DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 5/18/2026 has been entered.
Claim Status
As of the Final Office Action mailed 12/16/2025, claims 30-31 and 35-50 were pending and claims 35-36, 39-43, and 45-46 were withdrawn for being drawn to nonelected invention.
In Applicant's Response filed on 5/18/2026, claims 30-31 and 37 were amended and claims 44 and 47-50 were canceled.
As such, claims 30-31, 35-43, and 45-46 are pending and claims 30-31 and 37-38 have been examined herein.
Withdrawn Objections/Rejections
The objections and rejections presented herein represent the full set of objections and rejections currently pending in this application. Any objections or rejections not specifically reiterated are hereby withdrawn.
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 and 37-38 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 expanded potential stem cells are human or porcine (see claim 25 of Liu) (“wherein the cell culture medium is sufficient to support growth of a population porcine expanded potential stem cells” as in instant claim 30 in-part). 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). 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 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. 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). 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). 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 and 38). 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). Please note that while Chen does not teach concentration of ITS-X 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” and “reduced glutathione” as in instant claim 30 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 filed 5/18/2026 have been fully considered but they are not persuasive. On p. 9-11 of Remarks, Applicant argues, in sum, that neither Chen, Nicholas, nor Haigh does not teach or suggest supporting growth of porcine expanded potential stem cells. Applicant also argues that the Haigh reference is “a networking site for scientists and researchers to ask questions and collaborate with one another. As such, the purported teaching in Haigh is merely one user's answer to another user's question on the site . . . there is no way to verify the accuracy of the assertion made by Haigh on this website, let alone determine whether it has any connection with the teachings of the presently claimed cell culture medium.” Applicant also argues that one of ordinary skill in the art would not rely on or be motivated by a two sentence post to incorporate sodium pyruvate into the medium of Liu. Finally, Applicant argues that the present application demonstrates that WH-4-023 has improved properties for porcine cells.
In response, the examiner disagrees. First, the applicant note that the Liu reference already states that a medium containing SRC inhibitor, 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, activin and/or FBS is sufficient to culture both human and porcine expanded potential stem cells as instantly claimed. The Liu reference also states that WH-4-023 can be used for in the culture medium. "Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Moreover, “wherein the cell culture medium is sufficient to support growth of a population porcine expanded potential stem cells” as recited in instant claim 30 is an intended use of the culture medium (see MPEP 2111.04). All the references provided provide a reasonable teaching, suggestion, or motivation to include particular medium components, what purpose they serve, etc. Thus, one of ordinary skill in the art would have been motivated prior to the effective filing date to combine the instantly claimed medium components to create a culture medium. Finally, regarding the Haigh reference, the examiner reminds Applicant that one of ordinary skill in the art has access to any and all references that are relevant to claims, including but not limited to, published papers, blog post, forums, YouTube, social media posts (i.e., X, Facebook, etc.), images, books, magazine, press releases, conference abstracts, research posters, etc. All of the examples listed above qualify as “printed publications” as they are accessible to the public. A reference is proven to be a "printed publication" "upon a satisfactory showing that such document has been disseminated or otherwise made available to the extent that persons interested and ordinarily skilled in the subject matter or art, exercising reasonable diligence, can locate it." In re Wyer, 655 F.2d 221, 210 USPQ 790 (CCPA 1981) (quoting I.C.E. Corp. v. Armco Steel Corp., 250 F. Supp. 738, 743, 148 USPQ 537, 540 (SDNY 1966)). An electronic publication, including an online database or Internet publication (e.g., discussion group, forum, digital video, or social media post), is considered to be a "printed publication" within the meaning of 35 U.S.C. 102(a)(1) and pre-AIA 35 U.S.C. 102(a) and (b) provided the publication was accessible to persons concerned with the art to which the document relates. See In re Wyer, 655 F.2d 221, 227, 210 USPQ 790, 795 (CCPA 1981); see MPEP 2128(I)(A) and (II)(A). Finally, an electronic publication, like any publication, may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art (MPEP 2128(II)(C)). 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), 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).
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 and 37-38 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), 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).
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 expanded potential stem 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. 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 posited double patenting rejections. The amendment to recite the intended use limitation of “wherein the cell culture medium is sufficient to support growth of a population porcine expanded potential stem cells” in claim 30 is taught in cited reference Liu. Thus, the rejections are proper.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GILLIAN C REGLAS whose telephone number is (571)270-0320. The examiner can normally be reached M-F 9-5.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras Jr can be reached at (571) 272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/G.R./Examiner, Art Unit 1632 /KARA D JOHNSON/Primary Examiner, Art Unit 1632
Prosecution Insights