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 1-16 are pending.
Claims 12-13 are withdrawn.
Claims 1-11 and 14-16 are under examination.
Election/Restrictions
Applicant’s election with traverse of the following invention
Invention
Group I, claims 1-11 and 14-16, drawn to a primary cell culture medium for culturing primary lung cancer epithelial cells.
in the reply filed on 22nd, July, 2026 is acknowledged.
Applicant traverses on the grounds stated below which are not persuasive for the reasons stated below.
Applicant traverse on the grounds that “Group I claims are directed to a primary cell culture medium for culturing primary lung cancer epithelial cells, Group II and Group III claims are directed to
methods using compounds according to claim 1. Thus, as Groups I-III include the same primary cell culture medium, they are clearly related to each other as aspects of a single inventive concept. Significantly, a search for a primary cell culture medium as delineated in claim 1 would inevitably function to find art pertaining to methods for their use. As provided, the search burden is substantially minimized by the existing overlap of the claims of Groups I-III” (pg. 14). “Applicant respectfully submits that the PCT Rules, which are the governing provisions in the instant case, specifically permit product claims and process of use claims to be examined together in one application, as acknowledged by the Examiner on page 4 of the Office Action (pg. 14).
In response, this is not found persuasive for several reasons. First, instant claims are drawn to a product and two methods, which are not one of the allowed combinations of inventions. The PCT rules provide for the examination of the first claimed product, the first claimed method of making that product, and the first claimed method of using that product in one application, but do not provide for the examination of multiple products or unrelated methods (see 37 CFR § 1.475(a)-(d)).
Next, the Lack of Unity previously set forth does not allege that there is no shared inventive concept, but rather alleges that the technical feature fails to make a contribution over the prior art as set forth previously.
Lastly, while Applicant references searches, undue search burden are not a criteria for election/restriction purposes under 35 USC §121 and 35 USC § 372 and therefore this is not found persuasive.
Applicant additionally traverses on the grounds that the Liu reference is disqualified under 35 U.S.C. §102(b)(2)(C) (pg. 14).
In response, this is not found persuasive because while U.S.C. §102(b)(2)(C) applies to overcoming prior art for rejections which use art under U.S.C. §102 or U.S.C. §103, this exception does not apply to art that is used to show a lack of Unity of Invention.
It is additionally noted that Applicant’s statement concerning common ownership also does not meet the requirements to disqualify the Liu reference. Specifically, Applicant is directed to MPEP 717.02 (a) which states that In order to invoke common ownership to except a disclosure as prior art, the applicant (or the patent owner) must provide a statement that the disclosure of the subject matter on which the rejection is based and the claimed invention were owned by the same person or subject to an obligation of assignment to the same person not later than the effective filing date of the claimed invention. The statement should either be on or begin on a separate sheet and must not be directed to other matters (37 CFR 1.4(c) ). The statement must be signed in accordance with 37 CFR 1.33(b). In the instant case, the statement is made together with response to the restriction requirement and is therefore directed to other matters. There is an additional document provided with the response on a separate sheet with information on the patent assignment of the Liu reference. This is also insufficient because this document does not include the required statement that the disclosure of the subject matter on which the rejection is based and the claimed invention were owned by the same person or subject to an obligation of assignment to the same person not later than the effective filing date of the claimed invention, and is also not signed in accordance with 37 CFR 1.33(b).
Finally, it is additionally noted that the technical feature is also obvious over a different combination of references of Liu et al. (US-20230212523-A1; published 6th, July, 2023 with priority to 26th, May, 2020; henceforth “Liu1”) in view of Fisher et al. (Semin Immunol. 2014 Feb;26(1):38-47. Epub 2014 Mar 3.; henceforth “Fisher”) as set forth below and therefore does not make a contribution over the prior art.
The requirement is still deemed proper and is therefore made FINAL.
Claims 12-13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Priority
The instant application was filed on 8th, January, 2024 and is a 371 of PCT/CN2021/108807 filed on 28th, July, 2021 and claims priority to CHINA 202110773847.3 filed on 8th, July, 2021.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows: The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of the first paragraph of 35 U.S.C. 112. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Thus the instant claims are being given the filing date of PCT/CN2021/108807 filed on 28th, July, 2021.
Objections to Abstract
Informalities
The abstract of the disclosure is objected to because lines 1 and 10 each recite “primay” which appears to be a typographical error for “primary.”
A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Objections to Abstract
Trade Name or Marks used in Commerce
The abstract is objected to because it uses the term “B27” (line 3) 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, RPMI, Matrigel, 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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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 Interpretation
Claim 10 recites the transitional phrase “characterized in.” Applicant is directed to MPEP 2111.03 (I) for information on transitional phrases. The transitional phrases "comprising", "consisting essentially of" and "consisting of" define the scope of a claim with respect to what unrecited additional components or steps, if any, are excluded from the scope of the claim and the determination of what is or is not excluded by a transitional phrase must be made on a case-by-case basis in light of the facts of each case see MPEP 2111.03. Other transitional phrases must be interpreted in light of the specification to determine whether open or closed claim language is intended (see MPEP 2111.03 (V)).
MPEP 2111.03 (I) states the "comprising", which is synonymous with "including," "containing," or "characterized by," is inclusive or open-ended and does not exclude additional, unrecited elements or method steps (see MPEP 2111.03 (I)).
In the instant case, the specification is absent to specific guidance on the breadth of the transitional phrase “characterized in” and therefore, because this phrase most closely resembles the transitional phrase "characterized by," the phrase is interpreted as inclusive or open-ended and does not exclude additional, unrecited elements or method steps.
Claim Objections
Claim 10 is objected to because of the following informalities.
Claim 10 recites “characterized in that, being” 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 appear to be open-ended (see MPEP 2111.03 (I)). However, it is grammatically improper and also unnecessarily redundant to include two transitional phrases and it is recommended that Applicant amend to one transitional phrase 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 1-11 and 14-16 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,” “RPMI-1640” (which contains the trademarked term RPMI) 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, RPMI 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, DMEM, and RPMI 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), B27 (number 77129891) and RPMI (number 78115891) are dead/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 2-16 are also rejected because they do no clarify the issue.
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 Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The 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.
Claims 1-11 and 14-16 are rejected under 35 U.S.C. 103 as being obvious over Liu et al. (US-20230212523-A1; published 6th, July, 2023 with priority to 26th, May, 2020; henceforth “Liu1”) in view of Fisher et al. (Semin Immunol. 2014 Feb;26(1):38-47. Epub 2014 Mar 3.; henceforth “Fisher”).
The applied reference of Liu1 has a common Inventors and Assignee with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Regarding claim 1, Liu1 discloses a primary cell culture medium comprising an MST1/2 kinase inhibitor (“a primary cell culture medium that contains an MST1/2 kinase inhibitor; abstract; para. [0008, 0013, 0017, 0018-0019, 0022, 0070-0072]; see in particular claims 1-5 and 7)
at least one ROCK inhibitor selected from the group consisting of Y27632, fasudil, and H-1152 (claim 7; para. [0020-0021, 0094, 0100, 0115, 0119]; Tables 3-5;
fibroblast growth factor 7 (para. [0020, 0100]; Table 3; Figure 1A; claim 7);
at least one additive selected from the group consisting of B27 additive and N2 additive (para. [0094, 0098, 0125]; Table 3-4);
hepatocyte growth factor (para. [0020-0021, 0094, 0100, 0106, 0114, 0119; Tables 3-4; Fgure 1A; claim 7);
insulin-like growth factor 1 (Figure 1A; para. [0020-0021, 0094, 0100, 0105, 0113, 0119]; Tables 3-4; claim 7);
at least one TGFβ type I receptor inhibitor selected from the group consisting of A83-01, SB431542, Repsox, SB505124, SB525334, SD208, LY36494, and SJN2511 (para. [0020-0021, 0094, 0100, 0109, 0117, 0119]; claim 7; Tables 3-4)
wherein, the MST1/2 kinase inhibitor comprises a compound of Formula (I) or a pharmaceutically acceptable salt, or a solvate thereof (Liu1 discloses an identical Markush to Formula (I) in para. [0008] and claim 1)
wherein,
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Formula (I)
R1 is selected from C1-C6 alkyl, C3-C6 cycloalkyl, C4-C8 cycloalkylalkyl, C2-C6 spirocycloalkyl, and aryl optionally substituted with 1-2 independent R6, aryl C1-C6 alkyl optionally substituted with 1-2 independent R6 and heteroaryl optionally substituted with 1-2 independent R6;
R2 and R3 are each independently selected from C1-C6 alkyl;
R4 and R5 are each independently selected from hydrogen, C1-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, and C3-C6 heterocyclyl C1-C6 alkyl;
R6 is selected from halogen, Cl-C6 alkyl, Cl-C6 alkoxy, and C1-C6 haloalkyl (see claims 1-5).
However, regarding claim 1, although Liu1 teaches the culture medium is for proliferation (“so that the primary cells proliferate rapidly”; abstract) of cancer cells (laryngeal cancer epithelial cells; claim 1), Liu1 is silent to including interleukin-6 in the medium.
Nevertheless, regarding claim 1, Fisher teaches IL-6 acts intrinsically on tumor cells through numerous downstream mediators to support cancer cell proliferation, survival, and metastatic dissemination (abstract) and Fisher teaches Initiation of IL-6 signaling pathways in cancer cells activates mediators of cellular proliferation (pg. 39 col. 2).
Therefore, regarding claim 1, it would have been obvious to a person or ordinary skill in the art before the effective filing date of the claimed invention to prepare the cell culture medium of Liu1, and combine the known prior art element of the IL-6 of Fisher to obtain the predictable result of a cell culture medium. One of ordinary skill would have been motivated to do so as taught by Fisher to support proliferation and survival of the cancer cells of Liu1. Regarding the reasonable expectation of success, Liu1 evidences preparation of cell culture medias for cancer cells (abstract; Figure 1A; para. [0020-0021, 0094, 0100, 0105, 0113, 0119]; Tables 3-4; claim 7).
Regarding the preamble of claim 1, the preamble merely states, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction (see MPEP 2111.02) See also Rowe v. Dror, 112 F.3d 473, 478, 42 USPQ2d 1550, 1553 (Fed. Cir. 1997) ("where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation"). In the instant case, Liu1 in view of Fisher suggest all the required structural elements of the complete invention in the claim body and therefore the meets instant claims. Furthermore, because Liu in view of Fisher teach a cell culture medium comprising the claimed components, it is capable of meeting the recited intended use of “for culturing primary lung cancer epithelial cells.”
Regarding claim 2, further to the discussion of claim 1 above, Liu1 teaches
R1 is selected from C1-C6 alkyl, C3-C6 cycloalkyl, C4-C8 cycloalkylalkyl, C2-C6 spirocycloalkyl, and phenyl optionally substituted with 1-2 independent R6, naphthyl optionally substituted with 1-2 independent R6, phenylmethyl optionally substituted with 1-2 independent R6 and thienyl optionally substituted with 1-2 independent R6; R2 and R3 are each independently selected from C1-C3 alkyl;
R4 and R5 are each independently selected from hydrogen, Cl-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 C1-C6 alkyl, and tetrahydropyranyl C1-C6 alkyl;
R6 is selected from halogen, C1-C6 alkyl, C1-C6 alkoxy, and C1-C6 haloalkyl (para. [0009-0016]; claim 2).
Regarding claim 3, further to the discussion of claim 1 above, Liu1 teaches wherein 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 substituted with 1-2 independent R6,
thienyl optionally substituted with 1-2 independent R6, and phenylmethyl optionally substituted
with 1-2 independent R6;
R5 is selected from hydrogen, C1-C6 alkyl, and C3-C6 cycloalkyl;
R6 is independently selected from halogen, C1-C6 alkyl, and C1-C6 haloalkyl (para. [0013]; claim 3).
Regarding claim 4, further to the discussion of claim 1 above, Liu1 teaches
R1 is phenyl optionally substituted with 1-2 independent R6;
R5 is hydrogen;
R6 is fluoro, methyl or trifluoromethyl (para. [0009-0016; claim 4).
Regarding claim 5, further to the discussion of claim 1 above, Liu1 teaches the compounds labeled from 1 to 52 as the MST1/2 kinase inhibitor (pg. 2-10; claim 5).
Regarding claim 6, further to the discussion of claim 1 above, Liu1 teaches the amount of the MST1/2 kinase inhibitor in the culture medium is 2.5-10 μM (para. [0019]; claim 13).
Regarding claim 7, further to the discussion of claim 1 above, Liu1 teaches
the amount of fibroblast growth factor 7 is 20-80 ng/ml which lies within the claimed 5-160 ng/ml and thereby makes it obvious;
the amount of hepatocyte growth factor is 10-40 ng/ml which lies within the claimed 5-160 ng/ml and thereby makes it obvious;
the amount of insulin-like growth factor 1 is 10-40 ng/ml which lies within the claimed 5-160 ng/ml and thereby makes it obvious;
the amount of the TGFβ type I receptor inhibitor is 125-500 nM which lies within the claimed 62.5-500 nM and thereby makes it obvious (para. [0021]).
Regarding claim 7, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). It is routine procedure to optimize component amounts to arrive at an optimal product that is superior for its intended use, since it has been held where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. See M.P.E.P. §2144.05.
Additionally, regarding claim 7, applicant is reminded that generally, differences in concentration will not support patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical (MPEP 2144.05 II).
Regarding claim 8, further to the discussion of claim 1 above, Liu1 teaches
the MST1/2 kinase inhibitor is Compound 1 (pg. 2; claim 5);
the ROCK inhibitor is Y27632 (para. [0021]);
the TGF type I receptor inhibitor is A83-01 (para. [0021]).
Regarding claim 9, further to the discussion of claim 1 above, Liu1 teaches an initial medium selected from the group consisting of DMEM/F12, DMEM, F12 (para. [0029, 0086, 0090-0091, 0101, 0134, 0162]; Tables 1, 3, 5) and , Liu1 teaches Primocin (para. [0029, 0086, 0091 Tables 1, 3-4).
Regarding claim 10, further to the discussion of claim 1 above, Liu1 teaches the medium is free of serum, bovine pituitary extract, Wnt agonists, R-spondin family proteins, BMP inhibitors, nicotinamide, or N-acetylcysteine (claim 9).
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 as suggested by Liu1 in view of Fisher 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 claim 14, further to the discussion of claim 1 above, Liu1 teaches the amount of the MST1/2 kinase inhibitor in the culture medium is 2.5-10 μM (para. [0019]; claim 13) which overlaps with the claimed range of 5-7.5 μM and thereby makes it obvious (see In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) and M.P.E.P. §2144.05 cited above).
Regarding claim 15, further to the discussion of claim 1 above, Liu1 teaches the amount of fibroblast growth factor 7 is 20-80 ng/ml which lies within the claimed 10-80 ng/ml and thereby makes it obvious (para. [0021]) (see In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) and M.P.E.P. §2144.05 cited above).
Regarding claim 16, further to the discussion of claim 1 above, Liu1 teaches the amount of fibroblast growth factor 7 is 20-80 ng/ml which overlaps with the claimed 20-40 ng/ml and thereby makes it obvious (para. [0021]) (see In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) and M.P.E.P. §2144.05 cited above).
Hence, the claimed invention as a whole was prima facie obvious.
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
U.S. Co-pending Application No. 17927530
Claims 1-8, 10-12 and 14-16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 and 13-14 of U.S. co-pending application No. 17927530 (claim set filed 3rd, February, 2026) in view of Gu et al. (Journal of Biotech Research, Volume 3, 2011, pages 7-18; henceforth “Gu”) and Fisher et al. (Semin Immunol. 2014 Feb;26(1):38-47. Epub 2014 Mar 3.; henceforth “Fisher”).
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 makes obvious the primary cell culture medium of the 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 ‘530 claims a primary cell culture medium for culturing laryngeal cancer epithelial cells comprising an MST1/2 kinase inhibitor of Formula (I) or a pharmaceutically acceptable salt, or a solvate thereof; at least one ROCK inhibitor selected from the group consisting of Y27632, fasudil, and H-1152; fibroblast growth factor 7; hepatocyte growth factor; insulin-like growth factor 1; at least one TGFβ type I receptor inhibitor selected from the group consisting of A83-01, SB431542, Repsox, SB505124, SB525334, SD208, L Y36494, and SJN2511 (claim 1).
However, regarding claim 1, although U.S. Co-pending App ‘530 claims the medium is for cancer cells (laryngeal cancer epithelial cells), U.S. Co-pending App ‘530 does not claim the primary cell culture medium comprises B27 additive.
Nevertheless, regarding claim 1, Gu teaches culturing primary cancer cells in a culture medium that includes B27 (“Our study identifies B27 as an essential component of culture medium necessary for sustained propagation and enrichment” abstract; pg. 9 col. 2; Figure 3; pg. 12). Gu teaches B27 supplement is crucial for serially maintaining tumorspheres in vitro (pg. 12 col. 1). Gu teaches B27 plays an important role in maintaining and promoting tumorsphere propagation in vitro (pg. 12 col. 2; pg. 13 col. 1; pg. 14 col. 1 ; Figure 4).
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 medium as claimed by U.S. Co-pending App ‘530, and combine the known prior art element of the B27 supplement of Gu to obtain the predictable result of a cell culture medium. One of ordinary skill would have been motivated to do so as taught by Gu to maintain and promote tumorsphere propagation in vitro (pg. 12 col. 1) and to allow for sustained propagation and enrichment (abstract; pg. 9 col. 2; Figure 3; pg. 12). Regarding the reasonable expectation of success, Gu evidences preparation of cell culture media comprising B27 (pg. 9 col. 2).
However, regarding claim 1, U.S. Co-pending App ‘530 does not claim the primary cell culture medium comprises interleukin 6.
Nevertheless, regarding claim 1, Fisher teaches IL-6 acts intrinsically on tumor cells through numerous downstream mediators to support cancer cell proliferation, survival, and metastatic dissemination (abstract) and Fisher teaches Initiation of IL-6 signaling pathways in cancer cells activates mediators of cellular proliferation (pg. 39 col. 2).
Therefore, regarding claim 1, it would have been obvious to a person or ordinary skill in the art before the effective filing date of the claimed invention to prepare the cell culture as claimed by U.S. Co-pending App ‘530 in view of Gu, and combine the known prior art element of the IL-6 of Fisher to obtain the predictable result of a cell culture medium. One of ordinary skill would have been motivated to do so as taught by Fisher to support proliferation and survival of the cancer cells of U.S. Co-pending App ‘530. Regarding the reasonable expectation of success, Gu evidences preparation of cell culture medias for cancer cells (pg. 9 col. 2).
Regarding the preamble of claim 1, the preamble merely states, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction (see MPEP 2111.02) See also Rowe v. Dror, 112 F.3d 473, 478, 42 USPQ2d 1550, 1553 (Fed. Cir. 1997) ("where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation"). In the instant case U.S. Co-pending App ‘530 in view of Gu and Fisher suggest all the required structural elements of the complete invention in the claim body and therefore the meets instant claims. Furthermore, because U.S. Co-pending App ‘530 in view of Gu and Fisher teach a cell culture medium comprising the claimed components, it is capable of meeting the recited intended use of “for culturing primary lung cancer epithelial cells.”
Regarding claim 2, further to the discussion of claim 1 above, U.S. Co-pending App ‘530 claims
R1 is selected from C1-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 ‘530 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 ‘530 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 ‘530 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 ‘530 claims the amount of the MST1/2 kinase inhibitor is 2.5 µM-10 µM (claim 13).
Regarding claim 7, further to the discussion of claim 1 above, U.S. Co-pending App ‘530 claims the amount of the ROCK inhibitor is 1.5-20 µM (claim 8), which overlaps with the claimed range of 2.5-15 μM and thereby makes It obvious ((see In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) and M.P.E.P. §2144.05 cited above).
Regarding claim 8, further to the discussion of claim 1 above, U.S. Co-pending App ‘530 claims
the MST1/2 kinase inhibitor is Compound 1 (claim 5).
Regarding claim 10, further to the discussion of claim 1 above, U.S. Co-pending App ‘530 claims the medium is free of serum, bovine pituitary extract, Wnt agonists, R-spondin family proteins, BMP inhibitors, nicotinamide, or N-acetylcysteine (claim 9).
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 as claimed by U.S. Co-pending App ‘530 in view of Gu and Fisher 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 claim 14, further to the discussion of claim 1 above, U.S. Co-pending App ‘530 claims the amount of the MST1/2 kinase inhibitor in the culture medium is 2.5-10 μM (claim 13) which overlaps with the claimed range of 5-7.5 μM and thereby makes it obvious (see In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) and . See M.P.E.P. §2144.05 cited above).
Regarding claim 15, further to the discussion of claim 1 above, U.S. Co-pending App ‘530 claims the amount of fibroblast growth factor 7 is 5-80 ng/ml which overlaps with the claimed 10-80 ng/ml and thereby makes it obvious (claim 8) (see In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) and . See M.P.E.P. §2144.05 cited above).
Regarding claim 16, further to the discussion of claim 1 above, U.S. Co-pending App ‘530 claims the amount of fibroblast growth factor 7 is 5-80 ng/ml which overlaps with the claimed 10-40 ng/ml and thereby makes it obvious (claim 8) (see In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) and M.P.E.P. §2144.05 cited above).
Since instant application claims are obvious over cited Application claims, in view of Gu and Fisher, said claims are not patentably distinct.
Claims 9 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 and 13-14 of copending application No. 17927530 (claim set filed 3rd, February, 2026) in view of Gu et al. (Journal of Biotech Research, Volume 3, 2011, pages 7-18; henceforth “Gu”) and Fisher et al. (Semin Immunol. 2014 Feb;26(1):38-47. Epub 2014 Mar 3.; henceforth “Fisher”) as applied to claim 1 above, and in further view of ThermoFisher (2015, accessed at: https://web.archive.org/web/20151015055302/http://www.thermofisher.com/order/catalog/product/15140122).
The teachings of U.S. Co-pending App ‘530, Gu, and Fisher above are incorporated herein in their entirety.
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 makes obvious the primary cell culture medium of the instant application.
Although the claims at issue are not identical, they are not patentably distinct for the reasons stated below.
Regarding claim 9, further to the discussion of claim 1 above, U.S. Co-pending App ‘530 does not claim the medium includes streptomycin/penicillin.
Nevertheless, regarding claim 9, ThermoFisher teaches including streptomycin/penicillin in cell culture mediums to prevent bacterial contamination of cell cultures due to their effective combined action against gram-positive and gram-negative bacteria (Description 1st para.).
Therefore, regarding claim 9, 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 medium as claimed by U.S. Co-pending App ‘530 in view of Gu and Fisher, and combine the known prior art element of the streptomycin/penicillin of ThermoFisher to obtain the predictable result of a cell culture medium. One of ordinary skill would have been motivated to do so as taught by ThermoFisher to prevent bacterial contamination of cell cultures (Description 1st para.).
Since instant application claims are obvious over cited Application claims, in view of Gu, Fisher, and ThermoFisher, 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, 18690412, 18692569, and 18700796 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) or a pharmaceutically acceptable salt, or a solvate thereof; at least one ROCK inhibitor selected from the group consisting of Y27632, fasudil, and H-1152; at least one additive selected from the group consisting of B27 additive and N2 additive; hepatocyte growth factor; 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 (claim 1).
U. S. Co-pending App ‘971 does not claim the required elements of instant Application claims of fibroblast growth factor 7; insulin-like growth factor 1; and interleukin 6 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) or a pharmaceutically acceptable salt, or a solvate thereof; at least one ROCK inhibitor of Y27632; at least one additive selected from the group consisting of B27 additive and N2 additive and hepatocyte growth factor (claim 1).
U. S. Co-pending App ‘412 does not claim the required elements of instant Application claims of fibroblast growth factor 7; insulin-like growth factor 1; interleukin 6; 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 and these are not fairly taught or suggested by the prior art.
U.S. Co-pending Application No. 18/692,569
U. S. Co-pending App ‘569 (claim set filed 15th, March, 2024), claims a cell culture media comprising an MST1/2 kinase inhibitor of Formula (I) or a pharmaceutically acceptable salt, or a solvate thereof; at least one ROCK inhibitor selected from the group consisting of Y27632, fasudil, and H-1152; a fibroblast growth factor; at least one additive selected from the group consisting of B27 additive and N2 additive; 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 ‘412 does not claim the required elements of instant Application claims of fibroblast growth factor 7; hepatocyte growth factor; insulin-like growth factor 1 and interleukin 6 and these are not fairly taught or suggested by the prior art.
U.S. Co-pending Application No. 18700796
U. S. Co-pending App ‘796 (claim set filed 12th, April, 2024) claims a cell culture media comprising an MST1/2 kinase inhibitor of Formula (I) or a pharmaceutically acceptable salt, or a solvate thereof; at least one ROCK inhibitor selected from the group consisting of Y27632, fasudil, and H-1152;
B27 additive and N2 additive; and insulin-like growth factor 1.
U. S. Co-pending App ‘412 does not claim the required elements of instant Application claims of fibroblast growth factor 7; hepatocyte growth factor; interleukin 6; 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 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.).
Triastuti does not teach an MST1 kinase inhibitor of Formula (I); at least one ROCK inhibitor selected from the group consisting of Y27632, fasudil, and H-1152; fibroblast growth factor 7; at least one additive selected from the group consisting of B27 additive and N2 additive; hepatocyte growth factor; insulin-like growth factor 1; interleukin 6; or at least one TGFβ type I receptor inhibitor selected from the group consisting of A83-01, SB431542, Repsox, SB505124, SB525334, SD208, LY36494, and SJN2511.
Liu2
Liu et al. (WO-2020073906-A1; henceforth “Liu2”) 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).
Liu2 discloses the composition comprises Ringer’s injection or lactated Ringer’s injection.
Liu2 does not teach at least one ROCK inhibitor selected from the group consisting of Y27632, fasudil, and H-1152; fibroblast growth factor 7; at least one additive selected from the group consisting of B27 additive and N2 additive; hepatocyte growth factor; insulin-like growth factor 1; interleukin 6; or at least one TGFβ type I receptor inhibitor selected from the group consisting of A83-01, SB431542, Repsox, SB505124, SB525334, SD208, LY36494, and SJN2511.
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 -C10 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 C1-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.).
Hoffman does not teach at least one ROCK inhibitor selected from the group consisting of Y27632, fasudil, and H-1152; fibroblast growth factor 7; at least one additive selected from the group consisting of B27 additive and N2 additive; hepatocyte growth factor; insulin-like growth factor 1; interleukin 6; or at least one TGFβ type I receptor inhibitor selected from the group consisting of A83-01, SB431542, Repsox, SB505124, SB525334, SD208, LY36494, and SJN2511.
Conclusion
No claim is allowable.
Correspondence
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/BRIANA N EBBINGHAUS/Examiner, Art Unit 1632
/PETER PARAS JR/Supervisory Patent Examiner, Art Unit 1632
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