 GPa, 0.0006 GPa, 0.0004 GPa, 0.0002 GPa, or 0.0001 GPa. In some embodiments, the hydrogel has an elastic modulus of less than 100,000 pascals (Pa)." (p. 5, lines 26-30). KEVLAHAN discloses that: “The hydrogel complex can have an elastic modulus of less than 100,000 Pa. In some embodiments, the binding moiety binds to a cell surface component of a T cell.” (p. 9, lines 12-14, also see [0118] & [0119] discussing the elastic modulus of alginic-acid-based polymeric moiety). MPEP §2144.05(I) - In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. “an elastic modulus of less than 100,000 Pa” overlaps with “an elastic modulus at 25 °C in the range of 0.01 Pa to 100 Pa.” (instant claim 22).
Ascertainment of the difference between
the prior art and the claims (MPEP 2141.02)
The difference between the rejected claims and the teachings of KEVLAHAN is that KEVLAHAN does not expressly teach (1) a recombinant protein or aptamer capable of binding PD-L1, PD-1, CTLA-4 and CD137 (instant claim 6); (2) the main monomer is N-isopropylacrylamide and the comonomer is acrylic acid (i.e. poly(N-isopropylacrylamide-co-acrylic acid)(poly(NIPAM-co-AAc) crosslinked with N,N’-methylene-bis-acrylamide (MBA)(instant claims 10-12 14 and 15); or (3) the amount of main monomer, comonomer and crosslinker by weight in the hydrogel (instant claim 13).
Regarding instant claim 6, KEVLAHAN clearly teaches “recombinant human IL-2” (Examples 4-6) and teaches that: “In one aspect, the invention features a particle including a complex including a hydrogel and a binding moiety, wherein the hydrogel includes a polymer; and the binding moiety is configured to bind a cell surface component of an immune cell.” and clearly teaches the cell surface component is PD-L1, PD-1, CTLA-4 and CD137, among others (p. 3, 2nd paragraph). Therefore, it would have been prima facie obvious to utilize a recombinant protein capable of binding the cell surface component PD-L1, PD-1, CTLA-4 and/or CD137.
Bachman et al. teaches that: “Most commonly, thermo and pH-responsive poly(N-isopropylacrylamide) (pNIPAm) microgels can be fabricated by precipitation polymerization in the presence of the co-monomer acrylic acid (AAc). Traditionally pNIPAm microgels are synthesized in the presence of a crosslinking agent, such as N,N’-methylenebisacrylamide (BIS), however, microgels can also be synthesized under ‘crosslinker free’ conditions. The resulting particles have extremely low (<0.5%), core-localized crosslinking resulting from rare chain transfer reactions. AFM nanoindentation of these ultralow crosslinked (ULC) particles indicate that they are soft relative to crosslinked microgels, with a Young's modulus of ~10 kPa.” (abstract, see whole document)(instant claim 1, “wherein the hydrogel comprises poly(N-isopropylacrylamide-co-methacrylic acid) .
SUNG teaches “According to an aspect, there is provided a biochip including a hydrogel functional layer on which a binding mediator is formed and of which physical properties are changed by a reaction between target protein to be introduced and the binding mediator; and a transducer configured to deliver a displacement signal corresponding to a change in the physical properties of the hydrogel functional layer to an analysis instrument, wherein the reaction is multivalent bindings between the target protein and the binding mediator, and de-swelling occurs in at least a portion of the hydrogel functional layer by the multivalent bindings.” ([0009], see whole document). SUNG teaches that: “The hydrogel functional layer may include a copolymer formed of main monomer and comonomers. The main monomer may be one of N-isopropylacrylamide, poly(N-acryloylglycinamide), hydroxypropylcellulose, poly(vinylcaprolactame) and polyvinyl methyl ether. The comonomers may be at least one of allylamine (AA), dimethylaminoethyl methacrylate (DMAEMA), dimethylaminoethyl acrylate (DMAEA), acrylic acid (AAc), polyethylene glycol (PEG) and methacrylic acid (MAAc).” [emphasis added]([0014])(instant claim 10). SUNG teaches that: “The hydrogel functional layer may further include a crosslinking agent. The hydrogel functional layer may include 55 to 98% of the main monomer, 2 to 40% of the comonomers and 0.1 to 5% of the crosslinking agent.” ([0015]). And particularly that: “For example, desirably, the main monomer may be N-isopropylacrylamide (a temperature-sensitive hydrogel), and the comonomer may be acrylic acid (a pH-sensitive hydrogel). In this example, a crosslinking agent may be N,N'-methylene-bis-acrylamide (BIS).” ([0084]), and further “For example, the hydrogel functional layer may include 55 to 98% of N-isopropylacrylamide, 2 to 40% of acrylic acid, and 0.1 to 5% of a BIS crosslinking agent.” ([0086])(instant claims 11-15).
Finding of prima facie obviousness
Rationale and Motivation (MPEP 2142-2143)
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to produce a biocompatible hydrogel complex capable of binding to, activating, and expanding immune cell, e.g., T-cells, as suggested by KEVLAHAN, the hydrogel being a soft-deformable microgel composed of poly(N-isopropylacrylamide) and acrylic acid, as suggested by Bachman et al. and SUNG as suitable hydrogels for protein binding in therapeutic, diagnostic and drug delivery applications.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention as it would have required no more than an ordinary level of skill in the art to produce a deformable hydrogel per the teachings of KEVLAHAN, Bachman et al., SUNG and the ordinary level of skill in the art to which the invention pertains. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a).
Claims 19 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over KEVLAHAN in view of Bachman et al. and SUNG as applied to claims 1-8, 11-13 and 22 above, and further in view of ROTH (US 2019/0240154; published August, 2019).
Applicants Claims
Applicant claims a hydrogel particle being deformable and having at least one protein, which is capable of binding to a cell surface component of cancer cells or T-cells, bound to the surface of the hydrogel particle (instant claim 1).
Determination of the scope
and content of the prior art (MPEP 2141.01)
The disclosure/teachings of KEVLAHAN is discussed above and incorporated herein by reference.
The teachings of Bachman et al. are discussed above and incorporated herein by reference.
The teachings of SUNG are discussed above and incorporated herein by reference.
Ascertainment of the difference between
the prior art and the claims (MPEP 2141.02)
The difference between the rejected claims and the teachings of KEVLAHAN is that KEVLAHAN does not expressly teach a pharmaceutical composition for treating cancer or an immuno-oncology agent comprising the hydrogel particle of claim 1.
ROTH teaches that: “Systemic biologic therapy using protein-based reagents such as antibodies, cytokines, chemokines and growth factors has become clinically viable and many FDA-approved applications have already reached the market. The majority of these are related to cancer immunotherapy and to the treatment of autoimmune disease. However, these therapies usually require the infusion of a large quantity of the given protein reagent in order to achieve adequate systemic exposure and/or to overcome short biologic half-lives. As a result, the cost required to generate systemic doses of these reagents can be prohibitive and side effects/toxicity are common and can be both debilitating and limiting.” ([0004]). And “For example, recent advances in immunotherapy targeting checkpoint inhibitors such as PD-1 and CTLA-4 are revolutionizing cancer therapy and out-performing conventional chemotherapy for melanoma, lung cancer, and other tumors […].” ([0005]). And “To reduce the costs, side effects, and toxicity, research is being done to find methods and apparatuses to control release of protein-based reagents.” ([0006]). And further that: “hydrogels can persist for weeks to months as a solid mass, ultimately limiting the capacity for repeated injections at the same site or producing unwanted cosmetic or functional consequences due to mass effects that last beyond the time required for the intended therapy. In addition, if an added reagent is bound to the hydrogel and the hydrogel persists without degradation, the added reagents may be trapped and retained within the hydrogel for an extended period beyond their intended therapeutic window, yet released at some delayed time-point that is not appropriate for the intended use.” ([0009]).
ROTH teaches that: “In some instances, the therapeutic antibody targeting an immune check point inhibitor is an anti CTLA-4 antibody, anti PD-1 antibody, and/or anti PD-Ll antibody. It is contemplated that any of these may be specifically excluded in an embodiment. The hyaluronic acid-based hydrogel or composition disclosed herein can contain multiple immune check point inhibitor antibodies, such as, but not limited an anti CTLA-4 antibody and an anti PD-1 antibody.” ([0027]). And that: “In some aspects, disclosed herein is a method for treating a subject by administering to the subject any one of the hyaluronic acid-based hydrogel or composition disclosed herein containing one or more biologically active agent(s). The method can be for treating a cancer in a subject. […] In some embodiments, the method further comprises administering a second biologically active agent(s) that is different than the biologically active agent contained in the hydrogel or composition disclosed herein. The second biologically active agent can be encapsulated in a second hyaluronic acid-based hydrogel or composition disclosed herein. In some embodiments, the second biologically active agent is not encapsulated in a hyaluronic acid-based hydrogel or composition disclosed herein. In some embodiments, the method further comprises administering the hyaluronic acid-based hydrogel or composition disclosed herein with a second therapy.” ([0029]).
Finding of prima facie obviousness
Rationale and Motivation (MPEP 2142-2143)
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to produce a biocompatible hydrogel complex capable of binding to, activating, and expanding immune cell, e.g., T-cells, as suggested by KEVLAHAN, the hydrogel being a soft-deformable microgel composed of poly(N-isopropylacrylamide) and acrylic acid, as suggested by Bachman et al. and SUNG as suitable hydrogels for protein binding in therapeutic, diagnostic and drug delivery applications, and particularly as a pharmaceutical composition/immuno-oncology agent for the treatment of cancer in a human subject, as suggested by ROTH.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention as it would have required no more than an ordinary level of skill in the art to produce a deformable hydrogel per the teachings of KEVLAHAN, Bachman et al., SUNG, ROTH and the ordinary level of skill in the art to which the invention pertains. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a).
Response to Arguments:
Applicant's arguments filed 11/11/2025 have been fully considered but they are not persuasive.
Applicant’s argument regarding the intended use as a deformable immuno-oncology agent (p. 5, paragraphs 3-5), and particularly that: “The present inventors have developed hydrogel-based, deformable immuno-oncology agent particles that act like artificial T-cells, which can prevent the immune system evasion mechanism of cancer cells by binding to cancer cells and/or T-cells to block the interaction between them. The hydrogel has an appropriate softness and/or (visco) elastic modulus to be deformable at the cell surface. The hydrogel according to the present disclosure is soft, that is, has high ductility. In one aspect of the subject invention that exhibits these properties, the elastic modulus of the hydrogel particles at 25°C may be in the range of 0.01 Pa to 100 Pa […].” (paragraph bridging pp. 5-6).
In response to applicant's argument that “hydrogel-based, deformable immuno-oncology agent particles that act like artificial T-cells”, a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.
Applicant further argues that: “In the context of the present invention, the term "deformable'' means that the physical shape of a hydrogel particle can spontaneously change due to its softness when the hydrogel comes into contact with a cell. In particular, this means that when it comes into contact with other cells, the hydrogel, which had a spherical shape in body fluid, stretches thinly and widely without being broken or destroyed to have a formation that covers the cells. The definition recited in amended Claim l numerically expresses such a property.” (p. 6, 2nd paragraph).
In response the examiner argues that one of ordinary skill would have recognized that a hydrogel such as a poly(N-isopropylacrylamide-co-(meth)acrylic acid) copolymer is produced by crosslinking and the prior art clearly suggest ultrasoft (deformable) hydrogels formed by a low degree of crosslinking (Bachman et al. suggesting “The resulting particles have extremely low (<0.5%), core-localized crosslinking resulting from rare chain transfer reactions.” – Abstract, lines 7-8). Therefore, it would have been prima facie obvious to optimize the amount of crosslinking to produce hydrogel particles that: “Due to their softness and deformability, ULC microgels are a unique base material for a wide variety of biomedical applications including biomaterials for drug delivery and regenerative medicine.” (Bachman et al., last three lines of abstract).
Applicant argues that: “Kavalhan describes methods and compositions for modulation of immune cells, including a biocompatible hydrogel complex capable of binding to, activating, and expanding immune cells. such as T-cells (page 2, lines 13-19) . Kavlahan indicates that the structure may have any suitable shape, and it is preferable for the complex to have a high surface area ratio to maximize available surfaces (page 19, lines 5-8). Elongated shapes, such as wire and tubular shapes as well as spherical shaped particles, are possible (page 19, lines 9-14). The elastic modulus of the polymer of Kavlahan may range from 0.8 GPa ([…]) to 0.0001 GPa ([…]) (page 5, lines 25-30). The hydrogel is not described as "deformable".” (p. 6, 4th paragraph).
In response the examiner argues that KEVLAHAN teaches that: “The hydrogel complex can have an elastic modulus of less than 100,000 Pa. In some embodiments, the binding moiety binds to a cell surface component of a T cell.” (p. 9, lines 12-14, also see [0118] & [0119] discussing the elastic modulus of alginic-acid-based polymeric moiety). MPEP §2144.05(I) - In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. “an elastic modulus of less than 100,000 Pa” overlaps with “an elastic modulus at 25 °C in the range of 0.01 Pa to 100 Pa.” (instant claim 22). KEVLAHAN more narrowly teaches that: “An elastic modulus of a hydrogel, e.g., that is suitable to allow a population of T cells to retain one or more characteristics of a naive phenotype, may be between 100 pascals (Pa) and 100,000,000 Pa (e.g., from 100 Pa to 1,000 Pa,” (p. 17, lines 26-28), which is clearly within the scope of Applicants definition of deformable as instant claim encompasses close to 100 Pa which is disclosed by KEVLAHAN (MPEP 2144.05-I – “Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close.”
Applicant further argues that Bachman et al is an article describing ultrasoft, highly deformable microgels. The microgels are "soft relative to crosslinked microgels, with a Young's modulus of ~10 Kpa” (abstract). There is no suggestion that the microgels are so soft and deformable that they would spontaneously change due to its softness when the hydrogel comes into contact with a cell, such that [it] would cover cells.” (paragraph bridging pp. 6-7).
In response the examiner argues that one of ordinary skill would have recognized that a hydrogel such as a poly(N-isopropylacrylamide-co-(meth)acrylic acid) copolymer is produced by crosslinking and the prior art clearly suggest ultrasoft (deformable) hydrogels formed by a low degree of crosslinking (Bachman et al. suggesting “The resulting particles have extremely low (<0.5%), core-localized crosslinking resulting from rare chain transfer reactions.” – Abstract, lines 7-8). And KEVLAHAN teaches microgels having an elastic modulus of less than 100,000 Pa (broad) and from 100 Pa to 1,000 Pa (narrow). Clearly suggesting that the ultrasoft and deformable microgel (hydrogel particles) have utility such as biomaterials for drug delivery. “Due to their softness and deformability, ULC microgels are a unique base material for a wide variety of biomedical applications including biomaterials for drug delivery and regenerative medicine.” (Bachman et al., last three lines of abstract).
Applicant argues that: “Sung and Roth have been cited for elements of dependent claims. The definition of "deformable" has been incorporated into the claims: "deformable" means that the diameter (D) of the height axis of the hydrogel particle decreases by 30 to 99% in a state in which the hydrogel contacts the cell and covers the cell, compared with the diameter of the height axis of the hydrogel in a spherical state before the hydrogel particle contacts the cell. As noted in the present application, in one aspect of the subject invention that exhibits these properties, the elastic modulus of the hydrogel particles at 25 °C may be in the range of 0.0·1 Pa to 100 Pa. Neither Kavlahan nor Bachman et al. suggest an elastic modulus less than 100,000 Pa, more than a 1000-fold difference. Kavlahan does not suggest hydrogels or polymers which are so soft that they would decreases in diameter (D) of the height axis of the hydrogel particle by 30 to 99%, when the hydrogel contacts a cell. In fact, Kavlahan describes shapes of the particles, so the hydrogel complex cannot be so soft as to spontaneously form spheres at room temperature, and furthermore Kavlahan prefers shapes having high surface area ratios to maximize available surfaces, teaching against a level of malleability so high as to not retain a high surface area, Applicant submits that the claimed invention is neither anticipated by, nor obvious over, the applied references, withdrawal of these grounds of rejection ls respectfully requested.” (p. 7, 2nd paragraph).
In response the examiner argues that one of ordinary skill would have recognized that a hydrogel such as a poly(N-isopropylacrylamide-co-(meth)acrylic acid) copolymer is produced by crosslinking and the prior art clearly suggest ultrasoft (deformable) hydrogels formed by a low degree of crosslinking (Bachman et al. suggesting “The resulting particles have extremely low (<0.5%), core-localized crosslinking resulting from rare chain transfer reactions.” – Abstract, lines 7-8). And KEVLAHAN teaches microgels having an elastic modulus of less than 100,000 Pa (broad) and from 100 Pa to 1,000 Pa (narrow). Clearly suggesting that the ultrasoft and deformable microgel (hydrogel particles) have utility such as biomaterials for drug delivery. “Due to their softness and deformability, ULC microgels are a unique base material for a wide variety of biomedical applications including biomaterials for drug delivery and regenerative medicine.” (Bachman et al., last three lines of abstract).
Conclusion
Claims 1-8, 11-13, 19-20 and 22 are pending and have been examined on the merits. Claim 7-8 and 13 is rejected under 35 U.S.C. 112(b); claims 1-8, 11-13, 19-20 and 22 are rejected under 35 U.S.C. 103. No claims allowed at this time.
Applicant's amendment necessitated the new 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.
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/IVAN A GREENE/Examiner, Art Unit 1619
/TIGABU KASSA/Primary Examiner, Art Unit 1619
1 Of record as cited by the Examiner in the Requirement for Restriction/Election dated 05/29/2025.
Prosecution Insights