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 .
Claims 1-20 are pending, all of which have been considered on the merits.
Priority
Acknowledgement is made of Applicants’ claim for benefit of prior-filed US Provisional application 63/427937 (filed 11/25/2022).
Claim Interpretation
The claims use the term structured fat. There is no specific definition in the specification for the term structured fat. Thus the term is being interpreted as meaning fat tissue with a 3D structure.
Claim 1 is drawn to a composition comprising 3D structured fat. The claim defines the fat using product-by-process limitations. Product-by-process limitations are considered only insofar as the method of production imparts distinct structural or chemical characteristics or properties to the product. Therefore if the product, as claimed, is the same or obvious over a product of the prior art (i.e. is not structurally or chemically distinct), the claim is considered unpatentable over the prior art, even though the prior art product is made by a different process. See MPEP 2113.
In the instant case, claim 1 states the 3D structured fat is made by optimizing and/or using one or more of parameters a)-f). It is emphasized that the broadest reasonable interpretation only requires a single one of the parameters to be optimized and/or used. For the reasons set forth below under 35 USC 112(b), it is not clear what optimization entails, as no final structure or goal is set forth. Thus, the broadest reasonable interpretation will be that the method of production involves:
any sterilization protocol;
selection and identifying of any matrix;
identification, isolation and proliferation of any cell;
identification of an animal derived serum, or use of minimal serum or no serum;
use of any method which will cause cell proliferation;
developing a quantitative non-invasive method for ascertaining cell proliferation and/or adhesion (note: the non-invasive method need not be employed, but rather simply developed. This reads on a mental step)
None of a)-f) clearly impart any specific structural or physical feature to the final 3D structured fat. Therefore, claim 1 is interpreted as covering any fat tissue with a 3D structure.
Claim 2 specifies that all of parameters a)-f) are employed in the method of production. As above, because none of a)-f) clearly impart any specific structural or physical feature to the final 3D structured fat, even requiring all of a)-f) to be used will not affect the final structure. Therefore claim 2 is interpreted as covering any fat tissue with a 3D structure.
Claim 3 is interpreted as being directed to a fat tissue with a 3D structure comprising a plant-based matrix.
Claim 4 is interpreted as being directed to a fat tissue with a 3D structure comprising a plant-based matrix that comprises at least some soy-based components.
Claim 5 is interpreted as being directed to a fat tissue with a 3D structure comprising MSC and progenitor cells. It is noted that MSCs can be considered progenitor cells.
Claims 6-7 are interpreted as being directed to a fat tissue with a 3D structure. The requirement that the method of production uses some proteases in some way during some part of preparation is insufficient to impart any specific physical or chemical properties to the final product.
Claim 8 is interpreted as being directed to a fat tissue with a 3D structure. Claim 1 d) permits for serum to be used, or not used. Claim 8 does not specifically require the serum to be used. Even if the method of production does require use of serum comprising one or more of glutathione, TGFß1 or FGF2, the use of serum in some way during some part of the preparation is insufficient to impart any specific physical or chemical properties to the final product.
Claim 9 is interpreted as being directed to a fat tissue with a 3D structure. Measuring a parameter of the fat tissue does not change the physical or chemical properties of the tissue.
Claim 10 is interpreted as being directed to a fat tissue with a 3D structure and comprising a plant-based matrix comprising at least some components derived from soy, and comprising ADSCs.
Claim Objections
Claim 5 is objected to for a minor informality: Claim 5 is the first use of the abbreviations “MSC”, “ADSC” and “FAPs”. The full term should precede the first use of an abbreviation. It would be remedial to amend claim 5 to say “…wherein the ideal cells are mesenchymal stem cells (MSC) and progenitor cells, such as Adipose derived stromal cells (ADSCs) and fibro-adipogenic precursors (FAPs).
Setting forth the full term in claim 5 will permit use of the abbreviations in subsequent claims (e.g. claims 10, 14, 20).
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-20 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 1: The claim describes a 3D structured fat, which is interpreted as being a fat tissue with 3D structure. The claim uses product-by-process language. The product-by-process language is unclear because it states the method involves optimizing one or more of the parameters a)-f). Because there is no clear end goal (e.g. a specific structure, size, cell concentration, etc), it is unclear what is being optimized. Even for parameter a) optimizing sterilization protocol, it is unclear if it is optimizing for sterility, for cost, for time, or otherwise.
Furthermore, in parameter b) the term ideal matrix is a relative term which renders the claim indefinite. The term ideal is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is not clear what makes a matrix ideal.
Reference to ideal cells in parameter c) and ideal cell proliferation in parameters e) and f) suffer the same deficiency.
Claims 2-10 depend from claim 1, inherit the deficiencies, and are rejected on the same basis. It is noted that claims 2, 5, and 10 also use the phrases ideal matrix, ideal cells, and ideal cell proliferation.
Regarding claim 5, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 11: Like in claim 1, it is unclear what is being optimized in step a) (optimized for sterility? Optimized for cost? Time? Etc).
Like in claim 1, the terms ideal cells (steps c, d and f) and ideal matrix (step b) are problematic because they are relative terms with no basis to determine what would be considered ‘ideal’. This issue persists with reference to the same in claims 12, 14, and 20.
Regarding claim 14, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 2 and 5-9 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature judicial exception without significantly more.
The claims have been analyzed for eligibility in accordance with their broadest reasonable interpretation.
Regarding claim 1: The claim is directed to fat tissue with a 3D structure. The claim reads on intact adipose tissue. Intact adipose tissue has a 3D structure (See Papadopoulos and Edwards, J Oral Maxillofac Surg, 2009; Fig. 4).
The claim is directed to a composition, which is a statutory category of invention (Step 1: YES).
Intact adipose tissue is a nature-based product, and as such is compared to its closest naturally occurring counterpart to determine if it is markedly different from said closest naturally occurring counterpart. The closest naturally occurring counterpart to intact adipose tissue is natural adipose tissue. Natural adipose tissue exists in the mammalian body, and can be excised intact (See Eto et al, Pg 1088, “Human Tissue Sampling”, describing the excised adipose tissue). There is no difference between the intact adipose tissue claimed and adipose tissue in the mammalian body, nor between intact adipose tissue claimed and excised intact adipose tissue, as en bloc excision does not change the structure or cellular content of the tissue. Thus the claim does recite a product of nature judicial exception (Step 2A, Prong 1: YES).
The claim does not integrate the product into a practical application because the claim is to the composition, per se, not a method of use. (Step 2A, Prong 2: NO).
The claim does not recite any elements in addition to the judicial exception, intact adipose tissue, so there are no additional elements that add significantly more to the judicial exception (Step 2B: NO).
The claim is patent ineligible.
Regarding claims 2 and 6-9: The broadest reasonable interpretation of claims 2 and 6-9 are the same as claim 1. Thus the analysis for claims 2 and 6-9 are the same as above. Claims 2 and 6-9 are patent ineligible.
Regarding claim 5: Claim 5 is interpreted as requiring the 3D structure fat to comprise MSCs. Naturally occurring intact adipose tissue contains adipose derived stromal cells (which are MSCs) (See Eto et al, Fig. 8, describing the excised adipose tissue). Thus the analysis for claim 5 is the same as above. Claim 5 is patent ineligible.
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.
Claims 1, 2 and 5-9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Eto et al (Plastic and Reconstructive Surgery, 2009).
Eto et al disclose excised (intact) adipose tissue (See Pg 1088, “Human Tissue Sampling”).
Regarding claims 1, 2, and 6-9: Pursuant to the Claim Interpretation section above, each of these claims are interpreted as being drawn to fat tissue with a 3D structure. The excised (intact) adipose tissue reads on fat tissue with a 3D structure.
Regarding claim 5: Following the discussion of claim 1 above, the excised (intact) fat tissue contains ADSCs (See Eto et al, Fig. 8). ADSCs are MSCs.
Claims 1-3, 5-9, 11, 12, and 14-17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ianovici et al (Biomaterials, 2022 (epub March 2022)), evidenced by Cytiva “Growth factors in serum products: HyClone Sera” (2020).
Ianovici et al disclose use of 3D printable plant protein-enriched scaffolds for cultured meat development.
The embodiment relied upon for this rejection is the 3D printed cellular construct comprising bovine adipose tissue-derived MSCs (BMSCs) in RGD-modified alginate (Alginate(RGD)) + pea denatured protein isolate (PPI) (See “2.3. Design and fabrication of 3D-printed constructs”). Ianovici et al report culturing the construct to achieve differentiation of BMSCs into mature adipocytes (See “2.9. Cell Culture protocols”).
Regarding claims 1, 2 and 6-9: Pursuant to the Claim Interpretation section above, each of these claims are interpreted as being drawn to fat tissue with a 3D structure. The final construct after culture (containing mature adipocytes) reads on a composition comprising 3D structured fat. The construct is a fat tissue, as it contains adipocytes, and it is 3D.
Regarding claim 3: Following the discussion of claim 1 above, the 3D cellular construct comprises a matrix comprising pea denatured protein isolate, which is a plant based matrix.
Regarding claim 5: Following the discussion of claim 1 above, the cells present in the construct include adipose-derived MSCs. At least some residual non-differentiated MSCs will be present during the production of the construct.
Regarding claim 11: The manner of producing the 3D printed cellular construct comprising BMSCs in the Alginate(RGD) + PPI scaffold involves:
The authors necessarily selected BMSCs and the Alginate(RGD) + PPI scaffold materials at design of their experiment. This reads on b) selecting and identifying an ideal matrix to be used, and c) identifying… ideal cells to be used.
BMSCs were isolated from peri-renal adipose tissue of a 1 year old calf carcass. The resected tissues were soaked in sterile PBS supplemented with 3% penicillin-streptomycin-nystatin (PSN) solution (See “2.8. Primary bovine cells isolation”). The tissue was then minced, digested with collagenase, filtered, pelleted, then plated in BMSC medium (DMEM-HG + 10% FBS). After 4 days of culture, the cells were washed with PBS to remove unattached cells and cultured in fresh medium. At 80% confluence, the cells were harvested with 0.25% trypsin EDTA (See id).
The step of washing the resected tissues in PSN solution reads on a) optimizing sterilization protocol, as antibiotics and antimycotics were used to reduce bioburden.
The step of using DMEM-HG plus 10% FBS reads on d) identifying and using animal-derived serum.
The steps of isolating, culturing and expanding the cells reads on the remaining part of c) [identifying,] isolating and proliferating ideal cells to be used, as well as e) using one or more methodologies to enhance the ideal cell proliferation.
The step of monitoring cell confluency status reads on f) developing a quantitative non-invasive method for ascertaining the ideal cell proliferation, as it monitors cell proliferation rate.
The expanded BMSCs were then mixed with the Alginate(RGD) + PPI bioink and extrusion bioprinted into a cellular construct. The cellular constructs were then further cultured in BMSC medium, then transferred to adipogenic differentiation medium, then transferred to adipogenic maturation medium, to ultimately obtain BMSCs differentiation into mature adipocytes (See “2.9. Cell culture protocols”).
As discussed above with regards to claim 1, the final constructs read on 3D structured fat.
Regarding claim 12: Following the discussion of claim 11 above, the matrix includes PPI, which is a plant-based matrix.
Regarding claim 14: Following the discussion of claim 11 above, the selected cells include adipose-derived MSCs.
Regarding claims 15-16: Following the discussion of claim 11 above, the method of making the cellular construct involves expanding the BMSCs in culture, which involves harvesting the cells using trypsin, which is a serine protease.
Regarding claim 17: Following the discussion of claim 11 above, the method of making the cellular construct involves expanding the BMSCs in culture, which involves use of BMSC medium (DMEM-HG + FBS). Cytiva is relied upon to evidence that HyClone FBS contains TGFß and FGF2 (see Table 2).
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.
Claims 4, 10 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Ianovici et al (Biomaterials, 2022 (epbub March 2022)), evidenced by Cytiva “Growth factors in serum products: HyClone Sera” (2020).
The teachings of Ianovici et al are set forth above.
Regarding claims 4, 10 and 13: Ianovici et al test two plant-based proteins for production of the protein-polysaccharide 3D-bioprintable scaffolds: pea denatured protein isolate (PPI) and soy denatured protein isolate (SPI) (each used in combination with Alginate(RGD)) (See Pg 2, paragraph spanning col. 1-2, and Pg. 7 “3.2.1 Extrusion printing process development”). Ianovici et al teach both the Alginate(RGD)-PPI and Alginate(RGD)-SPI equally enabled a flexible and controlled 3D material deposition and construct fabrication.
Ianovici et al only go on to test BMSCs in the Alginate(RGD) + PPI material, they do not exemplify BMSCs in the Alginate(RGD) + SPI material. Thus, Ianovici et al does not clearly teach a composition comprising 3D structured fat comprising a matrix comprising soy-based material as required by claims 4, 10 and 13.
However, Ianovici et al report the Alginate(RGD) + PPI and Alginate(RGD) + SPI as equivalent in ability to 3D print and to support cell culture (See Pg 14, col. 1). Therefore, while not exemplified, the teachings of Ianovici et al support equivalency of PPI and SPI as the plant-based protein component. As such, it would have been prima facie obvious to have substituted SPI for the PPI in the 3D printed cellular constructs containing BMSCs of Ianovici et al. Based on the recognized equivalency of PPI and SPI by Ianovici et al, one would have expected equivalent success in growing a maturing the BMSCs into mature adipocytes. As such, claims 4, 10 and 13 are considered obvious over Ianovici et al.
Claims 18-20 are rejected under 35 U.S.C. 103 as being unpatentable over Ianovici et al (Biomaterials, 2022 (epbub March 2022)), evidenced by Cytiva “Growth factors in serum products: HyClone Sera” (2020), in view of Borschevskaya et al (J Anal Chem, 2016).
The teachings of Ianovici et al are set forth above.
Regarding claims 18-20: Following the discussion of claims 11 (for claims 18-19) or claim 13 (for claim 20), Ianovici et al differ from the current claims in that Ianovici et al does not teach measuring a quantity of lactate using a standard curve.
However, Ianovici et al is directed towards generation of cell-based food products. Borshchevskaya et al teach that monitoring of lactate in food products is part of quality control (See Pg 755, col. 1). Therefore, it would have been prima facie obvious to have monitored the lactate in the cultural liquid of the BMSC-containing cell construct of Ianovici et al to monitor suitability for subsequent consumption. This conclusion of obviousness is based off a teaching in the prior art.
Borshchevskaya et al teach a rapid spectrophotometric method for determination of L- and D-isomers of lactic acid (which is the acid form of lactate) in cultural liquids (See Pg 755, col. 2). The details of the method are outlined at Pg 756 “Experimental”, and include use of iron(III) chloride and construction of a calibration curve (which reads on standard curve). The lactate is measured at a wavelength of 390 nm (See Pg 756, col. 2).
The spectrophotometric method of Borshchevskaya et al satisfies the limitation of developing a quantitative non-invasive method for ascertaining the ideal cells and/or adhesion, wherein the method comprises measuring a quantity of lactate using a standard curve, wherein the lactate is measured at a wavelength of… 390 nm.
One would have had a reasonable expectation of success because Borshchevskaya et al provide specific guidance on how to perform the measurements.
Conclusion
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/ALLISON M FOX/Primary Examiner, Art Unit 1633
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