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 amendments to the claims and arguments filed on 06-25-2025 have been received and entered. Claims 4, 17 have been amended. Claims 18, 20, 22, 24-29 have been canceled. Claims 30-31 have been amended. Claims 1-17, 19, 21, 23, 30-31 are pending.
Election/Restrictions
Applicant’s election without traverse of Group I (Claims 1-17, 19, 21) in the reply filed on 03-21-2025 is acknowledged.
Claim 23 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected subject matter, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 03-21-2025.
Claims 1-17, 19, 21, 30-31 are under consideration.
Priority
This application is a 371 of PCT/US2022/079651 filed on 11/10/2022 that claims priority from US provisional application 63/278,902 filed on 11/12/2021.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 06-25-2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Withdrawn-Claim Rejections - 35 USC § 112
Claim 17 was 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. In view of Applicant's amendments to claim 17 deleting the limitation “optionally wherein the activator of the WNT signaling pathway is GSK3 inhibitor, preferably CHIR99021 and/or wherein the activator of SHH is Smoothened Agonist (SAG) ” obviates the basis of the rejection. Applicants' arguments with respect to the withdrawn rejections are thereby rendered moot.
Claim Objections
Claims 17 and 31 are objected to because of the following informalities:
Claims 17 and 31 are objected as being incomplete in term of limitations. There is no period “.” at the end of the claims (see below). For the sake of compact prosecution, these two claims are interpreted as having period “.” at the end of the claims.
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Appropriate correction is required.
Maintained and new - Claim Rejections - 35 USC § 103- Necessitated by amendments
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.
Claims 1-6, 9-17, 19, 21, 30-31 are rejected under 35 U.S.C. 103 as being unpatentable over Studer et al (Pub.. No .: US 2022/0177835 A1, Provisional application No. 62/893,674 , filed on Aug. 29, 2019) in view of Mahato et al (Movement Disorders, Vol. 35, No. 2, 2020, DOI: 10.1002/mds.27943) as evidenced by Technical Resources (Thermo Fisher Scientific - US https://www.thermofisher.com/us/en/home/technical-resources/media-formulation.251.html, Wayback machine date: 2018).
Claim interpretation:
The specification of the claimed invention teaches that an induced neuronal precursor cell for use according to the methods described herein is obtained by culturing a mammalian pluripotent cell in a neural induction medium for a time suitable to produce the induced neuronal precursor cell ([0020], page 2). Thus, induced neuronal precursor cell (iNPC) is interpreted as cells obtained by culturing a mammalian pluripotent cell in a neural induction medium.
Regarding to claims 1-2, Studer et al teach an in vitro method for inducing differentiation of stem cells to obtain a population of differentiated cells expressing at least one marker indicating a midbrain dopamine neuron or a precursor thereof ([0007], page 1). The stem cells are induced pluripotent stem cells ([0030], page 2). The method further comprises subjecting the population of differentiated cells to conditions favoring differentiation of midbrain dopamine neuron precursors to midbrain dopamine neurons ([0028], page 2). Differentiation of mDA Precursors to mDAs: the cells are contacted with DA neuron lineage specific activators and inhibitors, for example, glial cell -derived neurotrophic factor (GDNF) ([0191], page 14).
Although Studer et al teach GDNF, Studer et al do not teach GDNF receptor RET agonist. However, Mahato et al cure the deficiency. Mahato et al teach glial cell line–derived neurotrophic factor receptor rearranged during transfection agonist supports dopamine neurons in vitro and enhances dopamine release in vivo (title). Mahato et al teach GDNF receptor RET agonist, BT13, that support the survival of cultured dopamine neurons, protect cultured dopamine neurons against neurotoxin-induced cell death, activate intracellular signaling pathways both in vitro and in vivo, and regulate dopamine release in the mouse striatum as well as BT13’s distribution in the brain (Abstract). Midbrain neuron cultures were prepared and treated with 1 μM of BT13 (Page 247, left column, 3rd para).
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the rejected claims to combine the teachings of prior art to modify the method of Studer et al by using DA neuron lineage specific activators such as GDNF receptor RET agonist, BT13, as taught by Mahato et al as instantly claimed, with a reasonable expectation of success. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would be motivated to do so as Mahato et al provide explicit advantage of using BT13 such as supporting the survival of cultured dopamine neurons, protecting cultured dopamine neurons against neurotoxin-induced cell death, activating intracellular signaling pathways both in vitro and in vivo, and regulating dopamine release in the mouse striatum (Abstract). One of ordinary skill in the art would have had a reasonable expectation of success in doing so because Mahato et al provides proof of principle for using GDNF receptor RET agonist such as BT13 in cell culture to support the survival of cultured dopamine neurons.
Regarding to claim 3, Mahato et al teach Figure 1J showing the use of BT13 in concentration of 0.1-50 µM (Page 248, see below). Thus, a person of ordinary skill in the art would be able to use a range of BT13 concentration from 0.1-50 µM to optimize the cell culture.
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Regarding to claim 4, Mahato et al teach the use of BT13 or GDNF : Analysis of pERK and pS6 levels in the mouse brains treated with BT13 or GDNF (Page 247 left column, 4th para.). Thus, it is a matter of choice for a person of ordinary skill in the art to choose between BT13 or GDNF.
Regarding to claim 5, Studer et al teach the described activators are added to a cell culture medium comprising the cells . Suitable cell culture media include Neurobasal medium ([0182], page 13). The Neurobasal medium is essentially free of proteins as evidenced by Technical Resources.
Regarding to claim 6, Studer et al teach suitable cell culture media include N2 medium , B-27 medium, and combinations thereof ([0182], page 13).
Regarding to claim 9-10, Studer et al teach that the methods further comprise contacting the cells with midbrain DA lineage specific activators and inhibitors, for example, cAMP and/or DAPT ([0143], page 7).
Regarding to claim 11, Studer et al teach the cells are contacted with the foregoing DA neuron lineage specific activators and inhibitors for at least at least about 10 or more days ([0191], page 14)
Regarding to claim 12-13, Studer et al teach methods of generating and isolating midbrain dopamine neurons (Title).
Regarding to claim 14, Studer et al teach the method comprises obtaining a cell population of the differenced cells , wherein at least about 90% of the differentiated cells express at least one marker indicating a mDA or a mDA precursor such as tyrosine hydroxylase (TH) ([0185], page 13, and also see Figure 12)
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Regarding to claim 15-16, Studer et al teach the at least one inhibitor of SMAD signaling is inhibitors of bone morphogenetic protein (BMP) signaling ([0016], page 1). The at least one inhibitor of BMP signaling comprises LDN193189 , Noggin, dorsomorphin, a derivative thereof, or a mixture thereof ([0019], page 2).
Regarding to claim 17, Studer et al teach the at least one activator of Wnt signaling is selected from CHIR99021 ([0021], page 2).
Regarding to claim 19, Studer et al teach the at least one inhibitor of SMAD signaling is selected from inhibitors of TGFβ/Activin -Nodal signaling ([0016], page 1). The at least one inhibitor of TGFβ/Activin -Nodal signaling comprises SB431542 , or a derivative, or a mixture thereof ([0018], page 2).
Regarding to claim 21, Studer et al teach methods of generating and isolating midbrain dopamine neurons (Title) (for the preamble). Studer et al provides an in vitro method for inducing differentiation of stem cells to obtain a population of differentiated cells expressing at least one marker indicating a midbrain dopamine neuron (mDA) or a precursor thereof ([0007], page 1). The stem cells are induced pluripotent stem cells ([0030]) (for claim 21, step (i)). Studer et al teach the method further comprises subjecting the population of differentiated cells to conditions favoring differentiation of midbrain dopamine neuron precursors to midbrain dopamine neurons ([0028], page 2). the methods further comprise contacting the cells with midbrain DA lineage specific activators and inhibitors, for example, BDNF, GDNF, CAMP, TGFB , ascorbic acid (AA ), and /or DAPT, to induce differentiation of mDA precursors to mDAs ([0143], page 7). As described above, although Studer et al teach GDNF, Studer et al do not teach GDNF receptor RET agonist. Mahato et al teach Midbrain neuron cultures were prepared and treated with 1 μM of BT13 (Page 247, left column, 3rd para), and BT13 (GDNF receptor RET agonist) support the survival of cultured dopamine neurons, protect cultured dopamine neurons against neurotoxin-induced cell death, activate intracellular signaling pathways both in vitro and in vivo, and regulate dopamine release in the mouse striatum as well as BT13’s distribution in the brain (Abstract). Thus, One of ordinary skill in the art would be motivated to replace GDNF with GDNF mimetics compound such as BT13 to support the survival of cultured dopamine neurons (for claim 21, step (ii)).
Regarding to claim 30, Studer et al teach that in certain embodiments, the at least one Wnt activator lowers GSK3β for activation of Wnt signaling. Thus, in certain embodiments, the Wnt activator is a GSK3β inhibitor. A GSK3P inhibitor is capable of activating a WNT signaling pathway ([0156], page 9). In certain embodiments, the at least one activator of SHH signaling is selected from SHH protein, Smoothened agonists (SAG) , derivatives thereof, and mixtures thereof ([0022], page 2).
Regarding to claim 31, Studer et al teach that the at least one Wnt activator is a small molecule selected from CHIR99021 , Wnt3A , Wnt1, Wnt5a, BIO, CHIR98014 , Lithium , 3F8 , derivatives thereof, and mixtures thereof. In certain embodiments, the at least one Wnt activator comprises CHIR99021 or a derivative thereof ([0157], page 9-10).
Claims 7-8 are rejected under 35 U.S.C. 103 as being unpatentable over Studer et al (Pub.. No .: US 2022/0177835 A1, Provisional application No. 62/893,674 , filed on Aug. 29, 2019) in view of Mahato et al (Movement Disorders, Vol. 35, No. 2, 2020, DOI: 10.1002/mds.27943) as evidenced by Technical Resources (Thermo Fisher Scientific - US https://www.thermofisher.com/us/en/home/technical-resources/media-formulation.251.html, Wayback machine date: 2018) as applied to claims 1-6, 9-17, 19, 21, 30-31 above, and further in view of Monje et al (WO 2020/154434 A1, International Publication Date: 30 July 2020).
The teachings of Studer et al and Mahato et al (as evidenced by Technical Resources) above are incorporated herein in their entirety.
Regarding to claim 7, Studer et al teach that suitable cell culture media include , but are not limited to , Knockout Serum Replacement (“KSR”) medium, Neurobasal medium (NB), N2 medium , B27 medium, and Essential 8/Essential 6 ( “E8/E6 ”) medium, and combinations thereof ([0182], page 13). Thus, it is a matter of choice for one of ordinary skill in the art to choose the differentiation cell culture medium comprises neurobasal medium and does not comprise N-2 and/or B-27 supplement.
Regarding to claim 7 and 8, Studer et al and Mahato et al do not teach an insulin receptor activator such as demethylasterriquinone B1 (DMAQ-B1). Monje et al cure the deficiency. Monje et al teach a method that comprises promoting or maintaining growth of a nervous system cell such as neurons ([0080], page 29). Monje et al teach TrkB agonists such as DMAQ-B1 (0075, page 28), and the provided agonist can bind an extracellular domain of TrkB, can promote TrkB phosphorylation, neurite outgrowth in vitro ([0077], page 28). Activation of TrkB can mediate neuronal differentiation and survival ([0064], Page 23).
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the rejected claims to combine the teachings of prior art to modify the method of Studer et al and Mahato et al by using insulin receptor activator such as demethylasterriquinone B1 (DMAQ-B1) as taught by Monje et al as instantly claimed, with a reasonable expectation of success. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would be motivated to do so because Monje et al provide explicit advantage of using DMAQ-B1 as TrkB agonists to activate TrkB that can promote neurite outgrowth in vitro and mediate neuronal differentiation and survival. One of ordinary skill in the art would have had a reasonable expectation of success in doing so because Monje et al provides proof of principle for using TrkB agonists to promote neurite outgrowth in vitro and mediate neuronal differentiation and survival, with detailed instruction and data.
Response to Arguments
Applicant's arguments filed 06-25-2025 have been fully considered but they are not persuasive.
1. Applicant argues that Mahato has nothing to do with 'culturing' methodology for producing functional neurons from iNPCs, in stark contrast to the present invention. The first section of Mahato's "Results" describes contacting BT13 with "immortalized cells", which were fibroblasts (see first line of the figure legend of Mahato). There is no methodology to produce functional neurons from iNPCs remotely suggested here. Indeed, the Examiner's reproduction of Figure JJ ofMahato (top of page 6 ofthe Office action) is based on an immortalized mouse fibroblast line, and has nothing to do with hiNSC differentiation.
The next three sections of Mahato's "Results" describe contacting BTJ 3 with "dopaminergic neurons". That is, cells that are already functional neurons (noting they are "dopaminergic"), and there is absolutely no hint or suggestion of culturing iNPCs with BT13. The authors of Mahato disclosed the promotion of "survival" of such (already functional) neurons (see second section of "Results"), for example providing neuroprotection (see third section of Results). Mahato has nothing to do with cell culture methodology to promote cell · differentiation - it only performed in vitro experiments on mature (already differentiated) cells to test hypotheses on the potential use of BT13 as a Parkinson's Disease (PD) drug (Remarks, page 6).
Response to Arguments:
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, Studer et al recognized the use of glial cell line-derived neurotrophic factor (GDNF) for differentiation of midbrain dopamine neuron precursors to midbrain dopamine neurons (mDAs) precursors to mDAs: the cells are contacted with DA neuron lineage specific activators and inhibitors, for example, glial cell-derived neurotrophic factor (GDNF) ([0191], page 14) (GDNF inherently bind to GDNF receptor RET and acts as an agonist for the RET receptor tyrosine kinase). Additionally, Mahato et al teach glial cell line–derived neurotrophic factor receptor rearranged during transfection agonist supports dopamine neurons in vitro and enhances dopamine release in vivo (title). Mahato et al teach GDNF receptor RET agonist, BT13, that support the survival of cultured dopamine neurons, protect cultured dopamine neurons against neurotoxin-induced cell death, activate intracellular signaling pathways both in vitro and in vivo, and regulate dopamine release in the mouse striatum as well as BT13’s distribution in the brain (Abstract). Additionally, Mahato et al also stated that “The neuroprotective and neurorestorative effects of GDNF in dopamine neurons are mediated by activation of intracellular pathways such as PI3K/AKT and MAPK, which play a role in cell survival and differentiation. In the present study, we showed that 1 μM BT13 similarly to GDNF activated ERK and AKT pathways in cultured dopamine neurons (Fig. 4 and Fig. S2). It is important to note that 1 μM BT13 also promoted the survival of naive dopamine neurons (Fig. 2) and protected them from toxin-induced death (Fig. 3)” (see page 253, left column, 3rd para). Moreover, Since Studer et al teach method to sustain expression of EN1 to exert neuroprotective and physiological function in adult midbrain DA neurons ([0187], page 13) and Mahato et al teach GDNF receptor RET agonist, BT13, that support the survival of cultured dopamine neurons, protect cultured dopamine neurons against neurotoxin-induced cell death (Abstract), a person of ordinary skill in the art before the effective filing date of the rejected claims would be motivated to combine and modify the method of generating
midbrain dopamine neurons as taught by Studer et al by using DA neuron lineage specific activators such as GDNF receptor RET agonist, BT13, as taught by Mahato et al to protect cultured dopamine neurons against neurotoxin-induced cell death as instantly claimed, with a reasonable expectation of success.
2. Applicant argues that “all of Mahato's data are based on mouse cells, whereas the present invention applies the RET agonist to human cells for the first time ….such that extrapolating the precise effects of one specific compound from one species to the other is not predictable, especially for a complex
phenotypic change such as cell differentiation.” (Remarks, page 6-7).
Response to Arguments:
It is noted that the entire study of Mahato et al is to develop a novel treatment for PD Parkinson’s disease (PD) for PD human patients (Page 246, right column, 1st para). Also, Mahato et al teach a neurotrophic effect of GDNF in the treated patients and in the recent phase II trial, a post hoc analysis found 9 (43%) patients only in the GDNF-treated group with a large clinically important motor improvement in the OFF state (Page 246, left column, 2nd para.). Thus, it is expected that RET agonist such as GDNF and BT13 to perform in similar fashion in human.
Applicant's arguments amount to nothing more than conjecture mere allegations of patentability. As per MPEP 716.01(c) (II), arguments presented by the applicant cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965) and In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984). Examples of statements which are not evidence and which must be supported by an appropriate affidavit or declaration include statements regarding unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the inventor or at least one joint inventor.
3. Applicant argues that the Applicant has, for the first time, demonstrated the ability to use a GDNF receptor RET "agonist'' to promote maturation of iNPCs into functional neurons, indeed while providing data that this even provides the opportunity to omit not only the traditional GDNF protein molecule, but optionally also the BDNF and TGFB proteins (a significantly advantageous data point toward GMP manufacturing)~ see Figure l of the application as filed. This was totally unexpected - many research labs dedicate significant resources to investigating in vitro differentiation conditions given the complexity of such process, and the present application provides a significant contribution to the art (remarks, page 7).
Response to Arguments:
As per MPEP § 716.02, any 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). In this case, there is no evidence of record that using a GDNF receptor RET "agonist'' to promote maturation of iNPCs into functional neurons would leads to unexpected results as compared to the teachings of prior arts. Specifically, Studer et al recognized the use of glial cell line-derived neurotrophic factor (GDNF) for differentiation of midbrain dopamine neuron precursors to midbrain dopamine neurons (mDAs) precursors to mDAs: the cells are contacted with DA neuron lineage specific activators and inhibitors, for example, glial cell-derived neurotrophic factor (GDNF) ([0191], page 14) (GDNF inherently acts as an agonist for the RET receptor tyrosine kinase). Additionally, Mahato et al teach GDNF receptor RET agonist, BT13, that support the survival of cultured dopamine neurons, protect cultured dopamine neurons against neurotoxin-induced cell death, activate intracellular signaling pathways both in vitro and in vivo, and regulate dopamine release in the mouse striatum as well as BT13’s distribution in the brain (Abstract). Mahato et al also recognized the “The neuroprotective and neurorestorative effects of GDNF in dopamine neurons are mediated by activation of intracellular pathways such as PI3K/AKT and MAPK, which play a role in cell survival and differentiation” and Mahato et al showed that BT13 similarly to GDNF activated ERK and AKT pathways in cultured dopamine neurons (Fig. 4 and Fig. S2) that promoted the survival of naive dopamine neurons (Fig. 2) and protected them from toxin-induced death (Fig. 3) (see page 253, left column, 3rd para). Applicant has not provided or pointed out what is unexpected/superior results over prior arts. Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
4. Applicant argues that there would be an element of impermissible hindsight if the "GDNF protein" component is specifically homed in on to allege that it would have been adapted based on the cited documents (remarks, Page 7-8).
Response to Arguments:
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
5. Applicant argues that there is nothing in Mahato that would have provided the skilled person with motivation to use some sort of "agonist'' as disclosed therein to help promote the production of neurons from iNPCs. Mahato only looked at effects that the disclosed agonist might have on 'already' mature/functional neurons, for the sole reason of positioning the agonist itself as a candidate drug. These documents were not even remotely concerned with in vitro "differentiation" methodology, and cannot be alleged to have motivated the presently claimed solution. The process of cell differentiation is complex, and there was no reasonable expectation that the effects of the agonist (in the cited documents) on already functional neurons would have any effect (let alone a positive one) in a differentiation process. At the very least, a research program would need to have been conducted to investigate the latter. Applicant would like to take the opportunity to contend that, in the technical field of pluripotent cell differentiation studies, a skilled person in this art can be expected to dedicate significant attention to actually replicating prior established differentiation protocols as precisely as possible, indeed down to the brand/manufacturer of a culture component, going so far as to keep the production lot consistent, if possible, to derisk an experiment because pluripotent cells are notably sensitive to changes in culture environment. Therefore, it would take a very unconventional and risky (therefore also original and inventive) approach to supplement or replace a previously established component. There was nothing in the prior art that would have sufficiently motivated the skilled person to add a small molecule GDNF receptor RET "agonist'', because they would have stuck to something they could have more cautiously used, e.g. the previously used "GDNF protein" component (remarks, Page 8).
Response to Arguments:
As mentioned above, Studer et al recognized the use of glial cell line-derived neurotrophic factor (GDNF) for differentiation of midbrain dopamine neuron precursors to midbrain dopamine neurons (mDAs) precursors to mDAs: the cells are contacted with DA neuron lineage specific activators and inhibitors, for example, glial cell-derived neurotrophic factor (GDNF) ([0191], page 14) (GDNF inherently acts as an agonist for the RET receptor tyrosine kinase). Additionally, Mahato et al also recognized the “The neuroprotective and neurorestorative effects of GDNF in dopamine neurons are mediated by activation of intracellular pathways such as PI3K/AKT and MAPK, which play a role in cell survival and differentiation” and Mahato et al showed that BT13 similarly to GDNF activated ERK and AKT pathways in cultured dopamine neurons (Fig. 4 and Fig. S2) that promoted the survival of naive dopamine neurons (Fig. 2) and protected them from toxin-induced death (Fig. 3) (see page 253, left column, 3rd para). Thus, a person of ordinary skill in the art before the effective filing date of the rejected claims would be motivated to combine and modify the method of generating midbrain dopamine neurons as taught by Studer et al by using DA neuron lineage specific activators such as GDNF receptor RET agonist, BT13, as taught by Mahato et al to protect cultured dopamine neurons against neurotoxin-induced cell death as instantly claimed, with a reasonable expectation of success.
Applicant's arguments amount to nothing more than conjecture mere allegations of patentability. As per MPEP 716.01(c) (II), arguments presented by the applicant cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965) and In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984). Examples of statements which are not evidence and which must be supported by an appropriate affidavit or declaration include statements regarding unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the inventor or at least one joint inventor.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KHOA NHAT TRAN whose telephone number is (571)270-0201. The examiner can normally be reached M-F (9-5).
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/KHOA NHAT TRAN/Examiner, Art Unit 1632
/PETER PARAS JR/Supervisory Patent Examiner, Art Unit 1632