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
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) was filed before the mailing date of the non-final first action on the merits. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner. Claim Interpretation
Claims 1-17 are directed to a scaffold comprising a nanocellulose; and a polymer hydrogel. The preamble of claim 1 states that the scaffold is intended for culturing meat ; however, this is considered to be an intended use of the scaffold, not an actual limitation of the scaffold. It has been held that when the body of a claim fully and intrinsically sets forth all limitations of the claimed invention, such as all the components of a composition, and the preamble merely states the intended use of the invention, rather than any distinct definition of the any of the claimed invention’s limitations, the preamble is not considered a limitation and is of no significance to claim construction. See MPEP § 2111.02. To be applicable the prior art product must only be shown to be suitable for the intended use, but disclosure of use of the prior art product in said intended use is not necessary. In the instant case, the scaffold must be comprised of a nanocellulose and a polymer hydrogel, which upon mixing form a three-dimensional hydrogel that are suitable for culturing cells or tissues.
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, 6-7,9, 11, 14-15, and 17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Naseri et al (Royal Society of Chemistry, 2016)
Regarding claim 1, Naseri et al disclose a three-dimensional porous scaffolds for cartilage regeneration. The porous scaffold comprises of cellulose nanofibers and a polymeric hydrogel comprising of gelatin/Chitosan matrix. Naseri et al teach that the matrix (i.e. gelatin and chitosan) is crosslinked with genipin. Naseri et al teach that the gelatin/chitosan is a hydrogel-forming polymer system, and refer to it as a matrix, and the cellulose nanofibers are incorporated into the matrix to form three-dimensional scaffold. Naseri et al further teach that the resulting scaffold is subsequently frozen and freeze-dried to produce porous scaffold. Accordingly, Naseri et al teach a scaffold comprising of nanocellulose and a polymer hydrogel. ( See the Methods- section “ Processing of the nanocomposite scaffolds” on page 6000). It should be noted that the recitation of “ cultured meat scaffold” does not distinguish the claimed scaffold from the scaffold of Naseri et al because the phrase identifies an intended use. ( See claim interpretation above).
Regarding claim 2, Naseri et al teach that the nanocellulose are prepared in the form of suspension and then subsequently concentrated to obtain a gel. ( See the Methods-section “ Processing of cellulose nanofibers” on page 6000).
Regarding claim 3, Naseri et al expressly disclose nanocellulose fibers having diameter 19-38 nm, the dimension of which falls within the claimed range (i.e. 1nm-10um). ( See the Methods-section “ Processing of cellulose nanofibers” on page 6000).
Regarding claim 6, Naseri et al expressly disclose a gelatin/chitosan polymer matrix incorporated with nanocellulose. The gelatin/chitosan matrix is crosslinked with genipin and forms the polymer component of the three-dimensional scaffold. ( See abstract).
Regarding claim 7, Naseri et al also teach the use of a polymer hydrogel that is in the bulk form.
Regarding claim 9, according to table 1, Naseri et al teach the generation of different scaffolds, and report that the disclosed scaffolds have pore sizes that were generally within 20-200 um, which falls within the claimed range of 50 um -500 um. Naseri et al also report that all of the scaffolds were highly porous, with porosity greater than 93%, which also falls within the claimed range of 70-95% porosity. In table 1, Naseri et al report a X-CNF4-M2.2 scaffold having an average pore size of 59 um with a standard deviation of 18 (i.e. ± 18), which falls within the claimed range of 50-500 um, and a porosity of 94.2%. The relative variation of pore size (i.e. uniformity) when calculated is around 30.5% (i.e. 18/59* 100= 30.5%). Thus, the disclosed pore uniformity falls within the claimed range of 10-40%. Moreover, Naseri et al expressly teach homogeneity of the pore structure, and state that X-ray tomography showed that the pores are uniformly distrusted throughout the scaffold. ( See table 1, Fig.7C, and Fig.3a-c)
Regarding claims 11, Naseri et al expressly teach the method of instant claim. For example, the method of Naseri involves processing cellulose to produce nanocellulose in the form of gel. Then the nanocellulose is mixed with the gelatin/chitosan polymer matrix. The resulting scaffold is then frozen and freeze-dried to form the porous three-dimensional scaffold. ( See the Methods, sections “ Processing of cellulose nanofibers” , and “ Processing of the nanocomposite scaffolds”).
Regarding claims 14-15, and 17, Naseri et al disclose a three-dimensional porous scaffold according to the method of instant claim 11, and teach culturing cells on the scaffold. Thus, Naseri et al anticipates claim 14. Naseri et al further teach using the three-dimensional scaffold as a cell-supporting tissue-engineering scaffold. Specifically, Naseri et al teach culturing chondrocytes on the scaffold for 7 days at 37C/5% CO2. Naseri et al also teach performing an MTT assay to identify viable cells and report that chondrocytes in the scaffold remined viable after seven days and characterize the material as non-cytotoxic. With respect to the claim limitation of at least 80% viable, Naseri et al teach that the chondrocytes remained viable even after being in culture for 7 days. Therefore, the MTT assay provide direct evidence of the viability of cells maintained on the claimed -type scaffold. Naseri et al also expressly state that “When cells seeded on biomaterial surface, they attached to the scaffold. However, the cells retained the circular morphology up to day 6, but showed no sign of zone of inhibition or reduced growth”. ( See 1st column- 2nd pargraph on page 6006). The statement that the cells showed no sign of reduced growth suggests that the claimed level of cell activity (i.e. cell growth) of 20% or more is inherent in Naseri et al’s disclosure.
Claims 1-2, 5, 8, 10, and 14-16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Malandain et al (Applied Biomaterials, published 09/05/2023).
Regarding claims 1 and 6, Malandain et al disclose a three-dimensional scaffold comprising of type I collagen and bacterial nanocellulose fibers (BCF). Malandain et al expressly teach that the nanocellulose fibers are incorporated into type I collagen hydrogel to produce reinforced scaffolds with mechanical properties suitable for three-dimensional cell culture. It should be noted that the recitation of “ cultured meat scaffold” does not distinguish the claimed scaffold from the scaffold of Malandain et al because the phrase identifies an intended use. ( See claim interpretation above). Accordingly, Malandain et al teach a scaffold comprising of nanocellulose and collagen type I hydrogel. ( See abstract).
Regarding claim 2, Malandain et al teach that the nanocellulose are prepared in the form of suspension . ( See the Methods-section “ Bacterial Nanocellulose Fibers (BCf).”).
Regarding claim 5, Malandain et al expressly state that the nanocellulose fiber are endotoxin-free. ( See 1st column-3rd pargraph- on page 3639).
Regarding claim 8, Malandain et al disclose a selected hydrogel composition containing 74% type I collagen and 26% bacterial nanocellulose fibers, corresponding to 70% w/w/ Col-I, and 0,25% w/w BCF), by dividing the weight ratio of fibers to the polymer , i.e. 26/74 , this gives a ratio of = 0.351:1. It should be noted that the recited ranges 1:4 is equivalent to = 0.25:1, and the 3/2= 1.5:1. Thus the disclosed ratio 0.351:1 falls within the claimed range of 0.25:1- 1.5:1. ( See section “ Col-I/BCf Hydrogel Scaffold Development” on page 3640).
Regarding claim 10, Malandain et al disclose a defined Col-I/BCF composition comprising 26% nanocellulose and 74% polymer hydrogel, which as discussed in claim 8 falls within the claimed range for the required ratio. it is noted that instant specification expressly recognizes that the density and strength of the scaffold are controlled by the addition of nanocellulose and, more particularly by the mixing ratio of nanocellulose and polymer hydrogel. ( See instant specification page 8-lines 20-24). Because Malandain et al disclose a scaffold comprising nanocellulose and teach a mixing ratio for the nanocellulose/polymer that overlaps with the claimed range, the resulting density and mechanical properties are necessarily present in the disclosed scaffold. Absent evidence to the contrary and the claim is considered anticipated.
Regarding claims 14-16, following the discussion of claim 1 above, Malandain et al disclose a three-dimensional scaffold comprising of type I collagen and bacterial nanocellulose fibers (BCF). Malandain et al also disclose the incorporation of human bone-marrow derived mesenchymal stem cells into the scaffold. Specifically, Malandain et al teach that the cells were incorporated into the progel, the progel was gelled at 37C, and the resulting cell-laden three-dimensional scaffolds were cultured for seven days. Malandain et al further report measuring cell viability and proliferation by staining live/dead cell, over the seven-day in culture and state that “ hydrogel compared to Col-I do not affect cell viability and growth”. ( See Fig.5B, and section “ Viability of hBM-MSCs 3D Cultured in Col-I/BCf Scaffolds”).
Claims 1-2, 4, 6, and 11-13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ooi et al (Materials, 2020).
Regarding claims 1-2, 6, and 11-13, Ooi et al disclose a bilayer bioscaffold comprising of type I collagen and palm-tree-derived nanocellulose, this reads on claims 1 and 6. Ooi et al disclose combining ovine tendon collagen type I with palm-tree-based nanocellulose to form hybrid scaffold. The resulting scaffold has a three-dimensional interconnected porous structure and is subsequently cross-linked with genipin. Ooi et al also teach that the nanocellulose is in the form of powder, this reads on claim 2. ( See abstract, and section 2.2. “Nanocellulose Preparation”). Accordingly, Ooi disclose the claimed scaffold comprising nanocellulose and a polymeric collagen matrix. As noted previously, the recitation of “ cultured meat scaffold” does not distinguish the claimed scaffold from the scaffold of Ooi et al because the phrase identifies an intended use. ( See claim interpretation above). Ooi et al further teach preparing nanocellulose from cellulose, combining the resulting nanocellulose with collagen (i.e. polymer hydrogel); placing the mixture in a mold; and freezing-drying the resulting mixture for 24-48 hours to produce the scaffold, this reads on claims 11 and 13. ( See section 2.3. “Fabrication of Bilayer Hybrid Scaffold”). Ooi et al also disclose isolating nanocellulose by acid hydrolysis using 60% aqueous sulfuric acid for 40 minutes at 45C. Following hydrolysis, the resulting suspension is centrifuged, dialyzed against distilled water until constant PH is reached, and ultrasonicated to disentangle the resulting nanocrystal. ( See section 2.2. “Nanocellulose Preparation”). It should be noted that the disclosed treatment involves heating at a temperature of 45C which falls within the claimed range of 20-50 C, and the disclosed treatment of 40 minutes fall with the claimed range of 30 mins to 3 hours. The centrifugation and dialysis steps disclose washing/removal of the acid treatment medium, and the ultrasonication provides the claimed nanotization step. Accordingly, Ooi et al teach the method steps of claim 12.
Regarding claim 4, Ooi et al do not expressly disclose the numerical viscosity for the nanocellulose hydrogel. However, the nanocellulose is prepared using the same treatments condition disclosed in instant specification and identified in the disclosure as producing nanocellulose having viscosity suitable for a scaffold. Specifically, instant specification discloses that treatment of cellulose at a temperature of 20°C to 50°C for 30 minutes to 3 hours; followed by a step of washing; and a step of a nanotization, and states that “ If the temperature and time in the step of treating the cellulose are beyond the above ranges, an issue may occur in preparing of a nanocellulose having a mechanical strength and viscosity suitable for a scaffold”. ( See instant specification page 11-lines 15-17). Accordingly, since Ooi et al teach the same preparation conditions, thus the nanocellulose of Ooi et al must inherently characterized as having a viscosity of 12,000 cp, and gelation time of 1-30 seconds. Absent evidence to the contrary and the claim is considered anticipated.
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.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
Claim(s) 8 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Naseri et al (Royal Society of Chemistry, 2016).
The teachings of Naseri et al are set forth above. Naseri et al anticipates claims 1-3, 6-7,9, 11, 14-15, and 17.
Regarding claim 8, Naseri et al expressly identifies the fibers/matrix ratio as a variable that was varied to tailor the scaffold’s properties. Specifically, Naseri et al disclose varying the fiber/matrix ratio, along with suspension concentration and crosslinking, to tailor the pore size structure and porosity of the scaffold and to obtain optimal mechanical properties. ( See 1st column-2nd paragraph- lines 19-24-on page 6000). Thus, the fibers/matrix ratio is expressly recognized by Naseri et al as a result effective variable. It is well recognized that it is prima facie obvious for one of ordinary skill in the art to use routine experimentation to discover an optimum value of a result effective variable. According to the MPEP, "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation. The "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Application of Boesch, 617 F.2d 272, 276, 205 USPQ 215, 218-219 (C.C.P.A. 1980). See MPEP 2144.05. Absent evidence to the contrary and the claim is considered obvious.
Regarding claim 10, following the discussion of claim 8 above, Naseri et al recognize that density, porosity, and mechanical strength as interrelated scaffold properties and expressly teach varying scaffold-processing and compositional parameters to tailor these properties for cartilage regeneration. Accordingly, the claimed density, and mechanical properties would have been subject to optimization in designing the scaffold to obtain the desired parameters depending on the particular cell or tissue to be supported. An ordinary skill in the art would have understood that the appropriate scaffold composition and resulting physical and biological properties would depend on the particular intended use, such as cartilage regeneration or supporting the growth of cultured meat. Therefore, it would have been a prima facie obvious for one of ordinary skill in the art to use routine experimentation to discover an optimum value of a result effective variable. Absent evidence to the contrary and the claim is considered obvious.
Conclusion
No claim is allowed.
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/FATIMAH KHALAF MATALKAH/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
