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
The instant application is a national stage entry of PCT application PCT/GB2022/051808, filed 01/10/2024 under 35 USC 371. Acknowledgment is made of applicant's claim for foreign priority based on an application GB2110036.7 filed in United Kingdom of Britian and Northern Ireland on 07/12/2021.
Election/Restrictions
Applicant’s election without traverse of claims 1-3 and 6-12 in the reply filed on 06/30/2026 is acknowledged. Accordingly, claims 1-3 and 6-12 have been considered on the merits. Claims 4-5 and 13-18 are withdrawn from consideration pursuant 37 CFR 1.142(b).
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. See line 4 on page 25. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claims 1, 2 are 6 are objected to because of the following informalities:
Claim 1 recites multiple abbreviations such as PVP40, PEG8, PVP360 and PEG35. Abbreviations should be spelled out at the first encounter in the claims.
Claims 1, 2 and 6 recite "the group consisting of… or..." in the Markush group, the word "or" needs to be replaced with "and". Claim language defined by a Markush grouping requires selection from a closed group "consisting of" the alternative members. Id. at 1280, 67 USPQ2d at 1196. See also Amgen Inc. V. Amneal Pharmaceuticals LLC, 945 F.3d 1368, 1376-78, 2020 USPQ2d 3197 (Fed. Cir. 2020). Treatment of claims reciting alternatives is not governed by the particular format used (e.g., alternatives may be set forth as "a material selected from the group consisting of A, B, and C" or "wherein the material is A, B, or C"). See, e.g., the Supplementary Examination Guidelines for Determining Compliance with 35 U.S.C. 112 and for Treatment of Related Issues in Patent Applications ("Supplementary Guidelines"), 76 Fed. Reg. 7162 (February 9, 2011). See MPEP 2117.I.
Appropriate correction is required.
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, 3 and 6-12 are rejected under 35 USC 101 because the claimed invention is directed to non-statutory subject matter.
Instant claim 1 do not fall within at least one of the four categories of patent eligible subject matter because they are directed to a use of serum-free or reduced-serum cell culture medium comprising a basal medium and one or more macromolecular crowding agents for in vitro cell culture. The claimed recitation of a use, without setting forth any steps involved in the process, results in an improper definition of a process, i.e. results in a claim which is not a proper process under 35 U.S.C. 101. See for example Ex parte Dunki, 153 USPQ678 (Bd.App.1967) and Clinical Products, Ltd. V. Brenner, 255 F. Supp. 131, 149 USPQ 475 (D.D.C.1966).
Claims 3 and 6-12 depend from claim 1, and thus inherit the deficiency and are rejected on the same basis.
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 1-3 and 6-12 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.
Claim 1 is directed to a use of serum-free or reduced-serum cell culture medium comprising a basal medium and one or more macromolecular crowding agents for in vitro cell culture. The claim is provided for the use of serum-free or reduced-serum cell culture medium, but, since the claim does not set forth any steps involved in the method/process, it is unclear what method/process applicant is intending to encompass. A claim is indefinite where it merely recites a use without any active, positive steps delimiting how this use is actually practiced.
Claims 3 and 6-12 depend from claim 1, and thus inherit the deficiency and are rejected on the same basis.
Claims 1-3 contain the trademark/trade names Ficoll® 70 and Ficoll® 400. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade names are used to identify/describe a macromolecular crowding agent and, accordingly, the identification/description is indefinite.
Claims 6-12 depend from claim 1 or claim 2, and thus inherit the deficiency and are rejected on the same basis.
Claim Interpretation
As stated above, claim 1 is directed to a “use” of serum-free or reduced-serum cell culture medium comprising a basal medium and one or more macromolecular crowding agents for in vitro cell culture without active steps. In the interest of compacted prosecution, claim 1 is treated as the same method as recited in claim 2.
Instant claims recite “muscle cells” and “fat cells”. The specification provides the definition of “muscle cells”: the term "muscle cell" or "myocyte" encompasses precursor cells that differentiate into the three different muscle cell types. In other words, these terms encompass myoblast cells, as well as cardiac, skeletal and smooth muscle myocytes (p27, L36-37 and p28, L1-2). The term "fat
cell" or "adipocyte" encompasses precursor cells that differentiate into adipocytes. In other words, these terms encompass pre-adipocyte cells as well as adipocyte cells per se (p28, L10-12). The claims are interpreted in light of the definitions in the specification.
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 1-2 and 8 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Zeugolis et al. (EP 2532736 A1, cited in IDS).
Zeugolis et al. teach the production of tissue films or cell matrices, which can be used
as a living tissue substitute or an artificial tissue construct in tissue repair or replacement (Abstract).
Regarding claims 1 and 2, Zeugolis et al. teach a method for the production of a tissue substitute comprising culturing cells in the presence of macromolecular crowders, wherein the macromolecular crowders are large poly-dispersed macromolecules (parag 0020). The large poly-dispersed macromolecules may be selected from the group comprising carrageenan, dextran
sulphate and polysodium-1-styrene sulphonate (parag 0021). The cells may be selected from lung fibroblasts, dermal fibroblasts and human umbilical arteries smooth muscle cells (parag 0022). Zeugolis et al. teach in Example, human umbilical arterial smooth muscle cells are seeded and were allowed to attach for 24 hours. After 24 hours the medium was changed with medium containing macromolecular crowders (100Pg/ml dextran sulphate 500 kDa; 37.5mg/ml Ficoll™70 and 25mg/ml Ficoll™400; 100Pg/ml Polysodium-4-Styrenesulfonate, 75Pg/ml carrageenan and 100Pl/ml sepharose-CL) and with various percentages of FBS (0%, 0.5%, 1%, 2%, 5%, and 10%) (parag 0028). The method of culturing the human umbilical arterial smooth muscle cells with macromolecular crowders including Ficoll™70, Ficoll™400 and carrageenan, and with 0% FBS anticipates the use of a serum-free culture medium for culturing muscle cell as recited in claim 1 and the in vitro serum-free cell culture method as recited in claim 2.
Regarding claim 8, following the discussion above, Zeugolis et al. teach the medium with 0% FBS in the cell culture of human umbilical arterial smooth muscle cells (see parag 0028), that culture medium is a serum-free culture medium.
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.
Claims 1-3, 7-9 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Winter et al. (Mol Hum Reprod. 2020 Jul 1;26(7):498-509) in view of Nadeem et al. (J Cell Mol Med. 2021 Jul;25(14):6773-6785, published in June 2021).
Winter et al. utilized macromolecular crowding to recapitulate the levels of macromolecules in the in vivo environment of myometrial smooth muscle cells (p499, right column).
Regarding claims 1 and 2, Winter et al. teach culturing immortalized myometrial smooth muscle cells, hTERT-HM cells in conjunction with macromolecular crowders Ficoll 70 and Ficoll 400, together with ascorbic acid (p499, right column). Winter et al. also teach culture of hTERT-HM cells (see p500, left column, “Myometrial cell cultures” part), hTERT-HM cells were routinely cultured at 37°C, 5% CO2 in DMEM-F12 with 10% foetal calf serum (FCS) and 1% penicillin streptomycin (PS) until 80% confluent. Cells were then seeded into six-well plates or chamber slides at a density of 70 000 cells/cm2 in DMEM-F12 with 10% FCS. After 16 h, media were changed to either DMEM-F12 with 0.5% FCS (control media: C), DMEM/F12 and 0.5% FCS together with 100 mM L-ascorbic acid 2-phosphate (ascorbic media: A), or DMEM/F12, 0.5% FCS and 100 mM L-ascorbic acid 2-phosphate in combination with 37.5 mg/ml Ficoll 70 and 25 mg/ml Ficoll 400 (Ficoll/ascorbic media: F). This teaching reads on culturing muscle cell with reduced serum (0.5% FCS vs. 10% FCS) and using macromolecular crowding agents Ficoll 70 and Ficoll 400 (see group F).
Instant claims differ from Winter et al. that instant claims use serum-free or reduced-serum medium which has a maximum of 0.1% (v/v) serum in the cell culture medium. However, this was disclosed by Nadeem et al. at the time of instant invention.
Nadeem et al. examined the myometrial expression of 20α-HSD in pregnant women and mice, in association with term and preterm labour and determined whether it is affected by pro-inflammatory
stimuli and by the activity of NF-kB or AP-1TFs (p6774, right column).
Regarding claim 1, Nadeem et al. teach hTERT-HM cells can be cultured in serum-free medium (supplemented with 1% insulin selenium transferase)(see p6775, right column).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Winter et al.’s culture of hTERT-HM cells using macromolecular crowders Ficoll 70 and Ficoll 400 and reduced-serum medium (i.e., 0.5% FCS), and use serum-free culture medium as taught by Nadeem et al.. The only difference between instant claims and Winter et al.’s culture of hTERT-HM cells is instant claims use even less serum (0.1% serum v.s. 0.5% serum) or serum-free culture medium. Given that Winter et al. teach using much less serum (0.5% FSC compare to 10% FCS, see p500, left column) when adding macromolecular crowders Ficoll 70 and Ficoll 400 in the medium, and Nadeem et al. teach that hTERT-HM cells can be cultured in serum-free medium (supplemented with 1% insulin selenium transferase)(see p6775, right column), one of ordinary skill in the art would have substituted Winter et al.’s culture of hTERT-HM cells using reduced-serum medium (i.e., 0.5% FCS), and use serum-free medium as taught by Nadeem et al. depends on their research preference. This simple substitution of one known element (serum-free culture medium for hTERT-HM cells) for another known element (reduced serum (i.e., 0.5% serum) culture medium for hTERT-HM cells) is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (see MPEP § 2143, B.).
Regarding claim 3, Winter et al. teach culturing immortalized myometrial smooth muscle cells, hTERT-HM cells using DMEM/F12, 0.5% FCS and 100 mM L-ascorbic acid 2-phosphate in combination with 37.5 mg/ml Ficoll 70 and 25 mg/ml Ficoll 400 (p500, left column).
Regarding claim 7, following the discussion above, Winter et al. teach culturing immortalized myometrial smooth muscle cells, hTERT-HM cells using DMEM/F12, 0.5% FCS and 100 mM L-ascorbic acid 2-phosphate in combination with 37.5 mg/ml Ficoll 70 and 25 mg/ml Ficoll 400 (p500, left column). This teaching reads on that the basal medium is DMEM/F12.
Regarding claims 8 and 9, following the discussion above, Nadeem et al. teach hTERT-HM cells can be cultured in serum-free medium (supplemented with 1% insulin selenium transferase)(see p6775, right column). Herein the medium is a chemically defined serum-free cell culture medium.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Winter et al.’s culture of hTERT-HM cells using macromolecular crowders Ficoll 70 and Ficoll 400 and reduced-serum medium (i.e., 0.5% FCS), and use serum-free culture medium (supplemented with 1% insulin selenium transferase, which is a serum-free chemically defined culture medium) as taught by Nadeem et al.. The only difference between instant claims and Winter et al.’s culture of hTERT-HM cells is instant claims use even less serum (0.1% serum v.s. 0.5% serum) or serum-free culture medium. Given that Winter et al. teach using much less serum (0.5% FSC compare to 10% FCS, see p500, left column) when adding macromolecular crowders Ficoll 70 and Ficoll 400 in the medium, and Nadeem et al. teach that hTERT-HM cells can be cultured in serum-free chemically defined medium (supplemented with 1% insulin selenium transferase), one of ordinary skill in the art would have substituted Winter et al.’s culture of hTERT-HM cells using reduced-serum medium (i.e., 0.5% FCS), and use serum-free chemically defined medium as taught by Nadeem et al. depends on their research preference. This simple substitution of one known element (serum-free chemically defined culture medium for hTERT-HM cells) for another known element (reduced serum (i.e., 0.5% serum) culture medium for hTERT-HM cells) is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (see MPEP § 2143, B.).
Regarding claim 12, Winter et al. teach using 1% penicillin streptomycin (PS) in the culture medium (p500, left column).
Claims 1-3 and 7-12 are rejected under 35 U.S.C. 103 as being unpatentable over Winter et al. (Mol Hum Reprod. 2020 Jul 1;26(7):498-509) in view of Nadeem et al. (J Cell Mol Med. 2021 Jul;25(14):6773-6785, published in June 2021), as applied to claims 1-3, 7-9 and 12 above, further in view of Kent (Cell Culture Basics, published in 2016) and Domogauer et al. (Cell Commun Signal. 2021 Feb 26;19(1):30, published in February 2021).
The teaching of Winter et al. and Nadeem et al. is set forth above.
Regarding claims 10 and 11, Winter et al. and Nadeem et al. do not teach using glutamine, more specifically, 1-10 mM L-alanyl-L-glutamine dipeptide in the medium. However, this was disclosed by Kent and Domogauer et al. at the time of instant invention.
Kent teaches cell stem cell culture mediums, also disclose the common supplements to the basal culture medium (see p1, Introduction).
Domogauer et al. teach coculture of normal human fibroblasts of skin or lung origin with
various human cancer cell types using permeable microporous membrane inserts (Abstract).
Regarding claims 10 and 11, Kent teaches adding of glutamine, especially L-alanyl-L-glutamine dipeptide in the culture medium: L-glutamine is an essential amino acid that is a required additive to most cell culture media, facilitating the storage and transfer of nitrogen to the cells in culture. L-glutamine is quite unstable, should be added to freshly prepared media just prior to use. L-alanyl-L-glutamine dipeptide is stable in cell culture medium over longer periods of time (p3, “Glutamine” part). Domogauer et al. teach adding 2 mM L-alanyl-L-glutamine in the culture medium for in vitro cell culture (p3, left column).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Winter et al. in view of Nadeem et al.’s culture of hTERT-HM cells using macromolecular crowders Ficoll 70 and Ficoll 400 and serum-free medium, and adds glutamine or specifically L-alanyl-L-glutamine dipeptide (i.e., in the concentration of 2 mM) in the culture medium as taught by Kent and Domogauer et al.. The skilled artisan would have been motivated to add glutamine or L-alanyl-L-glutamine dipeptide in the culture medium since kent teaches L-glutamine is an essential amino acid that is a required additive to most cell culture media, facilitating the storage and transfer of nitrogen to the cells in culture, which is benefit for the cell growth. There would be a reasonable expectation of success of adding glutamine or L-alanyl-L-glutamine dipeptide (i.e., in the concentration of 2 mM) in the culture medium since there are commercially available L-alanyl-L-glutamine dipeptide as supplement of the basal culture medium and Domogauer et al. teach the final concentration of L-alanyl-L-glutamine dipeptide in the culture medium (see p3, left column).
Claims 1-2 and 6-9 are rejected under 35 U.S.C. 103 as being unpatentable over Pandurangan et al. (Appl Microbiol Biotechnol. 2014 Sep;98(17):7359-64) in view of Tsiapalis et al. (Biomaterials. 2021 Aug;275:120943, cited in IDS).
Pandurangan et al. teach co-culture system to study fat and muscle cells (see Abstract).
Regarding claims 1, 2 and 6, Pandurangan et al. teach serum-free medium is required for co-culture to identify growth factors and hormones. A defined medium called ITT consisting 500 nM insulin, 0.2 nM thyroid hormone, and 10 μg/ml transferrin within a basal medium of 1:1 Dulbecco's modified Eagle’ s medium (DMEM) and Ham’s F-12 medium for culture of human preadipocytes. ITT medium promotes substantial fusion of satellite cell strains. Therefore, it appears as an appropriate medium that could support preadipocyte and satellite cell viability. ITT is used in the 3T3-L1 preadipocyte and satellite
cell strain co-culture experiments (p7361, left column). This medium could be modified by addition of 100 ng/ml fibroblast growth factor (FGF), 50 ng/ml corticosterone, and a higher level of insulin (4.7 μg/ml) and seems to be an appropriate medium for the co-culture of fat and muscle cells (p7361, left column). Pandurangan et al. do not teach using one or more macromolecular crowding agents including PEG8, PEG35,PVP40, PVP360 or carrageenan in the co-culture. However, this was disclosed by Tsiapalis et al. at the time of instant invention.
Tsiapalis et al. teach the concept of macromolecular crowding is discussed in both intracellular and extracellular context. Particular emphasis is given on how the physicochemical properties of the crowding molecules govern and determine kinetics, equilibria and mechanism of action of biochemical and biological reactions, processes and functions (Abstract).
Regarding claims 1, 2 and 6, Tsiapalis et al. teach use of macromolecular crowding (MMC) in eukaryotic cell culture (see, i.e., Table 4), as well as the function of macromolecular crowding agents, for instance, MMC has been utilized to drive stem cell differentiation and to develop tissue-derived matrices for effective cell expansion in vitro. In addition to having the capacity to develop functional cellular products, MMC can also significantly improve the efficiency of processes. MMC can be used as quality control tool to assess the effectiveness of media to induce a specific phenotype, as has been shown before for chondrogenic media (p2, right column). Tsiapalis et al. further teach specific MMCs such as dextran sulphate 500 kDa has been shown to induced myofibroblast trans-differentiation in human corneal fibroblast cultures, carrageenan and the Ficoll 70 KDa/Ficoll 400 KDa cocktail have been shown to sustain their physiological protein and gene expression (p11, left column). In stem cell cultures, the sulphated carrageenan, galactofucan and fucoidan have been shown to enhance chondrogenesis and osteogenesis and to not affect or even decrease adipogenesis, the non-sulphated Ficoll 70 KDa/Ficoll 400 KDa cocktail to enhance adipogenic differentiation (p11, right column). Moreover, the Ficoll cocktail has been shown to enhance heparin sulphate proteoglycan deposition, which sequesters a variety of growth factors, including fibroblast growth factor, that is a potent adipogenic inducer (p11, right column-p12, left column).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Pandurangan et al.’s co-culture of fat of muscles using serum-free chemically defined ITT medium, and add MMC such as dextran sulphate, carrageenan or Ficoll70/Ficoll 400 in the medium as taught by Tsiapalis et al.. The skilled artisan would have been motivated to add MMC to ITT medium since Tsiapalis et al. teach MMCs such as dextran sulphate, carrageenan or Ficoll70/Ficoll 400 is benefit to in vitro cell culture, i.e., drive stem cell differentiation and to develop tissue-derived matrices for effective cell expansion in vitro, as well as promote growth factors for the cell growth and differentiation. There would be a reasonable expectation of success of adding MMCs such as dextran sulphate, carrageenan or Ficoll70/Ficoll 400 to the ITT medium since Tsiapalis et al. teach examples of using MMCs in the cell culture medium (i.e., Table 4).
Regarding claims 7-9, following the discussion above, Pandurangan et al. teach serum-free medium is required for co-culture to identify growth factors and hormones. A defined medium called ITT consisting 500 nM insulin, 0.2 nM thyroid hormone, and 10 μg/ml transferrin within a basal medium of 1:1 Dulbecco's modified Eagle’ s medium (DMEM) and Ham’s F-12 medium for culture of human preadipocytes (p7361, left column). This teaching reads on that the basal medium is DMEM/F12, and it is a chemically defined serum-free culture medium.
Claims 1-2 and 6-12 are rejected under 35 U.S.C. 103 as being unpatentable over Pandurangan et al. (Appl Microbiol Biotechnol. 2014 Sep;98(17):7359-64) in view of Tsiapalis et al. (Biomaterials. 2021 Aug;275:120943, cited in IDS), as applied to claims 1-2 and 6-9 above, further in view of Kent (Cell Culture Basics, published in 2016) and Domogauer et al. (Cell Commun Signal. 2021 Feb 26;19(1):30).
The teaching of Pandurangan et al. and Tsiapalis et al. is set forth above.
Regarding claims 10 and 11, Pandurangan et al. and Tsiapalis et al. do not teach using glutamine, more specifically, 1-10 mM L-alanyl-L-glutamine dipeptide in the medium. However, this was disclosed by Kent and Domogauer et al. at the time of instant invention.
Kent teaches cell stem cell culture mediums, also disclose the common supplements to the basal culture medium (see p1, Introduction).
Domogauer et al. teach coculture of normal human fibroblasts of skin or lung origin with
various human cancer cell types using permeable microporous membrane inserts (Abstract).
Regarding claims 10 and 11, Kent teaches adding of glutamine, especially L-alanyl-L-glutamine dipeptide in the culture medium: L-glutamine is an essential amino acid that is a required additive to most cell culture media, facilitating the storage and transfer of nitrogen to the cells in culture. L-glutamine is quite unstable, should be added to freshly prepared media just prior to use. L-alanyl-L-glutamine dipeptide is stable in cell culture medium over longer periods of time (p3, “Glutamine” part). Domogauer et al. teach adding 2 mM L-alanyl-L-glutamine in the culture medium for in vitro cell culture (p3, left column).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Pandurangan et al.’s serum-free ITT culture medium, and adds glutamine or specifically L-alanyl-L-glutamine dipeptide (i.e., in the concentration of 2 mM) in the culture medium as taught by Kent and Domogauer et al.. The skilled artisan would have been motivated to add glutamine or L-alanyl-L-glutamine dipeptide in the culture medium since kent teaches L-glutamine is an essential amino acid that is a required additive to most cell culture media, facilitating the storage and transfer of nitrogen to the cells in culture, which is benefit for the cell culture. There would be a reasonable expectation of success of adding glutamine or L-alanyl-L-glutamine dipeptide (i.e., in the concentration of 2 mM) in the culture medium since there are commercially available L-alanyl-L-glutamine dipeptide as supplement of the basal culture medium and Domogauer et al. teach the final concentration of L-alanyl-L-glutamine dipeptide in the culture medium (see p3, left column).
Regarding claim 12, Pandurangan et al. and Tsiapalis et al. do not teach adding penicillin and streptomycin in the culture medium. However, Domogauer et al. teach adding penicillin and streptomycin in culture medium (p3, left column).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Pandurangan et al.’s serum-free ITT culture medium, and adds penicillin and streptomycin in the culture medium as taught by Domogauer et al.. The skilled artisan would have been motivated to add penicillin and streptomycin in the culture medium to prevent microbial contamination since Domogauer et al. use penicillin and streptomycin in different culture medium for culturing different cell line (see p3, left column). There would be a reasonable expectation of success of adding penicillin and streptomycin in the culture medium since Domogauer et al. teach the concentration of penicillin and streptomycin in the culture medium (p3, left column).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
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Claims 1-3 and 6-12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-12 of copending Application No. 18/578, 286 in view of Tsiapalis et al. (Biomaterials. 2021 Aug;275:120943), because the co-pending claims render obvious the instant claims.
This is a provisional nonstatutory double patenting rejection.
Regarding instant claims 1-3 and 6, co-pending claims 1-6 teach use of a serum-free or reduced-serum cell culture medium comprising a basal medium and one or more macromolecular crowding agents for in vitro cell culture skin cells or corneal cells, and in vitro culturing skin cells or corneal cells in a serum-free or reduced-serum cell culture medium comprising a basal medium and one or more macromolecular crowding agents, wherein the macromolecular crowding agent is selected from the group consisting of: PEG8, PEG35, PVP40, and PVP360; or a combination thereof. Co-pending claims do not teach the cells are muscle cells or fat cells. However, this was disclosed by Tsiapalis et al..
Tsiapalis et al. teach the concept of macromolecular crowding is discussed in both intracellular and extracellular context. Particular emphasis is given on how the physicochemical properties of the crowding molecules govern and determine kinetics, equilibria and mechanism of action of biochemical and biological reactions, processes and functions (Abstract).
Regarding claims 1-3 and 6, Tsiapalis et al. teach use of macromolecular crowding (MMC) in eukaryotic cell culture (see, i.e., Table 4), that MMCs can be used in different cell types such as skin fibroblasts, corneal fibroblasts, pig vascular smooth muscle cells, adipose derived stem cells (see Table 4).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify co-pending claims’ method of using macromolecular crowding agents for culturing skin cells or corneal cells, and use the same method and culture medium for culturing muscle cells or adipose cells as taught by Tsiapalis et al.. The only difference between instant claims and co-pending claims’ method of culturing skin cells or corneal cells is instant claims are culturing muscle cells or adipose cells using the same method and culture medium. Given Tsiapalis et al. teach MMCs can be used in different cell types including skin fibroblasts, corneal fibroblasts, pig vascular smooth muscle cells, adipose derived stem cells (Table 4), one of ordinary skill in the art would have substituted culturing skin cells or corneal cells using the macromolecular crowding agents, and use the same method for culturing muscle cells or fat cells. This simple substitution of one known element (culturing muscle cells or fat cells using macromolecular crowding agents) for another known element (culturing skin cells or corneal cells using macromolecular crowding agents) is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (see MPEP § 2143, B.).
Regarding claim 6-12, co-pending claims 7-12 disclose the same culture medium as recited in instant claims.
Conclusion
No claims are allowed.
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/Q.G./Examiner, Art Unit 1633
/FEREYDOUN G SAJJADI/Supervisory Patent Examiner, Art Unit 1699
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