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 .
The Action mailed 02/05/2026 is vacated in favor of this action. The statutory period for reply has been corrected to “3” months from “2” months from the mailing date.
Claim Interpretation
Applicant discloses use of a “body enzyme” for the oxidation of the functionalized phenol derivative. The Specification as provided by the Applicant fails to clearly define what constitutes a “body enzyme”, simply stating that “the oxidation may be carried out by a body enzyme without addition of an oxidizer or enzyme” (0072). Therefore, “body enzyme” shall be interpreted as any enzyme that can be found in the body. As such, hydrogels functionalized with any enzyme that naturally occurs in the body will read on the claimed method.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 7 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. The term “body enzyme” is not clearly defined in either the specification or claimset provided by the Applicant.
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.
Claim(s) 1-4, 8, and 10-24 are rejected under 35 U.S.C. 103 as being unpatentable over Haneda et. al (US 2020/0407672 A1) in view of Hwang et. al (US 2020/0362208 A1) and Martin et al. (US 2020/0069846 A1)
Regarding claims 1, 3, 4 and 24: Haneda teaches scaffolding materials for cell culture. (57) Specifically, the hydrogel comprises a polyalcohol which may be catechol. (0158) This functions as a cross-linking agent and reads on the claim regarding a hydrogel functionalized with a phenol derivative. Haneda fails to teach use of a decellularized tissue-derived extracellular matrix for the source of the hydrogel.
Martin teaches a method for healing a soft tissue defect with composite materials including a gel. (57) Martin further teaches that the decellularized extracellular matrix (hereafter ECM) of adipose tissue is of particular interest due to its porous and highly fibrous nature. (0093) Combined with the teachings of Haneda disclosed above, this reads on both claim 1 and claim 24. Due to this, a person of ordinary skill in the art would have been motivated to use the porous and fibrous decellularized adipose ECM along with the scaffolding materials comprising catechol to create a hydrogel which includes a decellularized tissue-derived ECM functionalized with a phenol derivative. This further reads on the teachings of claim 3 of use of a tissue including fat tissue and claim 4 regarding decellularization of said tissue.
Regarding claim 2: Haneda teaches use of a polyalcohol which includes catechol (a phenol derivative) and pyrogallol (a pyrogallol group), reading on use of a phenol derivative and pyrogallol group incorporated into the hydrogel.
Regarding claim 8: Haneda teaches that the scaffolding material for cell culture may be used in a state closer to an in-vivo like state, such as a porous membrane or hydrogel. (0147) In addition to this, Martin teaches that use of adipose ECM is favorable for scaffolding materials due to its porous nature.
Regarding claim 10: Haneda fails to teach use of a material which has an adhesive property. Hwang teaches an adhesive composition comprising a polyvinyl alcohol, water-soluble polyphenol compound, and water. (0009) Specifically, Hwang teaches an adhesive composition which can adhere without a curing process and be used as a medical adhesive, adhesive patch, drug delivery adhesive, or moist wound healing dressing. (030-0031) The property of adhesiveness is advantageous as an embodiment of the invention is one of a controlled drug delivery setting. (0078)
Regarding claim 11: Haneda fails to teach use of a biodegradable material. Hwang teaches use of a PVA polymer which is biodegradable, water soluble, and able to be broken down by bacteria found in soil, making it excellent for sensitive use in the protection of the environment. (0042) Due to the environmental benefits of being biodegradable, a person of ordinary skill in the art would have been motivated to incorporate the teachings of Hwang of use of a biodegradable material with the teachings of Haneda.
Regarding claim 12: Haneda teaches a scaffolding material to be used in cell culture. (57)
Regarding claim 13: Haneda teaches an embodiment of the invention which uses the scaffolding material in a three-dimensional culture method comprising a hydrogel. (0147) In addition to this, Martin teaches use of a “gel” which is defined as a “solid three-dimensional network”. (0064)
Regarding claim 14: Haneda fails to teach use of a composition promoting differentiation. Martin teaches a composite hydrogel comprising adipose ECM which has been fragmented and mixed with hydrogel precursor solutions. (0093) This composite solution allows stronger mechanical reinforcement from the solid ECM fiber component and allows for independent tuning of the hydrogel regarding porosity. The fibers further function as guides for adipose stem cells, supporting cell migration and differentiation and therefore being a preferred cell adhesion substrate. (0094) This would give a person of ordinary skill in the art motivation to incorporate the use of adipose ECM fibers into the composition taught by Haneda as the fibers act to support stem cell differentiation.
Regarding claim 15: Haneda teaches that the composition of the invention may be used in the culture of stem cells. (0141)
Regarding claim 16: Haneda teaches that the composition of the invention may be used in the culture of iPS cells and embryonic germ stem cells. (0143)
Regarding claim 17: Haneda fails to teach use of the composition in a drug delivery setting. Hwang teaches that the adhesive composition may be applied as a medical adhesive, including a drug delivery adhesive. (0031) A person skilled in the art would recognize that the adhesive property is what allows for the ability of the invention to be used as a controlled drug delivery system (0025), giving one motivation to include the adhesive property of the material into the invention as claimed by Haneda.
Regarding claims 18 and 19: Following the discussion of claim 17 above, use of the adhesive as a controlled drug delivery adhesive further satisfies claim 18, as Hwang states that the composition may contain a therapeutic drug for the purpose of delivery. (0078) Hwang goes on to list examples of therapeutic agents for use in the composition, including antibodies and peptides (0078), which reads on claim 19.
Regarding claims 20 and 23: Haneda teaches that the scaffolding material for cell culture is preferably used in the form of a film. (0144) This reads on both the teachings of claim 20 and claim 23.
Regarding claim 21: Haneda fails to teach a composition for promoting tissue regeneration. Hwang teaches that the composition of the disclosed invention may be used as a moist wound healing dressing which comprises antimicrobial properties; this functions to alleviate pain, shorten the treatment period, minimize scarring, and increase the rate of growth for epithelial cells by providing a wet environment. (0076) In addition, Martin teaches that the composition of the claimed invention is particularly useful in soft tissue regeneration (0239) and may comprise epidermal growth factor (a tissue repairing agent, 0172), heparin to promote angiogenesis and facilitate soft tissue repair (0145), and hyaluronic acid which is a potent regulator of endothelial cell regeneration (0124). A person skilled in the art would be motivated to incorporate the teachings of Hwang and Martin of an adhesive moist wound healing dressing that can additionally contain components which aid in soft tissue regeneration in the composition of Haneda based on the above discussion.
Regarding claim 22: Haneda fails to teach use of the composition of the invention for tissue implantation. Martin teaches an embodiment of the invention in which a scaffold complex (such as a polymeric fiber and hydrogel material) can be implanted into a subject where the scaffold complex promotes tissue growth and cell infiltration. (0063) Furthermore, as discussed above, Martin details compositions which may comprise additives to facilitate tissue regeneration such as heparin, epidermal growth factor, and hyaluronic acid. One skilled in the art would be motivated to incorporate the teachings of Martin of an implantable scaffold which may contain agents which aid in tissue regeneration with the composition of Haneda due to the regenerative properties of the scaffold taught by Martin.
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 Haneda of a hydrogel comprising a phenol derivative and pyrogallol group with the teachings of Hwang specifying use of the hydrogel in a drug delivery as a film and the teachings of Martin of use of decellularized adipose ECM to create a hydrogel composition suitable for drug delivery comprising decellularized ECM which facilitates the culture and differentiation of stem cells. A person skilled in the art would have had motivation and a reasonable expectation of success based on the following reasons:
Hwang teaches that adhesive compositions are useful as medical adhesives, drug delivery adhesives, and moist wound dressings which speed up the rate of growth for epithelial cells. Hwang further teaches use of a biodegradable hydrogel, which is beneficial for the environment.
Martin teaches that incorporation of decellularized adipose ECM functions as a guide for adipose stem cells, supporting cell migration and differentiation due to its porous and highly fibrous nature.
Based on the discussion above, claims 1-4, 8, and 10-24 are rendered obvious.
Claims 5-7 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Haneda et. al (US 2020/0407672 A1) in view of Hwang et. al (US 2020/0362208 A1), Martin et al. (US 2020/0069846 A1), and Texeira et al. (Enzyme-catalyzed crosslinkable hydrogels: Emerging strategies for tissue engineering, 2012)
The teachings of Haneda, Hwang, and Martin are discussed above. All fail to teach use of a body enzyme or oxidation of the functionalized phenol derivative via addition of an oxidizer or enzyme.
Regarding claims 5 and 7: Teixeira teaches an overview of the development of crosslinkable hydrogels for tissue engineering which are able to be easily and efficiently formed by enzyme-catalyzed reactions in situ. (Pg 1281, Abstract) Specifically, Teixeira teaches that tyrosinases catalyze the oxidation of phenols into activated quinones, which can react with a hydroxyl group or amino acid. Tyrosinases are also present in both plants and animals. Furthermore, hydrogels catalyzed by tyrosinases require some sort of fiber such as chitosan (alternatively, the adipose ECM taught by Martin) in order to gel and form mechanically weaker hydrogels. However, this weakness to the gel makes hydrogels catalyzed by tyrosinase excellent for applications such as wound dressings. (Pg 1283-1284, 2.2) This reads on the preparation of the hydrogel via oxidation of the functionalized phenol derivative. A visualization of the reaction is pictured below:
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As tyrosinase is found in the body, this further reads on claim 7 regarding the oxidation being carried out by a body enzyme and since, per the diagram pictured above no co-factors are needed, reads on claim 7 regarding the reaction taking place without the addition of an oxidizer or enzyme.
Regarding claims 6 and 25: As tyrosinase is both an enzyme and one that functions via oxidation of the phenol group, this reads on both the addition of an oxidizer or an enzyme as required by claim 6 and a process of oxidizing the functionalized phenol derivative, as is required by claim 25.
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 Hwang, Haneda, and Martin with the teachings of Teixeria to form a hydrogel comprising a decellularized tissue-derived extracellular matrix which is functionalized with a phenol derivative. One of ordinary skill in the art would have been motivated to do so based on the teachings of Teixeria, who state that tyrosinase, an enzyme found in the body, reacts by oxidizing phenols, resulting in a soft hydrogel useful for applications such as a wound dressing.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Haneda et. al (US 2020/0407672 A1) in view of Hwang et. al (US 2020/0362208 A1), Martin et al. (US 2020/0069846 A1), and Raia et al. (US 20190282731 A1)
The teachings of Haneda, Hwang, and Martin are discussed above. All fail to disclose use of a hydrogel with an elastic modulus from 100Pa to 1500Pa at 1Hz.
Regarding claim 9: Raia teaches compositions including silk fibroin and a phenol-containing polymer, resulting in a crosslinked composition. (57) Specifically, said compositions are suitable for implantation and administration to a subject, (0016) and are provided at a range of 200Pa and 500kPa (0018) at 1Hz (0174). Example 10 of the claimed invention teaches a composition of silk hydrogels, one with a storage moduli of 0.55 +/- 0.03 kPa, which reads on the range of claim 9 of 100Pa-1500Pa. (0216) These compositions, in some embodiments, are also biodegradable. (0010)
It would have been obvious to a person of ordinary skill in the art to combine the teachings of Haneda, Hwang, and Martin with the teachings of Raia to create a hydrogel composition with an elastic modulus of 100Ph to 1500Pa at 1Hz. A person skilled in the art would have had motivation and a reasonable expectation of success based on the teachings of Raia, who state that the disclosed compositions, of which the silk hydrogel of example 10 is one, are suitable for implantation and administration to a subject in addition to being biodegradable.
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
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638