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
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119
(a)-(d). Acknowledgment is made of Applicants’ claim for benefit to foreign application GB2017052.8 filed 10/27/2020.
This application claims the benefit of priority to Patent Application PCT/EP2021/079887. Acknowledgement is made of Applicants’ claim for benefit to prior filed to Patent Application Number PCT/EP2021/079887, filed on 10/27/2020.
Information Disclosure Statement
The IDS filed 04/27/2023 has been considered by the Examiner.
Status of Claims
Claims 1-22 are under examination.
Claim Rejections - 35 USC § 102
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 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, 5, 7-9, 12, and 14-22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lim et al. (WO2019/180423 A1).
Regarding claim 1, Lim et al. teach a method of preparing a porous protein scaffold for supporting the growth of biological tissue (cover page, abstract). (a) Lim et al. teach the protein is a gellable protein selected from at least one of collagen, fibrinogen, fibronectin, laminin and elastin (page 9, paragraphs 0070 and 0071). Lim et al. teach the method comprises: (b) providing an oil-in water emulsion comprising oil droplets dispersed in a continuous phase comprising a pH-buffered (a) aqueous protein solution (cover page, abstract). (c) Lim et al. teach gelling the protein around the oil droplets, such as by enzymatic activity or by non- enzymatic activity chemical reaction or by thermally controlled gelation (cover page, abstract). (d) Lim et al. teach the emulsion oil droplets may be removed from the scaffold after formation. Lim et al. teach the oil droplets may be removed by elution from the scaffold by washing (page 16, paragraph 00117).
Regarding claim 2, Lim et al. teach the protein is selected from one of (a) collagen, fibrinogen, fibronectin, laminin and elastin (page 61, Claim 2).
Regarding claim 3, Lim et al. teach the protein is fibrinogen (a) (page 61, Claim 2). Lim et al. teach the gelation agent (b) is thrombin (c) (page 8, paragraph 0066).
Regarding claim 5, Lim et al. teach the method of any preceding claim, wherein the oil phase is present in the oil-in water emulsion in an amount in the range of 40 to 75% by volume of the continuous phase (page 62, claim 13). Lim et al. teach the oil phase can be up to 75% (page 62, claim 13) which is a HIPE emulsion. Lim et al. teach surfactant or surfactant mix has the HLB from 11.5 to 15 (page 34, paragraph 00202), which is suitable for high-internal phase emulsions (HIPE). The surfactant can therefore also support 75% oil and has an oil-carrying capacity (OCC) of at least 70%.
Regarding claim 7, Lim et al. teaches crosslinking the protein after the protein has been gelled around the oil droplets and removal of the oil droplets in subsequent steps (page 62, claim 14).
Regarding claim 8, Lim et al. teach scaffold drying and scaffold freeze-drying (page 17, paragraph 00119).
Regarding claim 9, Lim et al. teach a protein-based 3-dimensional tissue scaffold (page 17, paragraph 00123).
Regarding claim 12, Lim et al. teach the scaffold may be incubated with polymers such as polyvinyl alcohol (PVA) (page 16, paragraph 00118).
Regarding claims 14 and 15, Lim et al. teach creation of in vitro tissue-engineered tissues. Lim et al. teach cells are seeded into or onto the scaffold. Lim et al. teach the process in aseptic conditions, in a physiological cell culture medium, and supported in an environment which allows cells to organize on or within the scaffold. Lim et al. teach the process to form a tissue structure or organoid or organ-like structure (page 19, paragraph 00137).
Regarding claim 16, Lim et al. teach scaffolds for tissue engineering purposes. Lim et al. teach the scaffold may be used for engineering heart (page 21, paragraph 00146), often referred to as a myocardial patch. Lim et al. teach the scaffold may also be used for tissue reconstruction of pericardium (page 21, paragraph 00146).
Regarding claim 17, Lim et al. teach a protein-based 3-dimensional tissue scaffold (page 17, paragraph 00123). Lim et al. teach tissue-engineered constructs, tissue equivalents or skin equivalents. Lim et al. teach tissue engineered constructs may be used for implantation as advanced therapy medicinal products (ATMPs), or used for non-clinical investigational purposes, such as drug screening or therapy evaluation (page 19, paragraph 00137).
Regarding claim 18, Lim et al. teach a protein-based 3-dimensional tissue scaffold (page 17, paragraph 00123). Lim et al. teach scaffold use as acellular implants, also referred to as tissue repair scaffolds, to promote histologically organized tissue reconstruction and wound healing (page 19, paragraph 00137).
Regarding claims 19, Lim et al. teach a protein-based 3-dimensional tissue scaffold (page 17, paragraph 00123). Lim et al. teach the scaffolds can be used as an epidermal-dermal bilayer skin substitute (page 50, paragraph 00264).
Regarding claim 20, Lim et al. teach a protein-based 3-dimensional tissue scaffold (page 17, paragraph 00123). Lim et al. teach the scaffolds can be used as an epidermal-dermal bilayer skin substitute (page 50, paragraph 00264). Lim et al. teach the scaffold is useful as both the dermal and epidermal layers can be applied simultaneously (page 50, paragraph 00264).
Regarding claim 21, Lim et al. teach the scaffold is useful for single stage reconstruction of burns and chronic wounds as both the dermal and epidermal layers can be applied simultaneously (page 50, paragraph 00264).
Regarding claim 22, Lim et al. teach the porous protein scaffolds obtained for surgical implantation into a wound site or tissue defect or other site to support the repair or regrowth of the tissue (page 1, paragraph 0001). Lim et al. teach scaffold use as acellular implants, also referred to as tissue repair scaffolds, to promote histologically organized tissue reconstruction and wound healing (page 19, paragraph 00137).
Claims 10 and 11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lim et al. (WO2019/180423 A1) and evidenced by Tamaddon et al. (Journal of Materials Science: Materials in Medicine, 2013).
Regarding claim 10, Lim et al. teach a protein-based 3-dimensional tissue scaffold (page 17, paragraph 00123) with high porosity (page 27 paragraph 00176). High porosity in a protein based scaffold is at least 90% as evidenced by Tamaddon et al. (page 1162, section 3.5 Porosity).
Regarding claim 11, Lim et al. teach fibrin composite scaffolds which include fibrin-chondroitin sulphate, fibrin-hyaluronic acid, and fibrin-gelatin (page 18, paragraph 00131).
Lim et al. teach collagen scaffold stability was achieved (page 26, paragraph 00173).
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 4 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Lim et al. (WO2019/180423 A1) as applied to claim 1 above, and further in view of Gee et al. (US 2008/0027172 A1).
Lim et al. teach a method of preparing a porous protein scaffold for supporting the growth of biological tissue (cover page, abstract). (a) Lim et al. teach the protein is a gellable protein selected from at least one of collagen, fibrinogen, fibronectin, laminin and elastin (page 9, paragraphs 0070 and 0071). Lim et al. teach the method comprises: (b) providing an oil-in water emulsion comprising oil droplets dispersed in a continuous phase comprising a pH-buffered (a) aqueous protein solution (cover page, abstract). (c) Lim et al. teach gelling the protein around the oil droplets, such as by enzymatic activity or by non- enzymatic activity chemical reaction or by thermally controlled gelation (cover page, abstract). (d) Lim et al. teach the emulsion oil droplets may be removed from the scaffold after formation. Lim et al. teach the oil droplets may be removed by elution from the scaffold by washing (page 16, paragraph 00117).
Regarding claims 4 and 6, Lim et al. teach a method for manufacturing a protein-based three-dimensional scaffold. Lim et al. teach the oil-in-water emulsion comprises a non-ionic surfactant (page 2, paragraph 0007). Lim et al. teach the surfactant solution may be prepared from manufactured forms (page 10, paragraph 0083).
Lim et al. do not teach the various non-ionic surfactants to be selected from for the oil-in-water emulsion.
Gee et al. teach within the formulas, R can be the same or a different monovalent hydrocarbon group having 1-18 carbon atoms, or R can be the same or a different organofunctional substituted hydrocarbon group having 1-18 carbon atoms. Gee et al. teach R' represents the hydrogen atom, an alkyl radical containing 1-4 CHC(O)—, carbon atoms, or one of the groups CHCHC(O) , CHOCH2CH2—, or CHOCH2CH2—. Gee et al. teach the preferred R' groups are hydrogen, methyl and ethyl (pages 2-3, paragraphs 0025-0026). Gee et al. teach suitable non-ionic surfactants compositions such as (i) 2.6.8-trimethyl 4-nonyl polyoxyethylene ether sold under the names Tergitol TMN-6 and Tergitol TMN-10 or (ii) the C11-15 secondary alkyl polyoxyethylene ethers sold under the names Tergitol 15-S-7, Tergitol 15-S-9, Tergitol 15-S-15, Tergitol 15-S-30, and Tergitol 15-S-40 (page 4, paragraph 0041).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to have combined the teachings of Lim et al. for a method for manufacturing a protein-based three-dimensional scaffold utilizing a non-ionic surfactant for an oil-in-water emulsion with the teachings of Gee et al. for 2.6.8-trimethyl 4-nonyl polyoxyethylene or C11-15 secondary alkyl polyoxyethylene as non-ionic surfactants for oil-in-water emulsion. Gee et al. provide motivation by teaching that 2.6.8-trimethyl 4-nonyl polyoxyethylene and C11-15 secondary alkyl polyoxyethylene are commercially available surfactants for oil-in water emulsion (page 4, paragraph 0042). Substitution of one known method for another known method, the methods having equivalent effect, is considered to be obvious, absent a showing that the result of the substitution yields more than predictable results. It would have been obvious to one of ordinary skill in the art to utilize one of the non-ionic surfactants taught by Gee et al. as the non-ionic surfactant required by Lim et al. One of skill in the art would have had a reasonable expectation of success at combining Lim et al. and Gee et al. because they both teach non-ionic surfactants for oil-in-water emulsion.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Lim et al. (WO2019/180423 A1) as applied to claims 1 and 9 above, and further in view of Sheoran et al. (Science Direct, 2020)
Lim et al. teach a method of preparing a porous protein scaffold for supporting the growth of biological tissue (cover page, abstract). Lim et al. teach a protein-based 3-dimensional tissue scaffold (page 17, paragraph 00123).
Regarding claim 13, Lim et al. teach generation of in vitro engineered tissues, in which cells are seeded into or onto the scaffold (page 19, paragraph 00137).
Lim et al. do not teach generation of the scaffolds via additive manufacturing.
Sheoran et al. teach Additive Manufacturing (AM) in Bio-Medical for healthcare and pharmaceutical industries because of its ability to fabricate complex customized parts with extensive ease, flexibility and with various biomaterials. Sheoran et al. teach different bio-inks and biomaterials utilized for printing cell-seeded tissues, implants, replacement organ printing and scaffolds. Sheoran et al. teach AM ensures safety, innovation and ease in healthcare sector (page 663, abstract).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to have combined the teachings of Lim et al. for a protein-based 3-dimensional tissue scaffold with the teachings of Sheoran et al. for additive manufacturing of tissues and scaffolds. Sheoran et al. provide motivation by teaching that Bio-printing has been beneficial in printing tissue-like 3D structures that represent anatomical systems for disease modelling, drug testing, and screening. Sheoran et al. teach bio-printing has successfully created basic functional units of anatomical organs known as organoids. Sheoran et al. teach the greatest achievement of bio-printing would be when it fulfils its potential of 3D printing an entirely functioning organ, which can be directly transplanted into a patient’s body (page 669, section 5. Conclusion). One of skill in the art would have had a reasonable expectation of success at combining Lim et al. and Sheoran et al. because both teach generation of in vitro engineered tissues.
Conclusion
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/C.L.M./Examiner, Art Unit 1638
/Anna Skibinsky/
Primary Examiner, AU 1635