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 .
Applicant’s response on 11/20/2025 has been received and entered. Claims 1-12 and 14 are pending, all of which have been considered on the merits.
Claim Interpretation
Claim 1 is drawn to a process comprising five steps. For ease of reference throughout this office action, these steps will be referred to as “Steps 1-5”.
Status of Prior Rejections/Response to Arguments
RE: Rejection of claims 1-13 under 35 U.S.C. 112(a)
Applicants have amended claim 1 to define the first medium as E8, the second medium as E6, and the third medium as a serum free mesenchymal stem cell medium. However, the amendments do not sufficiently describe the claimed method. See rejection below.
The rejection over claims 1-12 is maintained.
Claim 13 has been cancelled rendering the rejection moot.
RE: Rejection of claim 13 under 35 U.S.C. 101
Claim 13 has been cancelled rendering the rejection moot.
RE: Rejection of claim 13 under 35 U.S.C. 102 over Kwon et al (Scientific Reports, 2016)
Claim 13 has been cancelled rendering the rejection moot.
RE: Rejection of claim 13 under 35 U.S.C. 102 over Wang et al (US9725698B2)
Claim 13 has been cancelled rendering the rejection moot.
RE: Rejection of claims 1, 2, 4-8, and 11-13 under 35 U.S.C. 103 over Wang et al (US9725698B2) in view of Lee et al (Human Reproduction, 2015)
Applicants traverse the rejection of record on the grounds that the mediums of Wang et al and Lee et al are not known to be interchangeable because the mediums are used for a different purpose.
In response, the argument has been fully considered but is not convincing. Wang et al teaches a method comprising a step of differentiating ESCs to trophoblasts in culture medium. Lee et al teaches using a culture medium, from a previously published protocol, for differentiating ESC lines to trophoblastic cells (See Sec. Differentiation to trophoblastic cells). Thus the mediums of Wang et al and Lee et al are used for the same purpose. Given that Lee discloses the medium is from a previously published protocol, it would have been known in the art that the medium of Lee et al could be used to differentiate ESCs to trophoblasts.
Additionally, applicants amended the claims to require Essential 8 (E8) medium as the first medium, Essential 6 (E6) medium as the second medium, and PD173074 as the FGFR3 inhibitor.
Neither Want et al or Lee et al teach a method comprising E8 or E6 medium.
The rejection over claims 1, 2, 4-8, and 11-12 is withdrawn.
Claim 13 has been cancelled rendering the rejection moot.
RE: Rejection of claims 1-13 under 35 U.S.C. 103 over Wang et al (US9725698B2) in view of Lee et al (Human Reproduction, 2015) and Maldonado et al (Stem Cell Research, 2016)
Applicants traversed the rejection of record on the grounds that Maldonado et al discloses Rock inhibitors to prevent apoptosis of pluripotent cells whereas the instant application uses a Rock inhibitor as part of the process of forming the claimed perinatal mesenchymal stem cells.
In response, the argument has been considered but is not persuasive. 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). While Maldonado et al teaches including Rock inhibitors for a different purpose than the instant application, prevention of apoptosis is a desirable effect and thus a person of ordinary skill in the art would be motivated to include ROCK inhibitors in their culturing method in order to prevent apoptosis.
Applicants amendments to the claims, requiring E8 as the first medium and E6 as the second medium overcome the rejection of record.
The rejection over claims 1-12 is withdrawn.
Claim 13 has been cancelled rendering the rejection moot.
New/Maintained Rejections
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-12 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Independent claim 1 is drawn to a method of differentiating iPSCs to perinatal MSC-like cells with an intermediate step of differentiating the cells to induced hiPS trophoblasts. The method of claim 1 requires steps of culturing hiPSCs in a E8 for a first predetermined period of time to form hiPS trophoblasts followed by steps of differentiating the hiPS trophoblasts in a E6 for a second time period, differentiating the hiPS trophoblasts in a serum-free mesenchymal stem cell medium for a third time period, then further differentiating the hiPS trophoblasts in serum free mesenchymal stem cell medium for a third predetermined period of time a predetermined number of times to produce the perinatal MSC-like cells.
The issue at hand is the scope of the differentiation method of claim 1, and particularly whether or not Applicants were in possession of the full scope of the claimed step.
The Specification discloses exactly one method for differentiating the iPSCs to MSC-like cells: step 1) Culturing hiPSCs in E8 medium for two days, step 2) changing the media to E6 differentiation media comprising BMP4, an ALK5 inhibitor, and an FGFR3 inhibitor, and culturing for four days, step 3) replating the cells, step 4) culturing the cells in StemPro MSC SFM CTS differentiating medium for 6 days, and step 5) passaging the cells every six days (See ¶0024-0026 and Fig. 1).
The claims however are not limited to this specific embodiment. Rather, the claim scope includes any method for differentiating iPSCs to perinatal MSC-like cells comprising an intermediate cell type of trophoblasts and comprising steps (1-5) of culturing in E8 medium, E6 medium, and serum-free mesenchymal stem cell medium, performing each culturing step for any amount of time, and further comprising steps of replating cells and culturing for a predetermined number of times(step 6). While the first, second, and third mediums have been generally defined, the steps of the method are broad allowing for culturing in each of the mediums for any period of time and the last culturing step can be performed any number of times. Additionally, while steps requiring “differentiating the amount of human induced pluripotent stem trophoblasts” are recited, there is no indication of what the cells are being differentiated to and thus can include differentiating the cells to any cell type or rather maintaining the cells without differentiating them.
This is a situation where a broad claim (in this case, a broad step in a claim) is presented, but the disclosure only describes a narrow species with no evidence that the full genus was contemplated. In such cases, a holding of lack of written description is proper See MPEP 2163.03(V). Disclosure of a single method within the broad claim scope does not provide written description for the full scope of the claim. The single disclosed method cannot be held to be representative of all methods covered by the claims. Nor does the instant disclosure identify any particular feature of the exemplified method as critical or essential, such that one could determine variations which would also satisfy the requirements (note: if any feature or step is critical or essential, it must be recited in the claims, otherwise this amounts to omission of an essential step). Therefore, claims 1-12 are rejected as failing to comply with the written description requirement because the original disclosure does not support that Applicants were in possession of the full genus of methods of differentiating iPSCs to perinatal MSC-like cells via an intermediate step of hiPS trophoblasts.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-12 and 14 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 1 contains the trademark/trade names Essential 8 and Essential 6. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe cell culture mediums and, accordingly, the identification/description is indefinite. Claims 2-12 and 14 depend from claim 1 and thus inherit the deficiency of claim 1.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 2 and 7 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Regarding claim 2: Claim 2 requires the limitation of “wherein the first medium comprises a stem cell culture medium”. Claim 1 defines the first medium as a medium comprising Essential 8 medium. Essential 8 medium is a stem cell culture medium (See Gibco, pg. 2). Thus, claim 2 fails to further limit claim 1.
Regarding claim 7: Claim 7 requires the limitation of “wherein the third medium comprises a serum-free medium”. However, claim 1 already defines the third medium as a medium comprising a serum-free mesenchymal stem cell medium. Thus, claim 7 does not further limit claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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 1, 2, 4-8, 11-12, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al (US9725698B2) in view of Hori et al (Curr Protoc Stem Cell Biol, 2019), Wei et al (Placenta, 2017), and Gibco (Essential 8 media systems Brochure, 2018).
Wang et al teaches a method of producing human trophoblast derived mesenchymal stem cells (T-MSCs) from hESCs or iPSCs (See abstract and claim 1). The method comprises culturing the hESCs until 80% confluent in mTESR1 media (See claim 2 and Col. 56, lns 44-49. Next, the hESC or iPSCs were cultured in media comprising BMP-4 and a TGFß inhibitor such as an ALK5 inhibitor, for 1-5 days to differentiate the cells into trophoblasts (See claim 1a, Fig. 1, and Col. 4, lns 38-47). The trophoblasts were dissociated then plated and cultured for 4-10 days in mesenchymal stem cell growth media to produce the T-MSCs (See claim 1c, Fig. 1, and Col. 4, lns 54-65. The MSC growth media can contain serum or be serum free (See Col. 4, lns 54-65). The T-MSCs produced by the method of Wang et al express CD73, CD105, and CD90 (See Col. 5, lns 3-4).
Regarding claims 1, 2, 7, and 11: Wang et al teaches a method of producing T-MSCs from hESCs or iPSCs which reads on a method of forming non-naturally occurring cells that exhibit the characteristics of naturally occurring perinatal mesenchymal stem cells. For purposes of this rejection the method of Wang et al can be characterized as:
culturing hESCs to 80% confluency in mTESR1,
splitting the cells,
differentiating the hESCs or iPSCs to trophoblasts in media comprising serum-free media, BMP-4 and an ALK5 inhibitor for 1-5 days,
dissociating the trophoblasts,
replating into MSC growth medium, and
culturing the trophoblasts in the MSC growth medium for 4-10 days to differentiate into T-MSCs (letterettes added by Examiner).
This method is comparable to the method of claim 1 as follows:
Step (c) of Wang et al is comparable to steps 1-2 of claim 1. Specifically the serum-free medium reads on both ‘a first medium’ and ‘a second medium comprising an amount of ALK5 inhibitor and an amount of BMP4. The ‘first period of time’ can be considered any portion of the 1-5 days, and the ‘second period of time’ can be considered the remainder of the portion of 1-5 days.
Steps (d)-(e) of Wang et al reads on step 3 of claim 1. The MSC growth medium reads on ‘a third medium’.
Step (f) of Wang et al reads on step 4 of claim 1. The period of 4-10 days reading on ‘a third period of time’.
Wang et al differs from the instant claim in that (i) Wang et al exemplifies culture of ESCs, not iPSCs, (ii) Wang et al does not teach additional replating steps following differentiation to T-MSCs (i.e. step 5 of the instant method), (iii) Step (c) of Wang et al does not include culturing in a first medium that is Essential 8 medium and a second medium that is Essential 6 medium, and (iv) the media of Wang et al used in step (c) does not comprise an FGFR3 inhibitor.
Regarding (i), although Wang et al does not exemplify culturing the iPSCs in a medium, Wang does teach an exemplary embodiment in which hESCs are differentiated to trophoblasts comprising steps equivalent to the first two steps of the instant application. Wang et al further teaches either hESCs or iPSCs can be used for the disclosed method. Therefore, it would have been prima facie obvious to substitute the hESCs in the trophoblast differentiation steps of Want et al, with iPSCs. One would have expected the iPSCs to work equivocally with hESCs in the method of Wang et al because Wang et al teaches either cell can be used as the starting cell type. Additionally, culturing iPSCs in mTESR1 media is a known technique in the art. Substitution of one element for another known in the field, wherein the result of the substitution would have been predictable is considered to be obvious. See KSR International Co. V Teleflex Inc 82 USPQ2d 1385 (US2007) at page 1395.
Regarding (ii), Wang et al does not teach additional replating steps, however, it would have been prima facie obvious to a person of ordinary skill in the art to optimize the number of times the cells were replated in order to further differentiate the cells or split cells which have become confluent. Where 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 (See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (MPEP 2144.05)). Therefore, performing additional replating steps following differentiation of the T-MSCs in order to expand and maintain the T-MSCs would have been prima facie obvious. These additional replating steps read on step 5 of claim 1.
Regarding (iii and iv) Step (c) of Wang et al comprises culturing in a serum free medium, however the specific medium is not defined. Hori et al teaches human pluripotent stem cells can be differentiated to trophoblasts in E8 medium (See abstract and Sec. Anticipated Results). Gibco teaches Essential 8 (E8) is a pluripotent stem cell medium (See pgs. 2 and 4) Gibco further teaches E8 medium can be used in a workflow with Essential 6 (E6) medium for differentiation and reprogramming (See pg. 4). Wei et al teaches a method of differentiating iPSCs or human ESCs to trophoblasts by culturing the stem cells in E6 medium comprising 10 ng/ml BMP4, 1 μΜ A83-01 and 0.1 μΜ PD173074 (See Sec. 2.4 ESCs and iPSCs differentiation).
Given that Wang et al discloses differentiating stem cells to trophoblasts in a serum free medium and Hori et al teaches E8 medium can be used for differentiating hPSCs to trophoblasts, it would have been prima facie obvious to substitute the serum-free medium in step (c) of Wang et al with E8 medium. One would have expected the E8 medium to work equivocally with the serum-free medium of Wang et al in the method of Wang et al because E8 is a serum free medium for culturing pluripotent stem cells. Substitution of one element for another known in the field, wherein the result of the substitution would have been predictable is considered to be obvious. See KSR International Co. V Teleflex Inc 82 USPQ2d 1385 (US2007) at page 1395.
Furthermore, it would have been prima facie obvious to transition the cells from the E8 medium to the E6 medium of Wei et al which comprises PD173074, during step (c) based on Gibco’s teachings that E8 and E6 mediums can be used in a workflow for differentiation of pluripotent stem cells. One would have been motivated to modify step (c) of Wang et al because Gibco teaches E8 and E6 mediums can be used together in a workflow for differentiation of pluripotent stem cells. There is a reasonable expectation of success because Wei et al teaches an E6 formulation for differentiating stem cells to trophoblasts.
Regarding claim 4: Following the discussion of claim 1 above, days 1-2 (two days) of step (c) of Wang et al can be considered to read on the ‘first period of time’.
Wang et al does not teach culturing the cells for two days.
Although Wang et al does not teach culturing the cells for two days, it would have been prima facie obvious to optimize the length of time for which the cells are cultured, and split the cells after two days, in order to reach the optimal confluency of cells for further experimental steps. Where 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 (See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (MPEP 2144.05)).
Regarding claim 5: Following the discussion of claim 1 above, Wang et al teaches a medium for differentiating hESCs/iPSCs to trophoblasts. Given that it would have been obvious to split the cells during culturing (see rejection of claims 1 and claim 4 above). It would have been obvious to further culture the cells in the same media. Wang et al further teaches TGFβ inhibitors (SB431542 (1-20 μM), A83-01 (0.2-5 μM) or ALK5 inhibitor (1-20 μM), etc.) can be used to increase the trophoblast forming efficiency (See Col. 15 lns 10-13).
Wang et al does not disclose the second medium comprises a ratio of 10 μM of an Alk-5 inhibitor to 10ng/ml of BMP-4 to 0.1 μM of an FGFR3 inhibitor.
Wei et al teaches a medium for differentiating hESCs to trophoblasts comprising 10 ng/ml BMP4, 1 μM A83-01 (ALK5 inhibitor), and 0.1 μM PD173074 (FGFR3 inhibitor) (See pg. 2615, Sec. Differentiation to trophoblastic cells. Modifying step (c) of Wang et al to include culturing in the medium of Wei et al is obvious. (See rejection of claim 1 above).
Given that Wang et al teaches TGFß inhibitors can be used to increase trophoblast forming efficiency, it would have been prima facie obvious to optimize the amount of A83-01 to arrive at the claimed amount of 10 μM in order to improve trophoblast forming efficiency. Where 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 (See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (MPEP 2144.05)).
Regarding claim 6: Following the discussion of claim 1 above, days 2-5 (four days) of step (c) of Wang et al can be considered to read on the ‘second period of time’.
Regarding claims 8: Following the discussion of claim 1 above, Wang et al discloses the MSC growth media (reads on a third medium and a medium that encouraged growth and expansion of human MSCs) can be serum free.
Regarding claim 12: Following the discussion of claim 1 above, steps (d)-(e) of Wang et al involves replating PSC-derived trophoblasts.
Wang et al does not disclose replating the PSC-derived trophoblasts at a seeding density of 1:5.
Although Wang et al does not disclose replating the PSC-derived trophoblasts at a density of 1:5, it would have been prima facie obvious to a person of ordinary skill in the art to optimize the seeding density of the cells based on how quickly the cells grow. Where 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 (See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (MPEP 2144.05)).
Regarding claim 14: Following the discussion of claim 1 above, Following the discussion of claim 1 above, days 1-2 (two days) of step (c) of Wang et al can be considered to read on the ‘first period of time’, days 2-5 (four days) of step (c) of Wang et al can be considered to read on the ‘second period of time’, and step (f) which comprises 4-10 days reads on the third time period.
Wang et al does not teach the first time period is two days, the second time period is four days, and the third time period is six days.
Although Wang et al does not teach culturing the cells for two, four, and six days, it would have been prima facie obvious to optimize the length of time for which the cells are cultured, and split the cells after two, four, and six days, in order to reach the optimal confluency of cells for further experimental steps. Where 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 (See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (MPEP 2144.05)).
Claims 1, 2, 4-8, 11-12, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al (US9725698B2) in view of Hori et al (Curr Protoc Stem Cell Biol, 2019), Wei et al (Placenta, 2017), Gibco (Essential 8 media systems Brochure, 2018), and Maldonado et al (Stem Cell Research, 2016).
The teachings of Wang et al, Hori et al, Wei et al, and Gibco et al are set forth above.
Wang et al in view of Hori et al, Wei et al, and Gibco render claims 1, 2, 4-8, 11-12, and 14 obvious.
Regarding claim 3: Following the discussion of claim 1 above, Wang et al teaches a method of producing T-MSCs from hESCs/iPSCs comprising culturing hESCs in a first medium.
Wang et al does not teach the first medium comprises a rock inhibitor.
Maldonado et al teaches ROCK inhibitors prevents dissociation induced apoptosis of human pluripotent stem cells (See pg. 222, last paragraph).
Given that Wang et al teaches a method comprising culturing pluripotent stem cells in a first medium and Maldonado et al teaches ROCK inhibitors prevent apoptosis of pluripotent stem cells, it would have been prima facie obvious to add a ROCK inhibitor to the first medium of Wang et al. One would have been motivated to modify the first medium of Wang et al by adding a ROCK inhibitor because Maldonado et al teaches ROCK inhibitors prevent apoptosis of pluripotent stem cells. There is a reasonable expectation of success because Wang et al teaches a method of culturing pluripotent stem cells.
Regarding claim 9: Following the discussion of claim 1 above, Wang et al teaches a method of producing T-MSCs from hESCs/iPSCs comprising differentiating cells to MSCs in a third medium.
Wang et al does not teach the third medium comprises a rock inhibitor.
Maldonado et al teaches ROCK inhibitor Y-27632 promotes differentiation of iPSCs into mesoderm lineages (See pg. 222, last paragraph).
Given that Wang et al teaches a method comprising differentiating iPSCs to T-MSCs in a third medium and Maldonado et al teaches ROCK inhibitors Y-27632 promotes differentiation of iPSCs into mesoderm lineages, it would have been prima facie obvious to add a ROCK inhibitor to the third medium of Wang et al. One would have been motivated to modify the third medium of Wang et al by adding a ROCK inhibitor because Maldonado et al teaches Y-27632 promotes differentiation of iPSCs into mesoderm lineages. There is a reasonable expectation of success because the MSCs are cells of mesoderm lineage.
Regarding claim 10: Following the discussion of claims 1 and 9 above, Wang et al teaches differentiating cells to MSCs comprising a step of culturing for a third time period of 4-10 days.
Wang et al does not teach the third time period is six days.
Although Wan et al does not teach culturing for a third time period of six days, it would have been prima facie obvious to optimize the length of time for which the cells are cultured, and arrive at the claimed length of six days, in order to reach a desired percentage of cells which have differentiated to MSCs. Where 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 (See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (MPEP 2144.05)).
Conclusion
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 MARISOL A O'NEILL whose telephone number is (571)272-2490. The examiner can normally be reached Monday - Friday 7:30 - 5:00 EST.
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/MARISOL ANN O'NEILL/Examiner, Art Unit 1633
/ALLISON M FOX/Primary Examiner, Art Unit 1633