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 .
Election/Restrictions
Claims 18-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected inventive group, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 10/31/2025.
Applicant's election with traverse of inventive group I in the reply filed on 10/31/2025 is acknowledged. The traversal is on the ground(s) that the product of inventive groups I-IV serves as the linking feature common to all claims. This is not found persuasive because as set forth previously, the claimed product can be used in each of the three methods presented and additionally has other uses such as cell culture, drug testing in vivo or in vitro, or for tissue regeneration and engineering. As such, this renders each inventive group patentably distinct. Therefore the argument is not found persuasive, and the restriction is maintained.
The requirement is still deemed proper and is therefore made FINAL.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
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 (i.e., changing from AIA to pre-AIA ) 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.
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, 6, and 10-16 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (US 2019/0091367 A1) in view of Eisenfrats et al. (US 2018/0028715 A1)
Regarding claims 1 and 4: Li et al. teaches a biocompatible adhesive hydrogel system comprising a first and second polymer network (57) wherein the first polymer network and second polymer network are crosslinked together. (0072) Furthermore, Li teaches that the hydrogel may be used as an injectable. (0071) Li fails to teach a specific pore size for the hydrogel of the claimed invention.
Eisenfrats et al. teaches an occlusive device to be used via injection which may be used in sterilization. (57) Eisenfrats teaches that the device is to be a hydrogel or form a hydrogel in situ upon administration (0011) and that the pore size of the hydrogel may be less than 3 microns to prevent the flowthrough of cells. (0074) However, Eisenfrats further teaches that the hydrogel may be semi-permeable, allowing certain fluids and material to flow through while inhibiting others. (0054) In addition to this, Eisenfrats teaches that the porosity may be tailored and among the embodiments, the pore diameter of the formed polymer can range from 0.001nM to 3uM (0094), reading on claim 4. One skilled in the art would be motivated by this teaching to combine the porosity size as taught by Eisenfrats (under 3uM) with the polymer network composite taught by Li to create a semi-permeable composite hydrogel which is injectable and has a pore size of at least 1uM. A person skilled in the art would have had motivation and a reasonable expectation of success at doing so due to Eisenfrats teaching that use of semi-permeability results in the ability to control what fluids or objects are allowed to pass through the hydrogel.
Regarding claims 2 and 3: Li teaches an example of the invention (Example 2) in which a hydrogel was created using high density materials (such as chitosan, gelatin, and polyethylene) were dissolved into a MES buffer at a weight of 2.0%. This reads on both claims 2 and 3 of the first and second polymers having a weight to volume ratio of 0.25-4% (claim 2, the first polymer) and 0.15-8% (claim 3, the second polymer). (0112)
Regarding claim 6: Li teaches that the hydrogel should have an interfacial fracture toughness of about 100 J/m2 to about 5000 J/m2. *0091) This reads on having a fracture toughness of at least 5 J/m2.
Regarding claims 10 and 12: Li teaches that the first polymer network is selected from a group of polymers including poly(N-isopropylacrylamide). (0009) Furthermore, regarding claim 10, it is known in the art that the pKa of poly(N-isopropylacrylamide) is about 6 which is evidenced by the Specification submitted by the Applicant in paragraph 0184. Therefore, use of poly(N-isopropylacrylamide) as taught by Li further satisfies the requirement of claim 10 regarding the requirement of the first polymer having a pKa of 6-6.5.
Regarding claims 11 and 14: Li teaches crosslinking, but either covalent or ionic crosslinking which fails to read on use of self-crosslinking. Eisenfrats teaches cross-linking of the polymer used in the hydrogel and gives the example of carbon by way of carbon-based crosslinking which bind directly to the carbon allotrope. (0062) A person of ordinary skill in the art would be motivated to incorporate this teaching into the hydrogel taught by Li due to not requiring an additional chemical cross-linking step in the hydrogel formation process, which would be necessary if covalent or ionic crosslinking was used. One skilled in the art would have motivation and a reasonable expectation of success based due to the fact that self-crosslinking negates the need for further chemical cross-linking steps.
Regarding claim 13: While Li teaches the primary embodiment of the invention to have the second polymer be ionically crosslinked (0006), Li does specify an additional embodiment of the invention in which both the first and second polymers are covalently coupled. (0011)
Regarding claims 15 and 16: Li et al. fails to teach use of enzymatic crosslinking via peptide bonds for the second polymer of the hydrogel composition. Eisenfrats et al. teaches that the device (hydrogel) of the claimed invention may be cross-linked with peptides such as polyethylene glycol, which has the potential to enhance the biocompatibility of the device. (0071) A person skilled in the art would have been motivated to incorporate the teaching of Eisenfrats of use of polyethylene glycol as a crosslinking peptide into the hydrogel as taught by Li and had reason to do so and a reasonable expectation of success due to the teaching of Eisenfrats that use of polyethylene glycol as a crosslinking agent can enhance the biocompatibility of the composition.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (US 2019/0091367 A1) in view of Eisenfrats et al. (US 2018/0028715 A1) and Tokatlian et al. (Porous Hyaluronic Acid Hydrogels for Localized non-Viral DNA Delivery in a Diabetic Wound Healing Model, 2015)
The teachings of Li and Eisenfrats are disclosed above. Both fail to teach use of a hydrogel with a porosity percentage specifically between 18-70%.
Regarding claim 5: Tokatlian et al. teaches the use of porous vs. non-porous hydrogels when used in wound recovery to promote angiogenesis wherein the hydrogels had been impregnated with pro-angiogenic factors. (Pg 1, Abstract) It was found that when used in wound closure, the porous hydrogels with a porosity of 45-65% allowed for faster cell infiltration which corresponded to higher levels of early angiogenesis when compared with non-porous (n-pore) hydrogels. (Pg 5, 2.3) This reads on use of a hydrogel with a porosity between 18-70%.
It would have been obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teaching of use of a hydrogel with a porosity between 45-65% with the hydrogel of Li. A person skilled in the art would have had motivation and a reasonable expectation of success based on the teachings of Tokatlian, who state that when compared with n-pore hydrogels, the hydrogels with a porosity of between 45-65% allowed for faster infiltration of cells, resulting in earlier angiogenesis formation.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (US 2019/0091367 A1) in view of Eisenfrats et al. (US 2018/0028715 A1) and Soltanahmadi et al. (Fabrication of Cartilage-Inspired Hydrogel/Entangled Polymer-Elastomer Structures Possessing Poro-Elastic Properties, 2021)
The teachings of Li and Eisenfrats are discussed above. Both fail to teach use of a hydrogel with a permeability of between 10-14 to 10-12 m2.
Regarding claim 7: Soltanahmadi teaches hydrogels which have been engineered to replicate the load-bearing properties of articular cartilage. (Pg 2694, Abstract) Specifically, Soltanahmadi states that for materials with high permeability coefficients of greater than 10^12 m/s, fluid exudation occurs within fractions of a second. (Pg 2701, Results and Discussion) This reads on use of a hydrogel with a permeability of 10^14 to 10^12m/2. A person skilled in the art would understand that high permeability is required for biocompatible materials placed within the body, as the body is an aqueous environment. Soltanahmadi further states that current conventional hydrogels comprise poor mechanical characteristics such as their compressive behavior which limit their load-bearing applications and that ultrafast recovery behavior and water swelling restraint is useful as it is inspired by cartilage. (Pg 2694, Abstract)
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the teaching of Soltanahmadi of a high permeability rate with the hydrogel of Li. A person skilled in the art would have had motivation and a reasonable expectation of success based on the teachings of Soltanahmadi due to the teaching that high permeability of over 10^12m/s result in fluid exudation within fractions of a second, thereby mimicking cartilage.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (US 2019/0091367 A1) in view of Eisenfrats et al. (US 2018/0028715 A1) and Kalow et al. (WO 2019/222635 A1)
The teachings of Li and Eisenfrats are discussed above. Both fail to teach use of a half-life stress relaxation time from 10 to 100 seconds.
Regarding claim 8: Kalow teaches reversibly photo-crosslinkable hydrogel networks and methods for using said hydrogels in cell culture and tissue engineering applications. (0005) Kalow further teaches that the hydrogels of the claimed invention can be tunable, and may have viscoelastic properties by displaying stress relaxation with a half-life under 100 seconds. (0041) This reads on having a half-life time of stress relaxation from 10 to 100 seconds. Furthermore, Kalow teaches that the ability to tune viscoelastic properties is significant for tissue engineering due to the nuanced differences in cellular microenvironments which impact cellular migration, proliferation, differentiation, and organ function. (0043)
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teaching of Kalow of use of viscoelastic properties within a hydrogel to the hydrogel as taught by Li. A person skilled in the art would have had motivation and a reasonable expectation of success based on the teachings of Kalow of viscoelastic properties allowing hydrogels to be fine-tuned to be suitable for different cell microenvironments, impacting cell and even whole organ function.
Claims 9 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (US 2019/0091367 A1) in view of Eisenfrats et al. (US 2018/0028715 A1), Liu (A functional chitosan-based hydrogel as a wound dressing and drug delivery system in the treatment of wound healing, 2018) and Hu et al. (Visible light crosslinkable chitosan hydrogels for tissue engineering, 2012)
The teachings of Li and Eisenfrats are discussed above. Both Li and Eisenfrats fail to teach use of glycol-chitosan, polyacrylamide, collagen, fibrin, polyethylene glycol, or gelatin as the second polymer and that the double network hydrogel has a fractocohesive length of 0.25-0.5mm.
Regarding claim 9: Liu teaches the generation of functional active wound dressings composed of chitosan, which is known in the art for being biodegradable, biocompatible, antimicrobial, biologically adhesive, and non-toxic, making it an ideal choice for in vivo use of hydrogels. (Pg 7533, Abstract) It is known in the art that the fractocohesive length of chitosan is around 0.5mm. Therefore, a person skilled in the art would be motivated to select chitosan for the first polymer of the hydrogel composition, as it is considered ideal for wound healing (pg 7533, Abstract) and is an ideal hydrogel material. Liu fails to teach use of glycol-chitosan.
Hu teaches use of in situ gelling constructs which form a hydrogel at the site of injection, allowing delivery of cells and growth factors to the site of a wound for use in tissue engineering. The hydrogels of the claimed invention are that of methacrylated glycol chitosan. (Pg 1730, Abstract) Hu further teaches that glycol chitosan is a water-soluble chitosan derivative which increases the solubility of the material when compared to straight chitosan and that this increased solubility makes the material favorable for direct cell encapsulation within the gels. (Pg 1730, Introduction) This would make glycol chitosan an ideal choice for the second polymer of the composition, and give motivation to a person of ordinary skill in the art to utilize the material. It is known in the art that the fractocohesive length of glycol chitosan is up to 0.5mm.
Therefore, a composition made from the two polymers chitosan (as is one of the options for the first polymer as required by claim 12) and glycol chitosan (as is one of the options for the second polymer as required by claim 17) would inherently have a fractocohesive length of 0.25-0.5mm in length, as both polymers used in the composition comprise fractocohesive lengths of about 0.5mm.
Regarding claim 17: Following the discussion of claim 9 above, Hu states use of glycol chitosan and its benefits regarding cell encapsulation and usefulness for gelling in situ, making it an ideal choice for the second polymer. This reads on use of glycol-chitosan as the second polymer of the double network hydrogel.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Liu and Hu of use of chitosan and glycol-chitosan for the first and second polymers of the hydrogel composition as taught by Li. One skilled in the art would have been motivated and had a reasonable expectation of success at doing so based on the teachings of Liu who state that chitosan based hydrogels are biodegradable, biocompatible, non-toxic, antimicrobial, and biologically adhesive, and the teachings of Hu who state that use of glycol-chitosan increases the solubility of the composition, making it ideal for in situ gelling and cell encapsulation.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HANNA M THUESON whose telephone number is (571) 272-3680. The examiner can normally be reached M-F 7:30-5 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.
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/HANNA MARIE THUESON/ Examiner, Art Unit 1638
/CHRISTOPHER M BABIC/ Supervisory Patent Examiner, Art Unit 1633