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 1-13 are pending.
Objections to Abstract
The abstract is objected to because it uses the term “B27” (line 5) which is a trade name or mark used in commerce that is not accompanied by the generic terminology and does not include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Appropriate correction is Required.
Objections to the Specification
Trade Name or Marks used in Commerce
The use of the terms B27, DMEM, and Primocin, which are trade names or marks used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Objections to Specification
The disclosure is objected to because of the following informalities:
Pg. 16 has the following figure embedded into the specification:
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(pg. 16).
Drawings must be presented on one or more separate sheets. They may not be included in the description, the claims or the abstract (see MPEP 1825 and 37 CFR 1.437)
Appropriate correction is required.
Claim Objections
Claims 1, 7-8 and 12-13 are objected to because of the following informalities:
Claims 1 and 7-8 recite “ROCK kinase inhibitor,” however, in the art, “ROCK” is known to stand for “rho-associated protein kinase” and therefore the claimed phrase “ROCK kinase inhibitor,” includes “kinase” twice and is unnecessarily redundant.
Claim 12 recites “culturing by using the primary cell culture medium of step (1).” Because methods of culturing using cell culture mediums area known in the art, the scope is clear. However, to improve the clarity and readability of the claim, it is recommended that Applicant amend to “culturing with the primary cell culture medium of step (1).”
Claim 12 recites enumerated steps with step (3) reciting “(3) inoculating primary lung cancer epithelial cells isolated from lung cancer tissues in the culture vessel which is coated with extracellular matrix gel, and culturing by using the primary cell culture medium of step (1).” Because this includes two steps, it is recommended that Applicant enumerate the last step as (4). To be consistent with the recommendation above, it is recommended that Applicant amend to “(4) culturing with the primary cell culture medium of step (1)” to improve the readability of the claim.
Claim 13 recites “characterized in that, comprising” which includes two transitional phrases. Because the MPEP states that the transitional term "comprising", is synonymous with "including," "containing," or "characterized by," the scope of the claim is clear since both the recited transitional phrases are open-ended (see MPEP 2111.03 (I)). However, it is unnecessarily redundant to include two synonymous transitional phrases and it is recommended that Applicant amend to one transitional phrase to improve the readability of the claim.
Claim 13 recites enumerated steps with step (3) reciting “adding the drug which has been diluted to gradients to the lung cancer epithelial cells obtained in step (1), and detecting the cell viability.” Because this includes two steps, it is recommended that Applicant enumerate the last step as “(4) detecting the cell viability” to improve the readability of the claim.
Appropriate correction is required.
Claim Rejections - 35 USC § 112 (b)
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 1-13 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.
Claims 1 and 7 recite the trademarked term “B27,” and claim 9 recites the trademarked terms “DMEM/F12” (which included the trademarked term DMEM), “DMEM” and “Primocin”.
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 name is used to identify/describe cell culture additive and, accordingly, the identification/description is indefinite.
Because this reagent was developed by the manufacturer at the time of the applicant’s invention under the trade names and as a result is proprietary, which means what constitutes as B27, DMEM, or Primocin can change, and these changes do not need to be disclosed by these companies to the public. Accordingly, the identification of the trade name is indefinite and the applicant is advised to employ a sequence, the SeqID, IUPAC name and/or CAS number for this agent.
MPEP 2173.05(u) states that if 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 the 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). See also Eli Lilly & Co. v. Apotex, Inc., 837 Fed. Appx. 780, 784-85, 2020 USPQ2d 11531 (Fed. Cir. 2020).
Regarding the status of B27 and DMEM as trademarks, Applicant is directed to MPEP 608.01(v) which defines a trademark as follows:
The term "trademark" includes any word, name, symbol, or device, or any combination thereof-
(1) used by a person, or
(2) which a person has a bona fide intention to use in commerce and applies to register on the principal register established by this chapter,
to identify and distinguish his or her goods, including a unique product, from those manufactured or sold by others and to indicate the source of the goods, even if that source is unknown.
Although the Trademarks for DMEM (number 98618988) and B27 (number 77129891) were abandoned, they still meet the definition of a trademark according to the MPEP because they are each a term “which a person has a bona fide intention to use in commerce” “to identify and distinguish his or her goods.” Since the trademark Application was filed (i.e. “applies to register on the principal register” MPEP 608.01(v) above), it falls under the definition of a trademark, even if the Trademark Status is now Dead/Abandoned.
Accordingly, for the reasons stated above, the claims are indefinite due to the presence of the trademark terms.
By nature of their ultimate dependency on claim 1, claims 2-13 are also rejected because they do no clarify the issue.
Claims 6-7 recite preferential language (“preferably”). If stated in the claims, examples and preferences may lead to confusion over the intended scope of a claim (see MPEP 2173.05(d). Therefore, it is unclear which aspect(s) of the claim is/are intended to be within the scope(s) of the claim(s) (see also MPEP 2173.05(b)).
Claim 8 recites “the MST1/2 kinase inhibitor is Compound 1.” However, claim 1, upon which claim depends, does not recite “Compound 1.” Therefore, there is improper antecedent basis for this term and the metes and bounds of the claim are unclear because it is unclear what the scope of the required claim element of “compound 1” encompasses.
Claim 9 recites the term “initial medium,” while the instant specification is silent to a definition of the phrase “initial medium.” The scope of claim 9 is indefinite because the term “initial” suggests a timing, while the claim is drawn to a single medium. The metes and bounds of the structure of the claims is indefinite because it is unclear whether the mediums recited in claim 9 are required at a particular timing and it is unclear how that structure would be incorporated into the composition of instant claims.
Claim 10 recites “free of serum, bovine pituitary extract, Wnt agonists, R-spondin family proteins, BMP inhibitors, nicotinamide, or N-acetylcysteine” which is a negative limitation together with a list of alternative embodiments. The presence of negative limitation together with a list of alternative embodiments makes it unclear whether the negative limitation applies to all of the listed options, or whether it applies to the listed options in the alternative.
Claim 11 recites the subjective terminology “normal” lung cancer epithelial cells while the specification is silent to a definition of “normal.”A claim may be rendered indefinite by reference to subjective terminology (see MPEP 2173.05(b), IV). Specifically, the term “normal” is a subjective term which renders the claim indefinite. The term is not defined by the claim, the specification does not provide a standard for some standard for measuring the scope of the term, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim 12 recites “preparing the primary cell culture medium,” which makes the scope of the claim unclear because it appears to require additional unrecited steps of preparing and therefore, because specific steps of preparing are not provided, this makes the scope of the claim unclear.
To overcome this rejection to claim 12, it is recommended that Applicant amends to “providing the primary cell culture medium of claim 1”.
By nature of its dependency on claim 12, claim 13 is also rejected because it does not clarify the issue.
Claim 13 recites the preamble of “a method for evaluating or screening a drug for treating lung cancer” and claim 13 recites the active method step of “detecting the cell viability” which appears to be the metric of the claimed method. The scope of the claimed method is indefinite because there is no nexus between the active method step of “detecting the cell viability” and the preamble of “evaluating or screening a drug for treating lung cancer.” In other words, the scope is unclear because it is unclear how the result of the cell viability detection relates to the evaluation or screen of a drug.
Claim 13 recites “(3) adding the drug which has been diluted to gradients to the lung cancer epithelial cells” which makes the scope of the claim indefinite because the configuration of the drug which has been diluted to gradients in unclear. Specifically, the step of “(3) adding the drug which has been diluted to gradients to the lung cancer epithelial cells” is indefinite because it is unclear whether all the gradients are added at once, or whether they are added to different samples of the lung cancer epithelial cells.
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.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Non-Statutory Double Patenting
Provisional Non-Statutory Double Patenting
U.S. Co-pending Application No. 18700796
Claims 1-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of co-pending application No. 18700796 (claim set filed 12th, April, 2024) in view of Zheng et al. (J Neurosci. 1997 Jan 1;17(1):216-26.; henceforth “Zheng”) and Zhang et al. (Cell Rep. 2018 Oct 16;25(3):598–610.e5.; see IDS filed 10th, October, 2025; henceforth “Zhang”).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented
The subject matter claimed in the instant application is disclosed in the referenced application as follows: the primary cell culture medium, culturing method, and screening method makes obvious the primary cell culture medium, culturing method, and screening method of instant application.
Although the claims at issue are not identical, they are not patentably distinct for the reasons stated below.
Regarding claim 1, U. S. Co-pending App ‘796 claims a cell culture media comprising an MST1/2 kinase inhibitor of Formula (I) with R1-R6 as claimed or a pharmaceutically acceptable salt, or a solvate thereof; at least one Rho kinase inhibitor selected from the group consisting of Y27632, fasudil, and H-1152; N2; B27; epidermal growth factor; transferrin (as insulin-transferrin-selenium supplement) and gastrin (claims 1-5).
However, regarding claim 1, although U. S. Co-pending App ‘796 claims the cell culture medium is for primary ovarian cancer cells, which includes epithelial cells, U. S. Co-pending App ‘796 does not claim the medium comprises a fibroblast growth factor.
Nevertheless, regarding claim 1, Zheng teaches a cell culture media for epithelial cells comprising a fibroblast growth factor of FGF7 (abstract; Materials and Methods pg. 217 col. 1) which stimulated proliferation (abstract; pg. 217 col. 1 2nd para.; pg. 219; Figure 2).
Therefore, regarding claim 1, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the cell culture media as claimed by U.S. Co-pending App ‘796 and combine the known prior art element of the FGF7 of Zheng to obtain the predicable result of a cell culture media for epithelial cells. One of ordinary skill would have been motivated to do so as taught by Zheng to stimulate proliferation of the cells (abstract; pg. 217 col. 1 2nd para.; pg. 219; Figure 2). Regarding the reasonable expectation of success, Zheng evidences preparation of cell culture media comprising FGFs (abstract; Materials and Methods pg. 217 col. 1).
However, regarding claim 1, although U. S. Co-pending App ‘796 claims the cell culture medium is for primary ovarian cancer cells, which includes epithelial cells, U. S. Co-pending App ‘796 does not claim the medium comprises a TGFβ type I receptor inhibitor selected from at least one of A83-01, SB43154 and Repsox.
Nevertheless, regarding claim 1, Zhang teaches including a TGFβ type I receptor inhibitor of A83-01, SB431542, Repsox in a cell culture media for epithelial cells to promote expansion (pg. 3 “Results” last para.; pg. 4 1st para.).
Therefore, regarding claim 1, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the cell culture media as claimed by U.S. Co-pending App ‘796 in view of Zheng, and combine the known prior art element of the TGFβ type I receptor inhibitor of A83-01, SB431542 or Repsox of Zhang to obtain the predictable result of a cell culture media for epithelial cells. One of ordinary skill would have been motivated to do so as taught by Zhang to promote proliferation and expansion of the cells (pg. 3 “Results” last para.; pg. 4 1st para.). Regarding the reasonable expectation of success, Zhang evidences preparation of a cell culture media comprising TGFβ type I receptor inhibitor of A83-01, SB431542 or Repsox (pg. 3 “Results” last para.; pg. 4 1st para. Methods).
Regarding claim 1, the preamble of for culturing primary lung cancer epithelial cells recites an intended use of the claimed composition. The primary cell culture media claimed by U.S. Co-pending App ‘796 in view of Zheng and Zhang comprises the structural components of instant claims and is therefore capable of meeting the intended use of culturing laryngeal cancer epithelial cells and meets instant claims.
Regarding claim 2, further to the discussion of claim 1 above, U.S. Co-pending App ‘796 claims
R1 is selected from Cl-C6 alkyl, C3-C6 cycloalkyl, C4-C8 cycloalkylalkyl, C2-C6 spirocycloalkyl, and phenyl optionally independently substituted with 1-2 R6, naphthyl optionally independently substituted with 1-2 R6, phenylmethyl optionally independently substituted with 1-2 R6 and thienyl optionally independently substituted with 1-2 R6;
R2 and R3 are each independently selected from C1-C3 alkyl;
R4 and R5 are each independently selected from hydrogen, C 1-C6 alkyl, C3-C6 cycloalkyl, C4-C8 cycloalkylalkyl, hydroxyl C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkylamino C1-C6 alkyl, C1-C6 alkoxy C1-C6 alkyl, piperidyl Cl-C6 alkyl, and tetrahydropyranyl Cl-C6 alkyl; and
R6 is selected from halogen, C1-C6 alkyl, C1-C6 alkoxy, and C1-C6 haloalkyl (claim 2).
Regarding claim 3, further to the discussion of claim 1 above, U.S. Co-pending App ‘796 claims the MST1/2 kinase inhibitor comprises a compound of Formula (Ia) or a pharmaceutically acceptable salt, or a solvate thereof,
wherein,
R1 is selected from C1-C6 alkyl, phenyl optionally independently substituted with 1-2 R6, thienyl optionally independently substituted with 1-2 R6, and phenylmethyl optionally independently substituted with 1-2 R6;
R5 is selected from hydrogen, C1-C6 alkyl, and C3-C6 cycloalkyl; and
R6 is independently selected from halogen, C1-C6 alkyl, and C1-C6 haloalkyl (claim 3).
Regarding claim 4, further to the discussion of claim 1 above, U.S. Co-pending App ‘796 claims
R1 is phenyl optionally independently substituted with 1-2 R6;
R5 is hydrogen; and
R6 is preferably fluoro, methyl or trifluoromethyl (claim 4).
Regarding claim 5, further to the discussion of claim 1 above, U.S. Co-pending App ‘796 claims MST1/2 kinase inhibitor comprises at least one compound from compounds 1-59 as claimed or a pharmaceutically acceptable salt thereof (claim 5).
Regarding claim 6, further to the discussion of claim 1 above, U.S. Co-pending App ‘796 claims the amount of the MST1/2 kinase inhibitor is 2.5 µM-20 µM (claim 6) which overlaps with the claimed range of 2.5-10 μM and thereby make it obvious.
Regarding claim 7, further to the discussion of claim 1 above, U.S. Co-pending App ‘796 claims the amount of the ROCK kinase inhibitor in the culture medium is 2.5 µM-20 µM (claim 6) which overlaps with the claimed range of 2.5-18 μM;
the volume concentration of the B27 additive or the N2 additive in the culture medium is 1:25 to 1:400 (claim 6) which overlaps with the claimed ranges of 2.5-18 μM 1:25-1:800 and 1:25-1:200;
the amount of the epidermal growth factor is 2.5 -40 ng/mL (claim 6) which overlaps with the claimed 2.5-80 ng/ml and 10-40 ng/ml. Because these ranges overlap with the instantly claimed ranges, they make the claimed ranges obvious.
Regarding claim 8, further to the discussion of claim 1 above, U.S. Co-pending App ‘796 claims
the MST1/2 kinase inhibitor is Compound 1 (claims 1-5);
the ROCK kinase inhibitor is Y27632 (claim 1);
and Zhang teaches and makes obvious above that the TGFβ type I receptor inhibitor is A83-01.
Regarding claim 9, further to the discussion of claim 1 above, U.S. Co-pending App ‘796 claims an initial medium selected from the group consisting of DMEM/F12, DMEM, F12 or RPMI-1640; and one or more antibiotics selected from the group consisting of streptomycin/penicillin, amphotericin B and Primocin (claim 7).
Regarding claim 10, further to the discussion of claim 1 above, U.S. Co-pending App ‘796 does not claim serum, bovine pituitary extract, Wnt agonists, R-spondin family proteins, BMP inhibitors, nicotinamide, or N-acetylcysteine and therefore it would be obvious not to include these in the preparation of the suggested media.
Regarding claim 11, further to the discussion of claim 1 above, as stated above (see claim 1 rejection above), the preamble of for culturing primary lung cancer epithelial cells recites an intended use of the claimed composition. The primary cell culture media claimed by U.S. Co-pending App ‘796 in view of Zheng and Zhang comprises the structural components of instant claims and is therefore capable of meeting the intended use of culturing the specific lung cancer cells, normal lung cancer epithelial cells, and lung cancer epithelial stem cells.
Regarding claims 12 and 13, further to the discussion of claim 1 above, U.S. Co-pending App ‘796 claims a method for culturing primary ovarian cancer cells, comprising the following steps: (1) preparing the culture medium for primary ovarian cancer cells of claims 1-7; (2) obtaining primary ovarian cancer cells from ovarian cancer tissue samples; (3) adding the culture medium for primary ovarian cancer cells obtained in step (1) to the primary ovarian cancer cells obtained in step (2) for culture (claims 8 and 10-15) and U.S. Co-pending App ‘796 claims a method for evaluating or screening a drug for treating ovarian cancer, characterized in that, comprising the following steps: (1) culturing primary ovarian cancer cells using the method for culturing primary ovarian cancer cells of claim 8; (2) selecting the drug to be tested and diluting the drug into desired concentration gradients; (3) adding the drug which has been diluted into various concentration gradients to the primary ovarian cancer cells cultured in step(1); (4) detecting the cell viability (claim 9).
However, regarding claims 12 and 13, U.S. Co-pending App ‘796 does not claim a method for culturing primary lung cancer epithelial cells (instant claim 12) and U.S. Co-pending App ‘796 does not claim a method for evaluating or screening a drug for treating lung cancer (instant claim 13).
Nevertheless , regarding claims 12-13, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to practice the methods of U.S. Co-pending App ‘796 and simply substitute the lung cancer epithelial cells, which are primary cancer epithelial cells for the ovarian cancer cells which include epithelial cells of U.S. Co-pending App ‘796 to obtain the predicable result of a method of culturing epithelial cancer cells for the reason of culturing cancer cells to screen drugs for treating lung cancer.
Since the instant application claims are obvious over cited application claims, in view of Zheng and Zhang, said claims are not patentably distinct.
Pertinent Co-Pending Applications
The following co-pending Applications are made of record because they are pertinent to Applicant’s disclosure but are not relied upon for a rejection.
U.S. Co-pending Application Nos 17918971, 17927530, 18577457 and 18690412 each claim cell culture medias comprising an MST1/2 kinase inhibitor identical to the instantly claimed Formula (I) as well as a method of culturing using the medium and a method of screening using the medium. Each of the claimed cell culture medias recites an intended use of a specific cell type.
U.S. Co-pending Application No. 17918971
U. S. Co-pending App ‘971 (claim set filed 25th, February, 2026) claims a cell culture media comprising an MST1/2 kinase inhibitor of Formula (I), a ROCK inhibitor, at least one additive selected from a B27 additive and an N2 additive, an epidermal growth factor, transferrin (as insulin-transferrin-selenium complex), a TGFβ type I receptor inhibitor selected from at least one of A83-01, SB431542, Repsox, SB505124, SB525334, SD208, LY36494, and SJN2511 (claim 1).
U. S. Co-pending App ‘971 does not claim the required elements of instant Application claims of fibroblast growth factor and gastrin in the cell culture media and these are not fairly taught or suggested by the prior art.
U.S. Co-pending Application No. 17927530
U. S. Co-pending App ‘530 (claim set filed 3rd, February, 2026) claims a cell culture media comprising an MST1/2 kinase inhibitor of Formula (I), a fibroblast growth factor (FGF7), transferrin (as insulin-transferrin-selenium complex), and a TGFβ type I receptor inhibitor selected from at least one of A83-O1, SB431542, Repsox, SB505124, SB525334, SD208, LY36494, or SJN251.
U. S. Co-pending App ‘530 does not claim the required elements of instant Application claims of a ROCK kinase inhibitor selected from at least one of Y27632, Fasudil, and H-1152; at least one additive selected from a B27 additive and an N2 additive; an epidermal growth factor and gastrin and these are not fairly taught or suggested by the prior art.
U.S. Co-pending Application No. 18577457
U. S. Co-pending App ‘457 (claim set filed 8th, January, 2024) claims a cell culture media comprising an MST1/2 kinase inhibitor of Formula (I), at least one ROCK inhibitor selected from the group consisting of Y27632, fasudil, and H-1152; a fibroblast growth factor (FGF7); at least one additive selected from the group consisting of B27 additive and N2 additive; and at least one TGFβ type I receptor inhibitor selected from the group consisting of A83-01, SB431542, Repsox, SB505124, SB525334, SD208, LY36494, and SJN2511.
U. S. Co-pending App ‘457 does not claim the required elements of instant Application claims of an epidermal growth factor; transferrin and gastrin and these are not fairly taught or suggested by the prior art.
U.S. Co-pending Application No. 18690412
U. S. Co-pending App ‘412 (claim set filed 8th, March, 2024) claims a cell culture media comprising an MST1/2 kinase inhibitor of Formula (I), a ROCK Inhibitor (Y27632), at least one cell culture additive selected from N2 and B27, an epidermal cell growth factor and transferrin (as ITS).
U. S. Co-pending App ‘457 does not claim the required elements of instant Application claims of a fibroblast growth factor, gastrin or a TGFβ type I receptor inhibitor selected from at least one of A83-01, SB431542, Repsox, SB505124, SB525334, SD208, L Y36494, and SJN2511 and these are not fairly taught or suggested by the prior art.
Pertinent Art
The following prior art made of record but not relied upon is considered pertinent to Applicant’s disclosure.
Triastuti
Triastuti et al. (Br J Pharmacol. 2019 Oct 8;176(20):3956–3971.; henceforth “Triastuti”) discloses a cell culture media comprising an MST1 kinase inhibitor (XMU-MP-1 cultured 72 hours with “the addition of XMU‐MP‐1 at 1–5 μM” pg. 3958 col. 1 3rd para.).
Liu
Liu et al. (WO-2020073906-A1; see IDS filed 10th October, 2025; henceforth “Liu”) discloses a pharmaceutical composition comprising an MST kinase inhibitor of the following structure:
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(abstract; claims;)
Which encompasses embodiments of the instantly claimed Markush structure of Formula (I), copied below for reference.
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(from instant claim 1).
The MST kinase inhibitor structure disclosed by Liu comprises the structure of Formula (I) of instant claim 1 where:
R1 (of instant claims, R4 of Liu reference) is selected from C1-C6 alkyl, C3-C6 cycloalkyl, C4-C8 cycloalkylalkyl, C2-C6 spirocycloalkyl, heteroaryl, or aryl (claims; pg. 1);
R2 and R3 (of instant claims, R2 and R3 of Liu reference) are each independently selected from Cl-C6 alkyl (claims);
R4 and R5 (of instant claims, R5 and R6 of Liu reference) are each independently selected from hydrogen, C1- C6 alkyl, C3-C6 cycloalkyl, C4-C8 cycloalkylalkyl, C3-C6 heterocycloalkyl, C1 -C6 alkylamino C1-C6 alkyl, C1-C6 alkoxy Cl-C6 alkyl, and C3-C6 heterocyclyl Cl-C6 alkyl (claims) (see also specifically recited structures in the tables which recite specific structures within the claimed Markush).
Liu discloses the composition comprises Ringer’s injection or lactated Ringer’s injection.
Liu2
Liu et al. (US-20230235283-A1; Published 17th, October 2024 with priority to 8th, July, 2021; henceforth “Liu2”) discloses a primary cell culture medium comprising an MST 1/2 Kinase Inhibitor of Formula I, ROCK inhibitor selected from the group consisting of Y27632, Fasudil, and H-1152, fibroblast growth factor (Tables 3 and 5), and
B27 additive and/or N2 additive (para. [0019]);
an epidermal growth factor (EGF; para. [0019, 0097, 0108, 0113, 0122, 0129]; tables 6-7);
transferrin (insulin-transferrin-selenium complex; para. [0019-0020, 0097, 0108, 0112, 0121, 0129]; Tables 3,5 and 7; claims 8-9);
a TGFβ type I receptor inhibitor selected from the group consisting of A83-01, SB431542, Repsox, SB505124, SB525334, SD208, LY36494, and SJN2511 (para. [0019]).
Hoffman
Hoffman et al. (WO-2003020722-A1; citations refer to attached translation; henceforth “Hoffman”) teaches dihydropteridinones of formula (I)
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wherein R1 is a radical selected from the group consisting of hydrogen, NH, XH, halogen and a C 1 -C 3 -alkyl group which is optionally substituted by one or more halogen atoms,
R is a radical selected from the group consisting of hydrogen, CHO, XH, -X-C 1 -C 2 -alkyl and an optionally substituted CrC 3 -alkyl group,
R3 , R4 are identical or different , a radical selected from the group consisting of optionally substituted C 1 -C 8 -alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, aryl, Heteroaryl, C 3 -C 8 cycloalkyl, C 3 -C 8 heterocycloalkyl, -X-aryl, -X-heteroaryl, -X-cycloalkyl, -X-heterocycloalkyl, -NR 8 -aryl, -NR 8 -heteroaryl, -NR 8 -cycloalkyl, and -NR 8 heterocycloalkyl, or a radical selected from the group consisting of hydrogen, halogen, COXR 8 , CON (R 8 ) 2) COR 8 and XR 8 ,
or R 3 and R 4 together form a 2- to 5-membered alkyl bridge which can contain 1 to 2 heteroatoms,
R5 is hydrogen or a radical selected from the group consisting of optionally substituted Cι-Cι 0 alkyl, C 2 -Cι 0 alkenyl, C 2 -C 10 alkynyl, aryl, heteroaryl and -C 3 -C 6 cycloalkyl,
or R3 and R5 or R4 and R5 together form a saturated or unsaturated C 3 -C 4 alkyl, which may contain 1 to 2 heteroatoms,
R6 optionally substituted aryl or heteroaryl,
R7 is hydrogen or -CO-XC 1 -C 4 alkyl, and X each independently of one another, O or S,
R8 selected each independently, hydrogen or a radical from the group consisting of optionally substituted Cι-C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 -alkynyl and phenyl, if appropriate in the form of their tautomers, their racemates, their enantiomers, their diastereomers and their mixtures, and if appropriate their pharmacologically acceptable acid addition salts (claim 1 and Description; see in particular Table 1).
Embodiments of the structure of Hoffman are encompassed by the structure of Formula (I) of instant claims (see claim 1 and table 1).
Hoffman teaches a composition comprising a cell culture media (F12 medium) and the dihydropteridinones (“active substances were added to the cells”) for cancer cells (cervical carcinoma tumor cell line HeLaS3) (pg. 109 7th para.).
Conclusion
No claim is allowable.
Correspondence
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/BRIANA N EBBINGHAUS/Examiner, Art Unit 1632
/EMILY A CORDAS/Primary Examiner, Art Unit 1632
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