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 .
Claim Status
Claims 4, 6-16, 18-31, 34-38, 40-46, 49, 51-52, 55, 57-59, 61-71, 73-87, 89-93, 95, 97-99, and 101-108 have been canceled, claims 1, 3, 5, 17, 32-33, 39, 47-48, 50, 53-54, 56, 60, 72, 88, 94, 96, and 100 are currently amended, and claims 1-3, 5, 17, 32-33, 39, 47-48, 50, 53-54, 56, 60, 72, 88, 94, 96, and 100 have been considered on their merits.
Claim Objections
Claims 1, 47, and 96 are objected to because of the following informalities: the claims recite the limitation “…average of least 450%...”. This is an apparent typographical error intended to read as “at least 450%”. The instant specification also recites this same “of least 450%” language.
Appropriate correction is required.
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.
Claims 1-3, 5, 17, 32-33, 39, 47-48, 50, 53-54, 56, 60, 72, 88, 94, 96, and 100 are 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.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. An original claim may lack written description support when (1) the claim defines the invention in functional language specifying a desired result but the disclosure fails to sufficiently identify how the function is performed or the result is achieved or (2) a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349-50 (Fed. Cir. 2010) (en banc). The written description requirement is not necessarily met when the claim language appears in ipsis verbis in the specification. “Even if a claim is supported by the specification, the language of the specification, to the extent possible, must describe the claimed invention so that one skilled in the art can recognize what is claimed. The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement.” Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002).
For claims drawn to a genus, possession may be shown (for example) through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. A “representative number of species” means that the species which are adequately described are representative of the entire genus, and is an inverse function of the skill and knowledge in the art. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly. If a representative number of adequately described species are not disclosed for a genus, the claim to that genus must be rejected as lacking adequate written description under 35 U.S.C. 112(a). Also see MPEP § 2163.
The scope of the claims does not commensurate with the possession demonstrated by the disclosure with regard to the extremely large number of species broadly encompassed by the claims.
Actual Reduction to Practice
Regarding claim 1, encompassing a method comprising exposing an undefined number of any cell to any cell culture media comprising any concentration of whey protein and growing said cells for an unknown length of time in said culture media comprising whey. The claim also recites an intended result of an increase in size of [at] least 450% relative to the size of the plurality of cells prior to exposing the cells to the cell culture media comprising whey. The claim limitations are directed to an extremely broad genus of any cell, which would include any bacterial, fungal, or mammalian cell; as well as any concentration of whey protein.
Regarding claims 5 and 60, encompassing various types of cells to include myoblasts, fibroblasts, adipocytes, vascular cells, osteoblasts, tenocytes, epithelial cells, mammalian gland cells, neural cells, embryonic stem cells, induced pluripotent stem cells, and/or adult stem cells. These cell types represent a diverse number of species which would require specific cell culture conditions to potentially achieve the intended result of [at] least 450% relative increase in size.
Regarding claims 17 and 72, encompassing a limited number of eukaryotic cells species, while still broad to encompass various mammalian cells as well as reptile cells.
Regarding claim 47, encompassing a method comprising exposing a plurality of any cell to a culture media for 24 hours followed by exposing said cells to a second culture media comprising whey protein and growing said cells in the second culture media. Claim 47 also recites the intended result of [at] least 450% relative increase in size. While this claim further defines the timing of a first cell culture media exposure as compared to claim 1, this claim is still extremely broad to include any type of cell and any concentration of whey protein.
Regarding claim 96, encompassing a method comprising obtaining milk product from a mammal, extracting whey protein from said milk product, forming a cell culture media comprising said whey protein, culturing any cells in said media, and growing said cells in said cell culture media comprising whey protein. Claim 96 also recites the intended result of [at] least 450% relative increase in size.
The specification provides no examples of a method comprising exposing an undefined number of any cell to any cell culture media comprising any concentration of whey protein and growing said cells in said culture media comprising whey. Rather, the specification only discloses one example, starting on page 13 of the instant specification. In this example, Applicant has conducted an assay wherein the size and density of bovine skeletal muscle cells were cultured in DMEM comprising either FBS or varying defined concentrations of whey protein. Applicant describes a defined basal media composition, cell density, and culture conditions to include the length of time, wherein the cells were able to proliferate in whey protein/DMEM, with 2% whey yielding the greatest degree of proliferation and demonstrated an increased size of individual cells. Thus, the specification only provides a reduction to practice involving one species of cell and defined concentrations of whey protein in the cell culture media.
Accordingly, Applicant did not demonstrate a reduction to practice of a method comprising exposing an undefined number of any cell to any cell culture media comprising any concentration of whey protein and growing said cells in said culture media comprising whey.
State of the Art and Quantity of Experimentation
The method of culturing cells in media comprising whey is well-known in the art, however, successfully culturing different cell types result in varying degrees of success depending on whey concentration and the cell being cultured. However, the claimed invention is not well established, because a method comprising exposing an undefined number of any cell to any cell culture media comprising any concentration of whey protein and growing said cells in said culture media comprising whey and achieving an intended result of [at] least 450% relative increase in size.
Regarding the state of the art, as evidenced by Francis et al. (J Dairy Sci 78:1209-1218, 1995). Francis teaches whey was investigated as a source of growth-stimulating factors that might replace or supplement fetal bovine serum in cell culture (Abstract). Francis teaches extracts comprising only 1 to 2% of whey protein displayed substantial growth-promoting activities on Balb/c 3T3 cells, L6 myoblasts, and human skin fibroblasts (Abstract). Francis teaches the rat myoblasts were cultured in a medium comprising whey samples diluted with Dulbecco’s PBS to measure protein synthesis (p. 1210, 2nd column). Francis teaches the 400 mM NaCl eluate produced higher growth rates on a protein basis in Balb/c 3T3 cells, L6
myoblasts, and human skin fibroblasts (Fig. 4 and p. 1213, 1st column). Francis teaches this fraction induced cell growth with higher potency than FBS in the myoblasts and was 5 to 20 fold more potent than FBS in the other two cell lines (p. 1213, 1st column). Thus, demonstrating specific culture conditions, to include whey protein concentration, are required to obtain the claimed intended results. Also, Francis teaches this result is only seen in myoblasts and not in mouse or human fibroblasts.
Paradkar et al. (Indian Journal of Experimental Biology, Vol. 57, February 2019, pp. 123-130, IDS ref.) teaches methods of culturing cells comprising bovine whey protein as an alternative to FBS in supplementing cell culture media (Abstract). Paradkar teaches an assay wherein cell viability, growth, and cytotoxicity was determined (p. 125, SRB assay). Paradkar teaches 1 x 103 CHO-K1 cells were seeded in 96-well plates and cultured for 24 hours (p. 125, SRB assay). Paradkar teaches on the following day fresh media comprising bovine whey protein (BWP) and FBS in different concentrations and cultured for up to 72 hours (p. 125, SRB assay). Paradkar teaches when BWP was used as a replacement of FBS in CHO K1 and Jujkat cells, it was shown that the cell growth rate declined as BWP concentration increased with declining FBS levels in the culture media (p. 125, Cell viability assay and Fig. 3).
Therefore, although, culturing cells in media comprising whey was known in the state of the art, one of skill in the art would neither expect nor predict the appropriate functional change in a method comprising exposing an undefined number of any cell to any cell culture media comprising any concentration of whey protein and growing said cells in said culture media comprising whey and achieving an intended result of [at] least 450% relative increase in size.
Thus, the method comprising exposing an undefined number of any cell to any cell culture media comprising any concentration of whey protein and growing said cells in said culture media comprising whey and achieving an intended result of [at] least 450% relative increase in size was not well established
Thus, it appears any claimed functional outcome in an intended result of [at] least 450% relative increase in size in cells culture in culture media comprising whey protein, requires a specific cell type and conditions in order to be achieved.
Conclusion
Applicant has claimed method comprising exposing an undefined number of any cell to any cell culture media comprising any concentration of whey protein and growing said cells in said culture media comprising whey and achieving an intended result of [at] least 450% relative increase in size, yet the specification has not disclosed a method comprising exposing an undefined number of any cell to any cell culture media comprising any concentration of whey protein and growing said cells in said culture media comprising whey and achieving an intended result of [at] least 450% relative increase in size. Rather, the specification demonstrates an assay wherein the size and density of a specific cell type, bovine skeletal muscle cells, were cultured in a defined media with defined concentrations of whey protein which yielded the greatest degree of proliferation and demonstrated an increased size of individual cells.
Accordingly, neither the specification nor the prior art establishes a known structure-function relationship wherein the genus of any cell in any cell culture media comprising any concentration of whey protein and are capable of providing for the function as claimed with any predictability. The prior art highlights the structural importance of cell type and whey protein concentration, which would be tied to the structure function relationship. In this case, the skilled artisan would not have reasonably concluded at the time of the invention that application was in possession of the invention as claimed.
The dependent claims are included in the rejection because they do not remedy the issues.
Claims 1-3, 5, 17, 32-33, 39, 47-48, 50, 53-54, 56, 60, 72, 88, 94, 96, and 100 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of culturing myoblasts in a cell culture media comprising 2% whey protein to achieve an intended result of an increase in at least 450% in cell size relative to the myoblasts prior to exposing the cells to the cell culture media, does not reasonably provide enablement for a method comprising exposing an undefined number of any cell to any cell culture media comprising any concentration of whey protein and growing said cells in said culture media comprising whey and achieving an intended result of [at] least 450% relative increase in size.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The factors to be considered in determining whether undue experimentation is required are summarized in In re Wands, 858 F.2d 731, 737, 8 USPQd 1400, 1404 (Fed. Cir. 1988) (a) the breadth of the claims; (b) the nature of the invention; (c) the state of the prior art; (d) the level of one of ordinary skill; (e) the level of predictability in the art; (f) the amount of direction provided by the inventor; (g) the existence of working examples; and (h) the quantity of experimentation needed to make or use the invention based on the content of the disclosure. While all of these factors are considered, a sufficient number are discussed below so as to create a prima facie case.
The breadth of the claims
The instant claims disclose a method comprising exposing any cell to any cell culture media comprising any concentration of whey protein and growing said cells in said culture media comprising whey and achieving an intended result of [at] least 450% relative increase in size.
The scope of any cell includes any cell from any organism to include bacterial, fungal, plant, or mammalian cells. The scope of the concentration of whey protein in the culture media would include concentrations which would be considered cytotoxic to cells in culture. The instant specification discloses one example wherein bovine myoblasts are cultured in a media with a defined concentration of whey protein.
The nature of the invention
The instant invention is a method of culturing myoblasts in a defined media comprising whey protein in order to achieve increased cell size, however, the scope of the claims do not limit the whey protein concentration until claim 53 and the cell type until claim 60, which is still broad to include several species of cell wherein the effects of increased whey protein in the media has not been evaluated.
The state of the prior art and level of predictability
Francis et al. (J Dairy Sci 78:1209-1218, 1995) teaches whey was investigated as a source of growth-stimulating factors that might replace or supplement fetal bovine serum in cell culture (Abstract). Francis teaches extracts comprising only 1 to 2% of whey protein displayed substantial growth-promoting activities on Balb/c 3T3 cells, L6 myoblasts, and human skin fibroblasts (Abstract). Francis teaches the rat myoblasts were cultured in a medium comprising whey samples diluted with Dulbecco’s PBS to measure protein synthesis (p. 1210, 2nd column). Francis teaches the 400 mM NaCl eluate produced higher growth rates on a protein basis in Balb/c 3T3 cells, L6 myoblasts, and human skin fibroblasts (Fig. 4 and p. 1213, 1st column). Francis teaches this fraction induced cell growth with higher potency than FBS in the myoblasts and was 5 to 20 fold more potent than FBS in the other two cell lines (p. 1213, 1st column). Thus, demonstrating specific culture conditions, to include whey protein concentration, are required to obtain the claimed intended results. Also, Francis teaches this result is only seen in myoblasts and not in mouse or human fibroblasts. Thus, highlighting that the intended outcome would be unpredictable in any cell.
Paradkar et al. (Indian Journal of Experimental Biology, Vol. 57, February 2019, pp. 123-130, IDS ref.) teaches methods of culturing cells comprising bovine whey protein as an alternative to FBS in supplementing cell culture media (Abstract). Paradkar teaches an assay wherein cell viability, growth, and cytotoxicity was determined (p. 125, SRB assay). Paradkar teaches 1 x 103 CHO-K1 cells were seeded in 96-well plates and cultured for 24 hours (p. 125, SRB assay). Paradkar teaches on the following day fresh media comprising bovine whey protein (BWP) and FBS in different concentrations and cultured for up to 72 hours (p. 125, SRB assay). Paradkar teaches when BWP was used as a replacement of FBS in CHO K1 and Jujkat cells, it was shown that the cell growth rate declined as BWP concentration increased with declining FBS levels in the culture media (p. 125, Cell viability assay and Fig. 3). Thus, demonstrating the unpredictability of culturing any type of cell at any concentration of whey protein.
Therefore, not all cells at any concentration of whey protein in a cell culture media would result in the intended result of an increase in cellular size. It would be highly unpredictable to expect any cell in a media comprising any concentration of whey protein would result in the predictable outcome of increased cell size.
In the absence of any working embodiments with regard to an increased size in any cell, other than myoblasts in a defined concentration of whey protein, the instant disclosure does not provide adequate enablement for culturing any cell in any cell culture media comprising whey protein at any concentration and expect the result of increased size of the cells relative to the cells prior to exposure to the culture media comprising whey protein.
Therefore, undue experimentations would be necessary for a person skilled in the art to use the claimed invention.
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.
Claim 39 is 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.
Claim 39 recites the limitation “further comprising adding a salt solution to the cell culture media to precipitate the whey protein to form the milk product”. Claim 32, from which claim 39 depends, recites the whey protein is obtained from a milk product. If the whey protein is obtained from a milk product, is the whey protein discussed in claim 39 utilized to make another milk product? It is unclear if the limitations in claim 39 is referring to the same milk product or a different milk product. The instant specification at page 3 states, "As discussed herein, milk proteins, e.g., whey protein, may be isolated from a milk product using techniques known to those of ordinary skill in the art, for example, acid-induced precipitation, salt-induced precipitation, and/or enzymatic treatment, which separates the milk product into a solid fraction and a liquid fraction."
Therefore, the claim will be interpreted in light of the specification to mean the whey protein is obtained from the milk product using a salt solution. However, it is also unclear if the method of obtaining whey protein is intended to limit the method of culturing the plurality of cells as a high sodium chloride concentration would cause excessive osmotic stress on the cells leading to cell death. Thus, the claim is interpreted as a method of obtaining whey from a milk product prior to cellular contact.
The language of a claim must make it clear what subject matter the claim encompasses to adequately delineate its "metes and bounds". See, e.g., the following decisions: In re Hammack, 427 F 2d. 1378, 1382, 166 USPQ 204, 208 (CCPA 1970); In re Venezia 530 F 2d. 956, 958, 189 USPQ 149, 151 (CCPA 1976); In re Goffe, 526 F 2d. 1393, 1397, 188 USPQ 131, 135 (CCPA 1975); In re Watson, 517 F 2d. 465, 477, 186 USPQ 11, 20 (CCPA 1975); In re Knowlton 481 F 2d. 1357, 1366, 178 USPQ 486, 492 (CCPA 1973).
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, 32-33, 47-48, 50, 53, 60, 88, 96, and 100 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kerasioti et al. (Food Chemistry 155 (2014) 271-278) as evidenced by Tu et al. (J. Proteome Res. 2018, 17, 2963−2977).
Regarding claim 1, Kerasioti teaches culturing muscle C2C12 cells in a culture medium comprising sheep whey protein (Abstract). C2C12 cells are known in the art as mouse myoblast cells. Regarding the limitation directed to the plurality of cells increase in size by an average of [at] least 450%, relative to the size of the plurality of cells prior to exposing the plurality of cells to the cell culture media, this limitation reads as an intended result of the claimed method. As such, this clause does not add structure to the method for exposing a plurality of cells to cell culture media comprising whey protein. MPEP § 2111.04 states “the court noted that a "‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’" Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)). Therefore, the teachings of Kerasioti read on the limitation of claim 1.
Regarding claims 2 and 3, Kerasioti teaches the C2C12 cells were cultured in DMEM medium and fetal bovine serum (Section 2.7). Fetal bovine serum is known to comprise insulin growth factor 1 and 2 as evidenced by Tu (Abstract).
Regarding claim 5, Kerasioti teaches the cells being cultured are C2C12 cells, which are myoblasts (Abstract).
Regarding claim 32, Kerasioti teaches the whey protein is obtained from sheep (Abstract). Whey is derived from the animals milk, thus, the product is obtained from a milk product.
Regarding claim 33, Kerasioti teaches the whey protein is obtained from sheep milk. As such the milk would necessarily be obtained from a pregnant and/or nursing mammal, as that is when mammals produce milk.
Regarding claims 47-48 and 50, Kerasioti teaches the C2C12 cells were cultured in DMEM medium and fetal bovine serum (a first cell culture media) (Section 2.7). Fetal bovine serum is known to comprise insulin growth factor 1 and 2 (claims 48 and 50) as evidenced by Tu (Abstract). Kerasioti teaches the C2C12 cells were subcultured in DMEM medium for 24 hours (claim 47) (Section 2.8). Kerasioti teaches after 24 hours the cells were treated with increasing concentrations of whey protein (a second cell culture media) (Section 2.8). Regarding the limitation directed to the plurality of cells increase in size by an average of [at] least 450%, relative to the size of the plurality of cells prior to exposing the plurality of cells to the cell culture media, this limitation reads as an intended result of the claimed method. As such, this clause does not add structure to the method for exposing a plurality of cells to cell culture media comprising whey protein. MPEP § 2111.04 states “the court noted that a "‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’" Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)). Therefore, the teachings of Kerasioti read on the limitation of claim 47.
Regarding claim 53, Kerasioti teaches C2C12 cells were seeded in 25 cm2 or 75 cm2 culture flasks and incubated for 24 h at 37 °C in 5% CO2, then the medium was removed and replaced with a medium comprising sheep whey protein at different concentrations, 0-6.24 mg of protein/ml (Section 2.9). The instant specification in Example 1, discloses the whey powder was suspended in DMEM at different concentrations and gives examples of 2%, 1%, and 0.5% w/v. Therefore, it is understood that 2% by mass would be converted to 20mg/ml and 0.5% would be converted to 5mg/ml. Therefore, Kerasioti teaches whey protein concentrations of between 0.5 and 2% by mass.
Regarding claim 60, Kerasioti teaches the plurality of cells are myoblasts (Abstract).
Regarding claim 88, Kerasioti teaches the whey protein is obtained from sheep milk (Abstract). Kerasioti teaches the whey protein is obtained from sheep milk. As such the milk would necessarily be obtained from a pregnant and/or nursing mammal, as that is when mammals produce milk. It is noted for the record that claim 88 recites the same limitations as claims 32 and 33, which also ultimately depend from claim 1.
Regarding claim 96, Kerasioti teaches culturing cells in a cell culture media comprising sheep whey protein, which reads as obtaining a milk product from a milk-producing animal. Kerasioti discloses including whey protein in the culture media, thus, they whey has been extracted from the milk product. Since Kerasioti teaches culturing a plurality of cells in a culture media comprising whey protein, this reads as forming cell culture media comprising whey protein, exposing a plurality of cells to the cell culture media, and growing the plurality of cells in the cell culture media. Regarding the limitation directed to the plurality of cells increase in size by an average of [at] least 450%, relative to the size of the plurality of cells prior to exposing the plurality of cells to the cell culture media, this limitation reads as an intended result of the claimed method. As such, this clauses does not add structure to the method for exposing a plurality of cells to cell culture media comprising whey protein. MPEP § 2111.04 states “the court noted that a "‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’" Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)). Therefore, the teachings of Kerasioti read on the limitation of claim 96.
Regarding claim 100, Kerasioti teaches the whey is from sheep (Abstract), a milk-producing mammal.
Thus, the reference anticipates the subject matter of claims 1-3, 5, 32-33, 47-48, 50, 53, 60, 88, 96, and 100.
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.
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 17 and 72 are rejected under 35 U.S.C. 103 as being unpatentable over Kerasioti et al. (Food Chemistry 155 (2014) 271-278) as evidenced by Tu et al. (J. Proteome Res. 2018, 17, 2963−2977) as applied to claims 1-3, 5, 32-33, 47-48, 50, 53, 60, 88, 96, and 100 above, and as evidenced by Rando et al. (The Journal of Cell Biology, Volume 125, Number 6, June 1994, 1275-1287).
Kerasioti as evidenced by Tu anticipates the subject matter of claims 1-3, 5, 32-33, 47-48, 50, 53, 60, 88, 96, and 100, and thus, also render them obvious.
Regarding claims 17 and 72, Kerasioti teaches the cells are mouse cells. Kerasioti does not teach wherein the cells are human cells. However, it is well-known in the art that mouse models are used for modeling human cells, as evidenced by Rando. Rando teaches cell-mediated gene therapy using primary myoblasts can be broadly applied to mouse models of human muscle and non-muscle diseases (Abstract).
Therefore, it would have been obvious to one of ordinary skill in the art to apply the teachings of Kerasioti to human cells with a reasonable expectation of success because Rando teaches mouse models can broadly be applied to human cells. One would be motivated to apply the teachings of Kerasioti to human cells because one would want to confirm the results when utilizing mouse cells such as proliferation, viability, and/or cellular response are consistent in human cells as compared to the mouse cell model.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Claims 39, 54, 56, and 94 are rejected under 35 U.S.C. 103 as being unpatentable over Kerasioti et al. (Food Chemistry 155 (2014) 271-278) as evidenced by Tu et al. (J. Proteome Res. 2018, 17, 2963−2977) as applied to claims 1-3, 5, 32-33, 47-48, 50, 53, 60, 88, 96, and 100 above, and further in view of Francis et al. (J Dairy Sci 78:1209-1218, 1995).
Kerasioti as evidenced by Tu anticipates the subject matter of claims 1-3, 5, 32-33, 47-48, 50, 53, 60, 88, 96, and 100, and thus, also render them obvious.
Regarding claim 39, as indicated in the 112(b) rejection above, this claim is interpreted as a method of obtaining whey from a milk product prior to cellular contact.
Regarding claims 39 and 94, Kerasioti teaches culturing cells with a culture medium comprising whey, however, is silent to the method of obtaining the whey from the milk product.
However, Francis teaches whey was investigated as a source of growth-stimulating factors that might replace or supplement fetal bovine serum in cell culture (Abstract). Francis teaches extracts comprising only 1 to 2% of whey protein displayed substantial growth-promoting activities on Balb/c 3T3 cells, L6 myoblasts, and human skin fibroblasts (Abstract). Francis teaches a method wherein the protein was eluted from preclarified whey (milk product) with a solution containing 400mM NaCl and 10 mM sodium citrate at pH 6.5, followed by elution of a second fraction with 1 M NaCl containing 250 mM NH4OH at pH 11 (p. 1210, 2nd column). Francis teaches the rat myoblasts were cultured in a medium comprising whey samples diluted with Dulbecco’s PBS to measure protein synthesis (p. 1210, 2nd column). Francis teaches the 400 mM NaCl eluate produced higher growth rates on a protein basis in Balb/c 3T3 cells, L6
myoblasts, and human skin fibroblasts (Fig. 4 and p. 1213, 1st column). Francis teaches this fraction induced cell growth with higher potency than FBS in the myoblasts and was 5 to 20 fold more potent than FBS in the other two cell lines (p. 1213, 1st column).
Therefore, it would have been obvious to one of ordinary skill in the art to have precipitated the whey protein from the milk product comprising adding a salt solution which comprises sodium chloride (NaCl) at a concentration of between 50 mM and 2.5 M with a reasonable expectation of success because Francis demonstrated multiple methods of extracting whey using various concentrations of NaCl. One would be motivated to have precipitated the whey protein from the milk product comprising adding a salt solution which comprises sodium chloride (NaCl) at a concentration of between 50 mM and 2.5 M because Francis teaches culturing cells with whey extracted with a solution comprising 400 mM NaCl increased cell growth in culture.
Regarding claim 54, Kerasioti teaches C2C12 cells were seeded in 25 cm2 or 75 cm2 culture flasks and incubated for 24 h at 37 °C in 5% CO2, then the medium was removed and replaced with a medium comprising sheep whey protein at different concentrations, 0-6.24 mg of protein/ml (Section 2.9). The instant specification in Example 1, discloses the whey powder was suspended in DMEM at different concentrations and gives examples of 2%, 1%, and 0.5% w/v. Therefore, it is understood that 2% by mass would be converted to 20mg/ml and 0.5% would be converted to 5mg/ml. Therefore, Kerasioti teaches whey protein concentrations of between 0.5 and 2% by mass.
Kerasioti teaches the second medium is a serum-free medium, thus, does not teach the second medium comprises FBS.
However, Francis teaches whey can be used to replace or supplement FBS in cell culture (Abstract).
Therefore, it would have been obvious to one of ordinary skill in the art to include FBS in the second medium with a reasonable expectation of success because if the intended purpose of the cell culture is cellular growth, FBS is well known in the art to contribute to cell growth in cell culture medium and Kerasioti was conducting viability assays to test the effects of whey concentrations in media, not cellular growth assays. Thus, the addition of FBS in a cell growth assay would be considered obvious. One would have been motivated to include FBS in the second medium because Francis teaches FBS can supplement whey in cell culture.
Regarding claim 56, Kerasioti does not teach wherein the second media comprises growth factor.
However, Francis teaches whey comprises several mitogenic growth factors (p. 1216, Discussion). Additionally, FBS is known to comprise insulin growth factor 1 and 2 as evidenced by Tu (Abstract). Thus, the second media as taught by Kerasioti in view of Francis comprises FBS.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NICHOLAS A. HUMPHRIES whose telephone number is (703)756-5556. The examiner can normally be reached Monday - Friday, 7:30am - 4:30 pm.
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.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Schultz can be reached at 571-272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/N.A.H./Examiner, Art Unit 1631
/LAURA SCHUBERG/Primary Examiner, Art Unit 1631
