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 .
Status of the Claims
Claims 1, 4, 7-10, 14, 18, and 20-31 are currently pending.
Claims 1, 8, 10, 14, 20, 25, 28, and 29 have been amended.
Claims 1, 4, 7, 22-27, and 30-31 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim.
Claims 2-3, 5-6, 11-13, 15-17, and 19 are cancelled.
Claims 8-10, 14, 18, 20-21, and 28-29 have been considered on the merits.
Withdrawn Rejections
The objection made onto claim 14 has been withdrawn in light of the amendments made on 11/10/2025.
The 35 U.S.C. 112(b) rejections made onto claims 8, 14, 20, and 28 have been withdrawn in light of the amendments made on 11/10/2025.
The 35 U.S.C. 102 rejection has been withdrawn in light of the amendments made on 11/10/2025.
New and Maintained Rejections Necessitated by Amendment
Claim Objections
Claim 28 is objected to because of the following informalities: “the first substratum” in line 2 needs to be amended to “the first culture medium” as presented in claim 8 . Appropriate correction is required.
Claim 8 is objected to because of the following informalities: “Ultraser G” is a misspelling and should be corrected to “Ultroser™ G”, however the term has been previously and is currently rejected under 35 U.S.C. 112(b) for constituting a trademark in the claims. Appropriate correction is required.
Claim 29 is objected to because of the following informalities: “P-mercaptoethanol” should be amended to “b- mercaptoethanol”. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 8-10, 14, 18, 20-21, and 28-29 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 8, 10, 14, and 28 contain the trademark/trade name Ultroser™G. 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 a fetal calf serum replacement and, accordingly, the identification/description is indefinite.
Claims 8, 10, 14, and 28 contain the trademark/trade name KOSR (KnockOut™ Serum Replacement). 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 a fetal bovine serum replacement and, accordingly, the identification/description is indefinite.
Claims 10, 14, and 28 contain the trademark/trade name KO™-DMEM. 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 a basal media optimized for growth of undifferentiated ES cells and, accordingly, the identification/description is indefinite.
Claims 10, 14, and 28 contain the trademark/trade name KO™-DMEM/F12. 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 a low osmolarity basal medium without L-glutamine or HEPES and, accordingly, the identification/description is indefinite.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 8-10, 14, 18, 20-21, and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Brown et al (Cells Tissues Organs, 2009), in view of Meuleman (EU J. Haematology, 2006), Battula et al (Differentiation, 2006), and D’Aniello et al (Stem Cells International, 2017).
Regarding claim 8, Brown teaches a method of producing a population of MSCs through the steps of first culturing pluripotent cells in a first culture media to form embryoid bodies (EBs), the first media comprising a basal medium and a serum replacement, a non-essential amino acids supplement, glutamine, and bFGF (pg. 257, col. 1, para 3-4). Brown teaches that the embryoid bodies are then cultured using a second culture media comprising a basal medium, 4 ng/ml of bFGF, and 10 mM stock solution of non-essential amino acids supplement, which when diluted in the media meets the limitations of “the following amino acids each at a concentration of 0.1 to 0.5 mM: glycine, L-alanine, L-asparagine, L-aspartic acid, L-glutamic acid, L-proline, L-serine” of claim 8 (pg. 257, col. 1, para 3-4).
Regarding claim 9, Brown teaches that the stem cell is a pluripotent stem cell and is an embryonic stem cell (ESC) (pg. 257, col. 1, para 3-4).
Regarding claim 10, Brown teaches that the first medium contains the following characteristics: the amount of bFGF is 4 ng/ml and the base media is DMEM/F12 (pg. 257, col. 1, para 3-4).
Regarding claim 14, Brown teaches that the second medium contains the following characteristics: a growth factor of bFGF and the base media is a-MEM (pg. 257, col. 1, para 3-4).
Regarding claim 18, Brown teaches that the cells in step 1 of claim 8 are cultured in a low attachment culture dish and that the embryoid bodies of step 2 of claim 8 are cultured in a dish coated with gelatin (pg. 257, col. 1, para 3-4).
Regarding claim 20, Brown teaches separating the cells from the gelatin thereby obtaining MSCs (pg. 257, col. 1, para 3-4).
Regarding claim 21, Brown teaches passaging the MSCs (pg. 257, col. 1, para 3-4).
Regarding claim 29, Brown teaches that the first culture medium contains B-mercaptoethanol (pg. 257, col. 1, para 3-4).
Brown does not teach that the second medium contains 1 to 5% Ultroser™ G as required by claim 8. Although Brown teaches the inclusion of L-glutamine in the second medium (pg. 257, col. 1, para 3-4), Brown does not teach that the second medium contains the L-alanyl-L-glutamine at a concentration of 1 to 5 mM as required by claim 8.
However, Meuleman et al teaches about human MSC culture in serum-free media (abstract). Meuleman teaches that their “observations strongly suggest that UC is an optimal medium for ex vivo expansion of MSC: it allows a better cell expansion, preserves cell multipotentiality, reduces the culture period and contains low concentration of serum substitute (abstract).
Regarding claim 8, Meuleman teaches the use of a serum free media supplemented with 2% Ultroser™ G and 2 mM of L-glutamine (pg. 310, col. 1, para 3).
One of ordinary skill in the art prior to the effective filling date of the instant application would find it obvious at the effective filling date of the instant invention to combine the method of Brown with the Ultrosar™ G and L-glutamine concentrations of Meuleman to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Meuleman teaches that their “observations strongly suggest that UC is an optimal medium for ex vivo expansion of MSC: it allows a better cell expansion, preserves cell multipotentiality, reduces the culture period and contains low concentration of serum substitute (abstract). One of ordinary skill in the art would have a reasonable expectation of success when combining Brown with Meuleman because the combination constitutes an optimization of media employed with MSCs.
Brown does not teach that the second medium contains 2 to 20% of KO™SR as required by claim 8.
However, Batttula teaches a method of deriving MSCs from human placenta and bone marrow employing a serum-free medium (abstract). Battula teaches “[u]sing a novel protocol we prepared MSC from BM and non-amniotic placenta (PL) by culture of Ficoll-selected cells in gelatin-coated flasks in the presence of a serum-free, basic fibroblast growth factor (b-FGF)-containing medium that was originally designed for the expansion of human embryonic stem cells (ESC). MSC generated in gelatin-coated flasks in the presence of ESC medium revealed a four-to fivefold higher proliferation rate than conventionally prepared MSC which were grown in uncoated flasks in serum containing medium.” (abstract).
Regarding claim 8, Battula teaches the use of 20% KO™SR in KO-DMEM media for the differentiation of human ESCs into MSCs (pg. 280, last para spanning pg. 281).
One of ordinary skill in the art prior to the effective filling date of the instant application would find it obvious at the effective filling date of the instant invention to combine the method of Brown with the KO™SR taught by Battula to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Battula teaches “[u]sing a novel protocol we prepared MSC from BM and non-amniotic placenta (PL) by culture of Ficoll-selected cells in gelatin-coated flasks in the presence of a serum-free, basic fibroblast growth factor (b-FGF)-containing medium that was originally designed for the expansion of human embryonic stem cells (ESC). MSC generated in gelatin-coated flasks in the presence of ESC medium revealed a four-to fivefold higher proliferation rate than conventionally prepared MSC which were grown in uncoated flasks in serum containing medium.” (abstract). One of ordinary skill in the art would have a reasonable expectation of success when combining Brown with Battula because the combination constitutes an optimization of media employed with MSCs.
Brown does not teach that the second medium contains 1 to 100 µm/ml ascorbic acid as required by claim 8.
However, D’Aniello teaches a review on the use of ascorbic acid (also known as Vitamin C) on cell culture. D’Aniello teaches that “VitC regulates ECM/collagen homeostasis and plays a key role in the differentiation of mesenchymal stem cells towards osteoblasts, chondrocytes, and tendons” (abstract).
Regarding claim 8, D’Aniello teaches that 50 µm/ml of ascorbic acid increases proliferation of MSCs (See Table 1).
One of ordinary skill in the art prior to the effective filling date of the instant application would find it obvious at the effective filling date of the instant invention to combine the method of Brown with the ascorbic acid taught by D’Aniello to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because D’Aniello teaches that “VitC regulates ECM/collagen homeostasis and plays a key role in the differentiation of mesenchymal stem cells towards osteoblasts, chondrocytes, and tendons” (abstract). One of ordinary skill in the art would have a reasonable expectation of success when combining Brown with D’Aniello because the combination constitutes an optimization of media employed with MSCs.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claims 8 and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Brown et al (Cells Tissues Organs, 2009), in view of Meuleman (EU J. Haematology, 2006), Battula et al (Differentiation, 2006), and D’Aniello et al (Stem Cells International, 2017), as applied to claims 8-10, 14, 18, 20-21, and 29 above.
Regarding claim 28, the limitations of the independent claim 8 are taught above.
Regarding claim 28, Brown teaches that the first medium comprises DMEM/F12, KO™SR, nonessential amino acids (includes glycine, L-alanine, L-asparagine, L-aspartate, L-glutamic acid, L-proline, L-serine), L-glutamine, and bFGF (pg. 257, col. 1, para 3-4).
Although Brown teaches that the first basal medium is DMEM/F12, Brown does not teach that the first medium contains the basal medium KO-DMEM as required by claim 28.
However, Batttula teaches a method of deriving MSCs from human placenta and bone marrow employing a serum-free medium (abstract). Battula teaches “[u]sing a novel protocol we prepared MSC from BM and non-amniotic placenta (PL) by culture of Ficoll-selected cells in gelatin-coated flasks in the presence of a serum-free, basic fibroblast growth factor (b-FGF)-containing medium that was originally designed for the expansion of human embryonic stem cells (ESC). MSC generated in gelatin-coated flasks in the presence of ESC medium revealed a four-to fivefold higher proliferation rate than conventionally prepared MSC which were grown in uncoated flasks in serum containing medium.” (abstract).
Regarding claim 28, Battula teaches the use of KO-DMEM media supplemented with 20% KO™SR, L-glutamine, nonessential amino acids, and bFGF for the differentiation of human ESCs into MSCs (pg. 280, last para spanning pg. 281).
One of ordinary skill in the art prior to the effective filling date of the instant application would find it obvious at the effective filling date of the instant invention to combine the method of Brown with the KO-DMEM taught by Battula to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Battula teaches “[u]sing a novel protocol we prepared MSC from BM and non-amniotic placenta (PL) by culture of Ficoll-selected cells in gelatin-coated flasks in the presence of a serum-free, basic fibroblast growth factor (b-FGF)-containing medium that was originally designed for the expansion of human embryonic stem cells (ESC). MSC generated in gelatin-coated flasks in the presence of ESC medium revealed a four-to fivefold higher proliferation rate than conventionally prepared MSC which were grown in uncoated flasks in serum containing medium.” (abstract). One of ordinary skill in the art would have a reasonable expectation of success when combining Brown with Battula because the combination constitutes an optimization of media employed with MSCs.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant argues, regarding the rejections of claims 8, 10, 14, and 28 under 112(b), that the trademarks present in the claims “have been widely accepted by those skilled in the art to refer to defined culture medium components, for which no generic names exist”.
In response, the argument is not found persuasive. 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 pre-AIA 35 U.S.C. 112, 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. Therefore, the arguments are not found persuasive.
Applicant’s arguments, see Remarks, filed 11/10/2025, with respect to the rejection(s) of claim(s) 8-10, 14, 18, 20-21, and 28-29 under 35 U.S.C. 102 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Brown et al (Cells Tissues Organs, 2009), in view of Meuleman (EU J. Haematology, 2006), Battula et al (Differentiation, 2006), and D’Aniello et al (Stem Cells International, 2017).
Conclusion
No claims are 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CONSTANTINA E STAVROU whose telephone number is (571)272-9899. The examiner can normally be reached M-F 8:00-5:00.
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CONSTANTINA E. STAVROU
Examiner
Art Unit 1632
/ANOOP K SINGH/Primary Examiner, Art Unit 1632