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
As of the Non-Final Office Action mailed 3/26/2025, claims 30-46 were pending and claims 35-36, 39-43, and 45-46 were withdrawn from consideration for being drawn to non-elected invention(s).
In Applicant's Response filed on 9/23/2025, claims 30-31, 37-38, and 44 were amended, claims 32-34 were canceled, and claims 47-50 were newly added.
As such, claims 30-31 and 35-50 are pending and claims 30-31, 37-38, and 47-50 have been examined herein.
Withdrawn Objections/Rejections
The objection of record to the specification for minor informalities has been withdrawn.
The objection of record to claims 31, 37, and 38 for minor informalities has been withdrawn in view of Applicant’s amendments to the claims.
The rejection of record of claims 37-38 and 44 under 35 USC § 112(b) have been withdrawn in view of Applicant’s amendment to the claims.
The rejection of record of claims 30-32 under 35 USC § 102(a)(1) and (a)(2) as being anticipated by Liu et al (WO 2016079146 A1, 17 Nov 2014; published 26 May 2016) has been withdrawn in view of Applicant’s amendments to claim 30. The rejection of claim 32 is moot in view of its cancelation.
The rejection of record of claims 33-34, 38, and 44 under 35 USC § 103 as being unpatentable over Liu et al as applied to claims 30-32 and further in view of Chen et al (US 9279103 B2, 5 Aug 2011), Nicholas et al (US 10100279 B2, 14 Mar 2014), and Haigh (Research Gate, 2016) have been withdrawn in view of Applicant’s amendments to claim 30. The rejection of claim 33-34 is moot in view of their cancelation.
The rejection of record of claim 37 under 35 USC § 103 as being unpatentable over Liu et al as applied to claims 30-32 have been withdrawn in view of Applicant’s amendments to claim 30.
The rejection of record of claim 30-32 on the ground of double patenting over claims 1-2 and 4-5 of US patent 10,745,670 B2 in view of Liu et al has been withdrawn in view of Applicant’s amendments to claim 30. The rejection of claim 32 is moot in view of its cancelation.
The rejection of record of claim 30-32 on the ground of double patenting over claims 1-6 of US patent 11,913,018 B2 in view of Liu et al has been withdrawn in view of Applicant’s amendments to claim 30. The rejection of claim 32 is moot in view of its cancelation.
New Grounds of Objections/Rejections Necessitated by Amendments
Claim Objections
Claims 30 and 47 objected to because of the following informalities:
Claim 30 numerous medium components which are incorrectly capitalized.
Claim 47 recites numerous medium components which are incorrectly capitalized.
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 30-31, 37-38, and 47-50 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 30 recites “a porcine expanded potential stem cell culture medium.” It is unclear what Applicant is intending to claim when stating “porcine expanded potential.” The specification does not provide adequate description or definition such that the phrase could be reasonably understood. Thus, the claim is indefinite. For the purpose of compact prosecution, the examiner is interpreting that the claim recites an intended use for the medium to culture porcine stem cells (see MPEP 2111.02). Claims 31 and 37-38 are included in this rejection for being dependent on indefinite claim 30.
Claim 30, 44, and 47 contains the trademark/trade name neurobasal. 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 media for neuronal cells and, accordingly, the identification/description is indefinite. Claims 31 and 37-38 are included in this rejection for being dependent on indefinite claim 30. Claims 44, 48-50 are included in this rejection for being dependent on indefinite claim 47.
Claim 47 recites “a human expanded potential stem cell culture medium.” It is unclear what Applicant is intending to claim when stating “human expanded potential.” The specification does not provide adequate description or definition such that the phrase could be reasonably understood. Thus, the claim is indefinite. For the purpose of compact prosecution, the examiner is interpreting that the claim recites an intended use for the medium to culture human stem cells (see MPEP 2111.02). Claims 44, 48-50 are included in this rejection for being dependent on indefinite claim 47.
It is noted that any interpretation of the claims set forth above does not relieve Applicant of the responsibility of responding to rejections made based on said interpretations. If the actual interpretation of the claims is different than that posited by the Examiner, additional rejections and art may be readily applied in a subsequent final Office action.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 30-31, 37-38, 44, and 47-50 is/are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al (WO 2016079146 A1, 17 Nov 2014; published 26 May 2016; previously cited) in view of Chen et al (US 9,279,103 B2, 5 Aug 2011; Published 8 March 2016; previously cited), Nicholas et al (US 10,100,279 B2, 14 March 2014; Published 16 Oct 2016; previously cited) and Haigh (Research Gate, 2016; Retrieved from the Internet 20 March 2025; previously cited).
Liu teaches production of a population of expanded potential stem cells, requiring culturing the cells in a medium containing one or more of a SRC inhibitor (see claim 1 of Liu). The medium can also contain a basal medium of DMEM/F12, chemically defined lipids, N2, B27; Glutamine-Penicillin- Streptomycin; Non-Essential Amino Acids (i.e., NEAA); vitamin C, LIF and IGF-II (p. 17 line 17; p. 32 lines 21-26). Suitable SRC inhibitors include A-419259, WH-4-023 and Tankyrase inhibitor XAV939 (p. 24 line 1). It can also include 2-mercaptoethanol (i.e., beta-mercaptoethanol), CHIR99021, and IWR-1 (p. 17 line 10; p. 23, line 36; p. 29 line 10-11). The cells are human or porcine (see claim 25 of Liu). The reference further teaches that the medium can contain activin and/or FBS for optimal cell proliferation (p. 29 lines 31-32) (“wherein the medium further comprises: (i) Lif protein; and (ii) Activin or FBS” as in instant claim 31 and claim 48). It also teaches that the medium can contain an SRK inhibitor such as PP1, PP2, and CGP77675 (p. 25 lines 30-31) as well as serum albumin (i.e., bovine serum albumin which is bovine fraction V) (p. 17, line 18). This reads on “A porcine expanded potential stem cell culture medium comprising: a basal medium, an SRC inhibitor, a vitamin C supplement, and a Tankyrase inhibitor wherein the basal medium is DMEM/F-12 or DMEM, wherein the SRC inhibitor is WH-4-023 or A-419259, wherein the Tankyrase inhibitor is endo-IWR-1 or XAV939, wherein the culture medium further comprises N2 supplement, B27 supplement, Glutamine Penicillin-Streptomycin, NEAA, 2-mercaptoethanol, or CHIR99021 or a combination thereof, and wherein the culture medium further comprises . . . bovine albumin fraction V” as in instant claim 30 in-part and “A human expanded potential stem cell culture medium comprising: a basal medium, an SRC inhibitor, a vitamin C supplement, and a Tankyrase inhibitor wherein the basal medium is DMEM/F-12 or DMEM, wherein the SRC inhibitor is WH-4-023 or A-419259, wherein the Tankyrase inhibitor is endo-IWR-1 or XAV939, wherein the culture medium further comprises N2 supplement, B27 supplement, Glutamine Penicillin-Streptomycin, NEAA, 2-mercaptoethanol, or CHIR99021 or a combination thereof, and wherein the culture medium further comprises . . . bovine albumin fraction V” as in instant claim 47 in-part. Liu teaches that the medium can contain DMEM/F12, 100 uM beta-mercaptoethanol (p. 17 line 10), 50 ug/mL vitamin C (p. 71 line 30), NEAA, N2, B27, 5 uM XAV939 (p. 71, line 31), 0.5 to 10 ng/mL LIF (p. 61 line 15-17), activin 1-100 ng/mL and 0.5% FBS (p. 72, line 1), penicillin-streptomycin-glutamine, defined lipids, A419259, CHIR99021, and IWR-1 (also see above 102 rejection). The medium can also contain serum albumin (such as i.e., bovine serum albumin which is bovine fraction V) (p. 17, line 18). The reference further teaches that A419259 is a potent pyridopyrimidine inhibitor of SFKs, XAV939 stabilizes Axon, CHIR99021 promotes metabolic and biosynthetic processes in cells, and LIF enhances ES cells self-renewal and promotes rare totipotent cells (p. 37, lines 24-33) (“F12 DMEM . . . Penicillin-Streptomycin-Glutamine . . . NEAA . . . 110 uM 2-Mercaptoethanol . . . N2 . . . B27, . . . 64 ug/ml Vitamin C . . . Bovine Fraction V . . . defined lipids, . . . 2.5 uM XAV939, endo-IWR-1, . . . A419259, CHIR99021, and 10 ng/ml Lif protein.” as in instant claim 44 in-part). Liu also teaches that the medium can contain LIF in concentrations of 0.5 to 10 ng/mL (p. 61 line 15-17), activin in amounts of 1-100 ng/mL, and 0.5% FBS (p. 72, line 1). It also teaches that LIF enhances ES cells self-renewal and promotes rare totipotent cells and that activin and FBS optimize cell proliferation (p. 37, lines 24-33) (“wherein: (i) the LIF protein is in the range from 1 to 20 ng/ml; (ii) the Activin is in the range from 10 to 50 ng/ml; (iii) the FBS is in the range from 0.1 to 0.5%” as in instant claim 37 and 49 in-part). Please note that while Liu does not teach concentration of, e.g., DMEM/F12, A419259, CHIR99021, etc., “generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)” (see MPEP 2144.05(II)(A)).
The difference between the instant invention and Liu is that it does not teach that the culture medium further comprises (i) ITS-X, trace element B, trace element C, reduced glutathione, and (ii) neurobasal medium, sodium pyruvate, or a combination thereof.
Chen teaches a fully defined media that supports cell viability, proliferation, cloning, and derivation (abstract). The medium contains water, salts, amino acids, vitamins, glucose, insulin, an FGF, selenium, transferrin (see claim 1 of Chen; ITS is insulin-transferrin-selenium) (“ITS-X” as in instant claims 30 in-part, 34 in-part, 38, 44 in-part, and 50). The medium also contains trace elements B and C (see example 3 of Chen) (“trace elements B and trace elements C” as in instant claim 30 in-part, 47 in-part, and 44 in-part). Please note that while Chen does not teach concentration of ITS or trace elements B and C present in the medium, “generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)” (see MPEP 2144.05(II)(A)).
Nicholas teaches a cell culture medium, where the medium contains Dulbecco's Modified Eagle Medium (DMEM), Dulbecco's Modified Eagle Medium: Nutrient Mixture F-12 (DMEM/F12) and/or neurobasal medium (“Cell culture” para 1). The reference teaches that the cell culture medium can be modified by adding one or more factors (same para). The factors can include reduced glutathione, insulin, transferrin, ethanolamine, selenium (i.e., ITS-x) and B27 (see “Neural inducing supplement” para 2). This shows that a cell culture medium containing at least DMEM, ITS, and B27 can also have reduced glutathione, and neurobasal medium as well, reading on “neurobasal medium” as in instant claim 34 in-part and 44 in-part and “reduced glutathione” as in instant claim 44 in-part. Please note that while Nicholas does not teach concentration of neurobasal medium or reduced glutathione are present in the medium, “generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)” (see MPEP 2144.05(II)(A)).
Finally, Haigh teaches that sodium pyruvate is a supplement added to improve cell survival in culture. It teaches that addition of sodium pyruvate improves the cell’s ability to metabolize glucose in the media to produce energy, and while not “necessary” for cell culture, removing it can have negative effects (p. 1 of Haigh). Please note that while Haigh does not teach what concentration of sodium pyruvate should be present in a medium, “generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)” (see MPEP 2144.05(II)(A)).
Therefore, it would have been obvious prior to the effective filing date of the instantly claimed invention to create a cell culture medium as taught by Liu, where the medium contains ITS and trace elements B and C as taught by Chen, to arrive at the instantly claimed invention. Chen shows ITS-X, and trace elements can successfully be added to a culture medium. One of ordinary skill would have been motivated to combine the prior art elements [culture of Liu with components of Chen] according to known methods with a reasonable expectation of advantageously supporting cell viability, proliferation, cloning, and derivation as taught by the prior art. One of ordinary skill in the art would recognize that the improvements caused by the addition of ITS-X and trace elements B and C would improve similar cultures in the same way.
It also would have been obvious prior to the effective filing date of the instantly claimed invention to create a cell culture medium as taught by Liu and Chen in combination, where the medium contains neurobasal medium and reduced glutathione as taught by Nicholas, to arrive at the instantly claimed invention. As Nicholas shows a cell culture medium can contain ITS, reduced glutathione, and neurobasal medium, one of ordinary skill would have been motivated to modify the medium of Liu and Chen in combination with a reasonable expectation of success as taught by the prior art.
Furthermore, it would have been obvious prior to the effective filing date of the instantly claimed invention to create a cell culture medium as taught by Liu, Chen, and Nicholas in combination, where sodium pyruvate is added to the medium as taught by Haigh, to arrive at the instantly claimed invention. As Haigh shows sodium pyruvate is an important supplement to improve cell survival, one of ordinary skill would have been motivated to add any amount of sodium pyruvate in a cell culture medium with a reasonable expectation of advantageously improving a cell’s ability of metabolizing glucose as taught by the prior art.
Response to Arguments
Applicant’s arguments have been fully considered but are not persuasive.
On p. 11-13 of Remarks, Applicant argues that the amendment to claim 30 to recite “porcine expanded potential stem . . . wherein the SRC inhibitor is WH-4-023” and newly added claim 47 to recite “a human expanded potential stem cell . . . wherein the SRC inhibitor is A-419259” and that the specific combination of features provide several unexpected advantages of the mediums described in the prior art. Applicant argues that the lack of the disclosure of the unexpected advantages in the prior art makes the claimed medium non-obvious over the prior art. Applicant argues that the instant application shows that A-419259 has improved properties for human cells while WH-4-023 has improved properties for porcine cells not disclosed or suggested by Liu et al. Applicant argues that the other cited references (Chen, Nicholas, and Haigh) do not the addition of the other elements combined with the medium components disclosed in Liu would result in the unexpected improvement provided by the instant invention.
In response, the examiner disagrees. First, instant claim 30 lists WH-4-023 and A-419259 in the alternative for the “porcine expanded potential stem cell culture medium.” The addition of “porcine expanded potential stem cell” and “human expanded potential stem cell” in claims 30 and 47 merely recite an intended use of the culture medium, and thus, are not limiting (see MPEP 2111.02). In response to applicant's argument that the prior art does not contemplate applicant’s argued unexpected results, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). As per MPEP § 716.02, [a]ny differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). The Liu reference explicitly teaches that the medium containing A-419259 and WH-4-023 is capable of reprogramming human and porcine somatic cells and can be effective to generate pluripotent stem cells from various mammalian species (Summary para 2). It also teaches that stable pig iPSC lines were established using the medium that express robust levels of endogenous key pluripotency genes and minimal levels of lineage marker genes (“PGC Induction, para 3). Fig. 14 shows that EPSCs expressed higher levels of key pluripotency genes including NANOG, TBX3, DPPA3, and KLF4. Thus, applicant’s arguments are not persuasive.
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.
Claim 30-31, 37-38, 44, and 47-50 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 and 4-5 of U.S. Patent No. 10,745,670 B2 in view of Liu et al (WO 2016079146 A1, 17 Nov 2014; 26 May 2016).
Claim 1 of ‘670 recites, inter alia, “A method for producing a population of expanded potential stem cells (EPSCs) which comprises . . . culturing the population in an expanded potential stem cell medium (EPSCM), wherein the EPSCM comprises a basal medium supplemented with inhibitors consisting of an Src Kinases family (SFK) inhibitor, a GSK3 inhibitor and a Tankyrase inhibitor,” Claim 2 of ‘670 recites, inter alia, “wherein the EPSCM further comprises LIF and/or IGF-II,” claim 4 of ‘670 recites, inter alia, “an EPSC maintenance medium comprising one or more of a Ras-ERK inhibitor, a Src Kinase family (SFK) inhibitor, a GSK3 inhibitor and a Tankyrase inhibitor” and claim 5 of ‘670 recites, inter alia, “an EPSC maintenance medium and wherein the EPSC maintenance medium consists of a Src Kinase family (SFK) inhibitor, a GSK3 inhibitor and a Tankyrase inhibitor.”
However, it does not teach that the medium contains vitamin C supplement, ITS-X, trace element B, trace element C, reduced glutathione, and neurobasal medium, sodium pyruvate, or a combination thereof.
Liu teaches production of a population of expanded potential stem cells, requiring culturing the cells in a medium containing one or more of a SRC inhibitor (see claim 1 of Liu). The medium can also contain a basal medium of DMEM/F12, chemically defined lipids, N2, B27; Glutamine-Penicillin- Streptomycin; Non-Essential Amino Acids (i.e., NEAA); vitamin C, LIF and IGF-II (p. 17 line 17; p. 32 lines 21-26). Suitable SRC inhibitors include A-419259, WH-4-023 and Tankyrase inhibitor XAV939 (p. 24 line 1). It can also include 2-mercaptoethanol (i.e., beta-mercaptoethanol), CHIR99021, and IWR-1 (p. 17 line 10; p. 23, line 36; p. 29 line 10-11). The cells are human or porcine (see claim 25 of Liu). The reference further teaches that the medium can contain activin and/or FBS for optimal cell proliferation (p. 29 lines 31-32). It also teaches that the medium can contain an SRK inhibitor such as PP1, PP2, and CGP77675 (p. 25 lines 30-31) as well as serum albumin (i.e., bovine serum albumin which is bovine fraction V) (p. 17, line 18). Liu teaches that the medium can contain DMEM/F12, 100 uM beta-mercaptoethanol (p. 17 line 10), 50 ug/mL vitamin C (p. 71 line 30), NEAA, N2, B27, 5 uM XAV939 (p. 71, line 31), 0.5 to 10 ng/mL LIF (p. 61 line 15-17), activin 1-100 ng/mL and 0.5% FBS (p. 72, line 1), penicillin-streptomycin-glutamine, defined lipids, A419259, CHIR99021, and IWR-1 (also see above 102 rejection). The medium can also contain serum albumin (such as i.e., bovine serum albumin which is bovine fraction V) (p. 17, line 18). The reference further teaches that A419259 is a potent pyridopyrimidine inhibitor of SFKs, XAV939 stabilizes Axon, CHIR99021 promotes metabolic and biosynthetic processes in cells, and LIF enhances ES cells self-renewal and promotes rare totipotent cells (p. 37, lines 24-33). It also teaches that LIF enhances ES cells self-renewal and promotes rare totipotent cells and that activin and FBS optimize cell proliferation (p. 37, lines 24-33). Please note that while Liu does not teach concentration of, e.g., DMEM/F12, A419259, CHIR99021, etc., “generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)” (see MPEP 2144.05(II)(A)).
Chen teaches a fully defined media that supports cell viability, proliferation, cloning, and derivation (abstract). The medium contains water, salts, amino acids, vitamins, glucose, insulin, an FGF, selenium, transferrin (see claim 1 of Chen; ITS is insulin-transferrin-selenium). The medium also contains trace elements B and C (see example 3 of Chen). Please note that while Chen does not teach concentration of ITS or trace elements B and C present in the medium, “generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)” (see MPEP 2144.05(II)(A)).
Nicholas teaches a cell culture medium, where the medium contains Dulbecco's Modified Eagle Medium (DMEM), Dulbecco's Modified Eagle Medium: Nutrient Mixture F-12 (DMEM/F12) and/or neurobasal medium (“Cell culture” para 1). The reference teaches that the cell culture medium can be modified by adding one or more factors (same para). The factors can include reduced glutathione, insulin, transferrin, ethanolamine, selenium (i.e., ITS-x) and B27 (see “Neural inducing supplement” para 2). This shows that a cell culture medium containing at least DMEM, ITS, and B27 can also have reduced glutathione, and neurobasal medium as well, reading on “neurobasal medium” as in instant claim 34 in-part and 44 in-part and “reduced glutathione” as in instant claim 44 in-part. Please note that while Nicholas does not teach concentration of neurobasal medium or reduced glutathione are present in the medium, “generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)” (see MPEP 2144.05(II)(A)).
Finally, Haigh teaches that sodium pyruvate is a supplement added to improve cell survival in culture. It teaches that addition of sodium pyruvate improves the cell’s ability to metabolize glucose in the media to produce energy, and while not “necessary” for cell culture, removing it can have negative effects (p. 1 of Haigh). Please note that while Haigh does not teach what concentration of sodium pyruvate should be present in a medium, “generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)” (see MPEP 2144.05(II)(A)).
Therefore, it would have been obvious for one of ordinary skill prior to the effective filing date to include the additional medium components in the cell culture medium. Thus, the inventions are obvious variants of each other.
Claims 30-31, 37-38, 44, and 47-50 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 11,913,018 B2 in view of Liu et al (WO 2016079146 A1, 17 Nov 2014; 26 May 2016).
Claim 1 of ‘018 recites “An expanded potential stem cell culture medium (EPSCM) comprising a basal cell nutrient medium supplemented with inhibitors consisting of a Src Kinase family (SFK) inhibitor, a GSK3 inhibitor and a Tankyrase inhibitor,” claim 2 of ‘018 recites “An expanded potential stem cell culture medium (EPSCM) comprising a basal cell nutrient medium supplemented with inhibitors consisting of a Src Kinase family (SFK) inhibitor, a GSK3 inhibitor, a Tankyrase inhibitor and one or more of a RAS-ERK inhibitor, a p38 inhibitor and a JNK inhibitor,” claim 3 and 4 of ‘018 recites “the inhibitors consist of a Src Kinase family (SFK) inhibitor, a GSK3 inhibitor, a Tankyrase inhibitor and two or more of a RAS-ERK inhibitor, a p38 inhibitor and a JNK inhibitor”, and claim 5 and 6 of ‘018 recites “the EPSCM further comprises LIF and/or IGF-II.”
However, it does not teach that the medium contains vitamin C supplement, ITS-X, trace element B, trace element C, reduced glutathione, and neurobasal medium, sodium pyruvate, or a combination thereof.
Liu teaches production of a population of expanded potential stem cells, requiring culturing the cells in a medium containing one or more of a SRC inhibitor (see claim 1 of Liu). The medium can also contain a basal medium of DMEM/F12, chemically defined lipids, N2, B27; Glutamine-Penicillin- Streptomycin; Non-Essential Amino Acids (i.e., NEAA); vitamin C, LIF and IGF-II (p. 17 line 17; p. 32 lines 21-26). Suitable SRC inhibitors include A-419259, WH-4-023 and Tankyrase inhibitor XAV939 (p. 24 line 1). It can also include 2-mercaptoethanol (i.e., beta-mercaptoethanol), CHIR99021, and IWR-1 (p. 17 line 10; p. 23, line 36; p. 29 line 10-11). The cells are human or porcine (see claim 25 of Liu). The reference further teaches that the medium can contain activin and/or FBS for optimal cell proliferation (p. 29 lines 31-32). It also teaches that the medium can contain an SRK inhibitor such as PP1, PP2, and CGP77675 (p. 25 lines 30-31) as well as serum albumin (i.e., bovine serum albumin which is bovine fraction V) (p. 17, line 18). Liu teaches that the medium can contain DMEM/F12, 100 uM beta-mercaptoethanol (p. 17 line 10), 50 ug/mL vitamin C (p. 71 line 30), NEAA, N2, B27, 5 uM XAV939 (p. 71, line 31), 0.5 to 10 ng/mL LIF (p. 61 line 15-17), activin 1-100 ng/mL and 0.5% FBS (p. 72, line 1), penicillin-streptomycin-glutamine, defined lipids, A419259, CHIR99021, and IWR-1 (also see above 102 rejection). The medium can also contain serum albumin (such as i.e., bovine serum albumin which is bovine fraction V) (p. 17, line 18). The reference further teaches that A419259 is a potent pyridopyrimidine inhibitor of SFKs, XAV939 stabilizes Axon, CHIR99021 promotes metabolic and biosynthetic processes in cells, and LIF enhances ES cells self-renewal and promotes rare totipotent cells (p. 37, lines 24-33). It also teaches that LIF enhances ES cells self-renewal and promotes rare totipotent cells and that activin and FBS optimize cell proliferation (p. 37, lines 24-33). Please note that while Liu does not teach concentration of, e.g., DMEM/F12, A419259, CHIR99021, etc., “generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)” (see MPEP 2144.05(II)(A)).
Chen teaches a fully defined media that supports cell viability, proliferation, cloning, and derivation (abstract). The medium contains water, salts, amino acids, vitamins, glucose, insulin, an FGF, selenium, transferrin (see claim 1 of Chen; ITS is insulin-transferrin-selenium). The medium also contains trace elements B and C (see example 3 of Chen). Please note that while Chen does not teach concentration of ITS or trace elements B and C present in the medium, “generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)” (see MPEP 2144.05(II)(A)).
Nicholas teaches a cell culture medium, where the medium contains Dulbecco's Modified Eagle Medium (DMEM), Dulbecco's Modified Eagle Medium: Nutrient Mixture F-12 (DMEM/F12) and/or neurobasal medium (“Cell culture” para 1). The reference teaches that the cell culture medium can be modified by adding one or more factors (same para). The factors can include reduced glutathione, insulin, transferrin, ethanolamine, selenium (i.e., ITS-x) and B27 (see “Neural inducing supplement” para 2). This shows that a cell culture medium containing at least DMEM, ITS, and B27 can also have reduced glutathione, and neurobasal medium as well, reading on “neurobasal medium” as in instant claim 34 in-part and 44 in-part and “reduced glutathione” as in instant claim 44 in-part. Please note that while Nicholas does not teach concentration of neurobasal medium or reduced glutathione are present in the medium, “generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)” (see MPEP 2144.05(II)(A)).
Finally, Haigh teaches that sodium pyruvate is a supplement added to improve cell survival in culture. It teaches that addition of sodium pyruvate improves the cell’s ability to metabolize glucose in the media to produce energy, and while not “necessary” for cell culture, removing it can have negative effects (p. 1 of Haigh). Please note that while Haigh does not teach what concentration of sodium pyruvate should be present in a medium, “generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)” (see MPEP 2144.05(II)(A)).
Therefore, it would have been obvious for one of ordinary skill prior to the effective filing date to include the additional medium components in the cell culture medium. Thus, the inventions are obvious variants of each other.
Response to Arguments
Applicant’s arguments have been fully considered but are not persuasive.
On p. 13 of Remarks, Applicant argues that the amendment to claim 30 renders the respective double patenting rejections moot.
In response, the examiner disagrees. The amendments are not sufficient to overcome the newly posited double patenting rejections, and thus, the rejections are proper.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/G.R./Examiner, Art Unit 1632 /KARA D JOHNSON/Primary Examiner, Art Unit 1632