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 .
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant’s claim for priority to a provisional application 63/050,736 is acknowledged. The effective filing date for claims 1-16 is July 10, 2020.
Claim Status
In Applicants response filed May 5, 2025, the Applicant has amended claim 1, 2, 9, 12, and 15.
Applicant’s election without traverse of claims 1-16 in the reply filed on July 05, 2023, is acknowledged. Claims 17-26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on July 5, 2023.
Claims 1-16 are currently under examination.
Withdrawn Objections & Rejections
Rejections and/or objections not reiterated from the previous office action are hereby withdrawn due to amendment. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Affidavit or Declaration under 37 CFR 1.130(a)
The affidavit under 37 CFR 1.132 filed by Dr. Asimina Gkouti on May 5, 2025 is insufficient to overcome the obviousness rejection of claims 1-16 based on Gouti et al., (Developmental cell 41.3: 243-261, published 2017, cited IDS 7/9/2021, previously Briscoe, here in after as “Gouti”), Ichida, et al., (Cell Stem Cell 26.2: 131-133, published Feb. 2020; cited IDS 11/17/2021), Gouti, et al. (PLoS biology 12.8: e1001937, published 2014; cited IDS 7/9/2021), Vernardis, et al., (Sci Rep 7, 42138, published 2017), Camp et al. (Proceedings of the National Academy of Sciences 112.51: 15672-15677, published 2015), and Bolognin et al., (US2018/0298330 A1, published 2017; cited IDS 11/17/21) as set forth in the last Office action because Gouti’s affidavit is fails to establish that the claimed subject matter in the disclosure was made solely by the inventor. The affidavit under 37 CFR 1.130(a) recites “I, Asimina Gkouti invented the idea of using the organoid in disease modelling, any subject matter in the Ichida reference was obtained from my manuscript” (see page 2). Further, Asimina Gkouti’s declaration is ineffective because it lacks a reasonable explanation of the Ichida and Ko’s role in the non-patent literature.
MPEP 717.01 states – “In evaluating whether a declaration under 37 CFR 1.130(b) is effective to disqualify a disclosure on which the rejection is based, Office personnel will consider the following criteria”:
(B) Whether the affidavit or declaration shows sufficient facts, in weight and character, to establish that the subject matter disclosed had, before such disclosure was made or before such subject matter was effectively filed, been publicly disclosed by: (1) the inventor or a joint inventor; or (2) another who obtained the subject matter disclosed directly or indirectly from the inventor or a joint inventor.
MPEP 2155.01 states “Where the authorship of the prior art disclosure includes the inventor or a joint inventor named in the application, an unequivocal statement from the inventor or a joint inventor that the inventor or joint inventor (or some combination of named inventors) invented the subject matter of the disclosure, accompanied by a reasonable explanation of the presence of additional authors, may be acceptable in the absence of evidence to the contrary. See In re DeBaun, 687 F.2d 459, 463, 214 USPQ 933, 936 (CCPA 1982).”
When any claim of an application or a patent under reexamination is rejected, the applicant or patent owner may submit an appropriate affidavit or declaration to except a disclosure as prior art by establishing that the disclosure was made by the inventor or a joint inventor, or the subject matter disclosed was obtained directly or indirectly from the inventor or a joint inventor. However, an affidavit or declaration under 37 CFR 1.130(a) that is only a naked assertion of inventorship and that fails to provide any context, explanation or evidence to support that assertion is insufficient. See EmeraChem Holdings, LLC v. Volkswagen Grp. of Am., Inc., 859 F.3d 1341, 123 USPQ2d 1146 (Fed. Cir. 2017). See also Ex parte Kroger, 219 USPQ 370 (Bd. App. 1982) (affirming rejection notwithstanding declarations by the alleged actual inventors as to their inventorship in view of a nonapplicant author submitting a letter declaring the nonapplicant author's inventorship). This is similar to the process for disqualifying a publication as not being by "others" discussed in MPEP § 2132.01, except that AIA 35 U.S.C. 102(b)(1)(A) requires only that the disclosure be by the inventor or a joint inventor.
Accordingly, the affidavit or declaration to the except of disclosure as prior art needs to establish that the disclosure was made by the inventor (i.e. the sole inventor of the claimed invention) by showing sufficient facts, in weight and character, to establish that the subject matter disclosed had, before such disclosure was made or before such subject matter was effectively filed (see Example 4, MPEP 2155.01). The MPEP states that the attorney submits either a new declaration under 37 CFR 1.130(a) which states that Gkouti invented the claimed subject matter or an inventor's oath or declaration under 37 CFR 1.63 signed by Gkouti.
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.
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.
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 1-16 are rejected under 35 U.S.C. 103 as being unpatentable over Gouti et al., (Developmental cell 41.3: 243-261, published 2017, cited IDS 7/9/2021; hereinafter as “Gouti”, prior art of record), Bolognin et al., (US2018/0298330 A1, published 2017; cited IDS 11/17/21, prior art of record), and Gouti, et al. (PLoS biology 12.8: e1001937, published 2014; cited IDS 7/9/2021, prior art of record, hereinafter as “Gouti 2014”), Vernardis, et al., (Sci Rep 7, 42138, published 2017, prior art of record), Sareen et al., (WO2018/170180A1, published 2018, cited IDS 11/17/2021), and as evidence by Ichida, et al., (Cell Stem Cell 26.2: 131-133, published Feb. 2020; cited IDS 11/17/2021, prior art of record) and Camp et al. (Proceedings of the National Academy of Sciences 112.51: 15672-15677, published 2015, prior art of record).
This is a new rejection necessitated by amendment to the claims. However, since it is
substantially similar to a rejection set forth in the non-final Official action mailed 04 February
2025, any aspect of applicant's response considered relevant to the rejection as newly set forth is responded to following the statement of rejection.
Regarding claim 1, Gouti discloses a method for generating three-dimensional in vitro neuromesodermal progenitor cells (NMPs)(see e.g. Supplemental section page e3, ESC culture and Differentiation).
Regarding claim 1a, Gouti teaches providing a first cell culture comprising neuromesodermal progenitor cells (NMP) and cultivating the neuromesodermal progenitor cells in a first differentiation medium corresponding to the claim limitation of i) a non-supplemented serum-free cell culture medium. Gouti teaches ‘N2B27’ medium (NB) which is the same non-supplemented serum-free cell culture medium as recited in the specification (Specification see e.g. page 5). Further, Gouti teaches the serum-free culture medium is supplemented with an activator of a growth factor signaling pathway (e.g. basic fibroblast growth factor (bFGF))(see e.g. Supp. Sec. page e3, Fig. 2-4). Further, the bFGF reads on the claimed activator of a growth factor signaling pathway (see e.g. specification page 6).
Regarding claim 1a, Gouti discloses cells may be dissociated into a single cell suspension using accutase (see e.g. page e3). Further, the prior art of Bolognin discloses generating organoids in a single cell suspension (see e.g. para. 18, 38, 107, page 20, 45 and sec. 2.3).
Accordingly, it would have been obvious for a person of ordinary skill in the art to modify the three-dimensional neuromuscular organoid methods as taught by Gouti with a single cell suspension as taught by Bolognin and Gouti because Gouti discloses investigate the dynamical changes of the transcriptional profile as cells differentiate (see e.g. supp. page e4). Further, Gouti cites Camp for analyzing the small clumps of cells through single-cell genomics (SCG). Further, the prior art of Camp discloses that SCG offer new opportunities (i.e. characterize engineered cells at the level of chromatin organization and epigenetic marks) to test existing differentiation protocols and their limitations (see e.g. page 661, 664). Additionally, Bolognin discloses generating organoids from a single cell suspension (see e.g. page 2, 15). Therefore, a person of ordinary skill in the art would have a reasonable expectation of success of generating a three-dimensional neuromuscular organoid as taught by Gouti with a single-cell suspension as discloses by Gouti and Bolognin because both utilize single cell suspensions. An artisan of ordinary skill in the art of tissue engineering has good reason to pursue the known options within his or her technical grasp (KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (US 2007).
Regarding claim 1b, Gouti teaches replacing the first differentiation medium by a second differentiation medium within 3 days after cultivation start (see e.g. Supp. sec. page e3, ESC culture and Differentiation). Further, Gouti teaches i) the second differentiation medium is chosen from the group consisting of i) a non-supplemented serum-free cell culture medium (i.e. N2B27 medium).
Regarding claim 1c, Gouti teaches that the NMPs were passaged every 3 days corresponding to the claim limitation of replacing the second differentiation medium by a non-supplemented serum-free cell culture medium within 1 to 3 days after replacing the first differentiation medium by the second differentiation medium (see e.g. Supp. Sec. page e3, ESC culture and Differentiation, fig. 2-4).
Regarding claim 1d, Gouti discloses that the cells were “dissociated into small cellular clumps mechanically using a plastic pipette tip” (see e.g. Supp. Sec. page e3, ESC culture and Differentiation, fig. 2-4) (i.e. neuromuscular organoids). Further, Gouti cites Camp for analyzing the small clumps of cells (i.e. organoids). It would have been obvious for a person of ordinary skill in the art to associate the small cellular clumps as neuromuscular organoids because Camp teaches analyzing gene expression for cerebral organoids (see e.g. abstract of Camp).
Gouti does not explicitly state the term “organoid”.
However, the prior art Ichida 2020, provides evidence that neural/mesodermal organoids (i.e. neuromuscular organoids) were formed after 5 days of culture following the same protocol as Gouti protocol (i.e. both of the prior arts reference Gouti 2014)(see e.g. page 131, Fig. 1).
Accordingly, it would have been obvious for a person of ordinary skill in the art at the time of the invention to obtain three-dimensional neuromuscular organoid from the non-supplemented serum-free cell culture medium as taught by Gouti with a reasonable expectation of success. A person of ordinary skill in the art would have been motivated to generate a three-dimensional neuromuscular organoid from neuromesodermal progenitor cells (NMPs) as taught by Gouti because Gouti teaches that in vitro and in vivo NMPs are molecularly and functionally similar (see e.g. page 244). Furthermore, Gouti cites Gouti 2014 for their protocol of generating three-dimensional organoids from NMP cells (see e.g. page 246), and Ichida cites Gouti 2014 for teaching the basis of the three-dimensional organoids from NMP cells strategy (see e.g. page 131, Figure 1). Hence, a person of ordinary skill in the art would have interpreted the cells obtained by Gouti method as neuromuscular organoids. Ex parte Marhold, 231 USPQ 904, 905 (Bd. Pat. App. & Int. 1986) relying on In re Sussman, 141 F.2d 267, 269-70, 60 USPQ 538, 540-41 (CCPA 1944) provides "that since the steps are the same, the results must inherently be the same unless they are due to conditions not recited in the claims." Therefore, Gouti (2017) teaches that generating three-dimensional organoids from NMP cells would have been done with a reasonable expectation of success.
Regarding claim 2, Gouti teaches wherein the non-supplemented serum-free cell culture medium is Dulbecco's Modified Eagle Medium comprising Ham's F12 medium and neurobasal medium (NB)(see e.g. Supp. Sec. page e3, Fig. 2-4).
Regarding claim 3, as discussed above, Gouti teaches wherein the activator of a growth factor signaling pathway is the fibroblast growth factor (i.e. bFGF) signaling pathway (Supplemental see page e3, fig. 2-4) as discussed above.
Regarding claim 4-5, as discussed above, Gouti teaches a second differentiation medium is a serum free cell culture medium (Supplemental see page e3). Further, Gouti teaches the serum-free culture medium is supplemented with an activator of a growth factor signaling pathway (e.g. basic fibroblast growth factor (bFGF))(see e.g. Supp. Sec. page e3, Fig. 2-4).
Gouti is silent regarding supplementing with a ROCK inhibitor, an insulin-like growth factor and hepatocyte growth factor.
However, the prior art of Gouti 2014 teaches supplementing the N2B27 medium with Y-27632 (i.e. ROCK inhibitor) and Sareen discloses supplementing a maturation media with hepatocyte growth factor (HGF), and insulin growth factor (IGF)(see e.g. page 29-32).
Accordingly, it would have been obvious for a person of ordinary skill in the art at the time of the invention to modify the method of Gouti to obtain a three-dimensional neuromuscular organoid from the non-supplemented serum-free cell culture medium by supplementing with a ROCK inhibitor, an insulin-like growth factor and hepatocyte growth factor as taught by Gouti 2014 and Sareen with a reasonable expectation of success. A person of ordinary skill in the art would have done so because it was known in the prior art that supplementing media with hepatocyte growth factor (HGF), and insulin growth factor (IGF) factors promotes expansion. Additionally, Gouti references Gouti’s (i.e. Gouti 2014) protocol for generating NMPs from pluripotent stem cells. Thus, providing a reasonable expectation of success. Further, the use of growth factors for supplementing medium is extremely well known in the field of cell culture art. An artisan of ordinary skill in the art of culturing skeletal muscle cells has good reason to pursue the known options within his or her technical grasp (KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (US 2007).
Regarding claim 6, as discussed above, Gouti teaches that the non-supplemented serum-free cell culture medium after step c) that was changed every other day (i.e. every 2 days)(Supplemental see page e3). Further, Gouti teaches that the NMP cells could be maintained for up to 10 days (see e.g. page 253).
Gouti is silent regarding wherein the time period exceeds 10 days after the start of cultivation.
However, Bolognin discloses culturing in a differentiation medium for at least 10 days or more (see e.g. page 7).
Further, the following is noted from the MPEP: MPEP 2144.05: “In the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990).” MPEP 2144.05(I) teaches “a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close.” Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985).”
Accordingly, it would have been obvious for a person of ordinary skill in the art at the time of the invention to employ the method of obtaining a three-dimensional neuromuscular organoid from the non-supplemented serum-free cell culture medium as taught by Gouti with the culturing time period as discloses by Ichida and Bolognin with a reasonable expectation of success. A person of ordinary skill in the art would have been motivated to do so because Ichida discloses that “over the next 50–100 days, the organoids reached 5–6 mm in diameter and displayed an elongated morphology with neural tissue on one end and muscle cells on the other” (see page 131, col. 3). Further, Ichida discloses that the “segregation of neural and muscle compartments was maintained at day 50 when anatomical and functional NMJs became apparent” (see page 131, col. 3). Thus, providing a reasonable expectation of success.
Gouti is silent regarding wherein the method is carried out under agitation.
As discussed above, Bolognin teaches a method of generating brain organoids (see e.g. abstract).
Regarding claim 7, Bolognin teaches a method of generating brain organoids by contacting them with differentiation medium under agitating conditions (see e.g. abstract).
Accordingly, it would have been obvious for a person of ordinary skill in the art at the time of the invention to modify the method of Gouti to obtain a three-dimensional neuromuscular organoid from the non-supplemented serum-free cell culture medium with agitation conditions as taught by Bolognin with a reasonable expectation of success. A person of ordinary skill in the art would have been motivated to do so because Bolognin teaches that under agitating conditions the stem cells that were embedded in three-dimensional cell culture grew further and quickly (see e.g. para. 9). Additionally, both Gouti and Bolognin discloses methods for obtaining a neural organoid in a three-dimensional cell culture from stem cells (e.g. embryonic stem cells). Thus, providing a reasonable expectation of success.
Regarding claim 8, Gouti teaches wherein the first cell culture comprises 30 % to 90% neuromesodermal progenitor cells co-expressing BRACHYURY(T/BRA or Bra)/SOX2 and 10 % to 70 % neuromesodermal progenitor cells co-expressing TBX6 (see e.g. page 244 and Fig. 3-5)
Regarding claims 9-12, Gouti teaches wherein the neuromesodermal progenitor cells are obtained by providing a second cell culture comprising pluripotent stem cells and cultivating the pluripotent stem cells in a first cultivation medium comprising a serum-free cell culture medium supplemented with an activator of β-catenin signaling pathway (i.e. CHIR99021 is 6-[[2-[[4-(2,4-Dichlorophenyl)-5-(5-methyl-1 H-imidazol-2-yl)-2-pyrimidinyl] amino]ethyl]amino ]-3-pyridinecarbonitrile)(see e.g. Supp. Sec. page e3, Fig. 6A). Further, CHIR99021 is a known activator of β-catenin signaling pathway is an inhibitor of glycogen synthase kinase 3 activity (Specification, see e.g. page 8-9).
Regarding claims 13-14, as discussed above, Gouti teaches wherein the activator of a growth factor signaling pathway is chosen from the group consisting of an activator of the fibroblast growth factor signaling pathway (see e.g. Supp. Sec. page e3, Fig. 2-4).
Regarding claim 15, as discussed above, Gouti teaches wherein the first cultivation medium is changed against (i.e. replaced with) a second cultivation medium 1 to 3 days after cultivation start, wherein the second cultivation medium comprises a serum-free cell culture medium supplemented with at least one of an activator of β-catenin signaling pathway and an activator of a growth factor signaling pathway(i.e. bFGF) (page e4) (see e.g. Supp. Sec. page e3, Fig. 2-4).
Regarding claim 16, as discussed above, Gouti teaches that the non-supplemented serum-free cell culture medium (see e.g. Supp. Sec. page e3, Fig. 2-4).
Gouti is silent regarding the first cultivation medium contains a ROCK inhibitor, but the second cultivation medium does not contain a ROCK inhibitor.
However, the prior art of Gouti 2014 teaches the first cultivation medium contains a ROCK inhibitor (i.e. Y-27632) and the second cultivation medium does not contain a ROCK inhibitor (see e.g. page 12).
Accordingly, it would have been obvious for a person of ordinary skill in the art at the time of the invention to modify the method of Gouti to obtain a three-dimensional neuromuscular organoid from the non-supplemented serum-free cell culture medium by supplementing with the first cultivation medium contains a ROCK inhibitor, but the second cultivation medium does not contain a ROCK inhibitor as taught by Gouti with a reasonable expectation of success. A person of ordinary skill in the art would have been motivated to do so because the prior art of Vernardis teaches that “robust differentiation protocols necessitate single cell cultures that are achieved by use of ROCK (Rho kinase) inhibitors” (see e.g. abstract). Further, Vernardis teaches that it was known in the prior art for “ROCK inhibition to enable maintenance of stem cell phenotype” (see e.g. abstract). Therefore, it would have been obvious for a person of ordinary skill in the art to remove the ROCK inhibitor during the second cultivation medium. Furthermore, Gouti references Gouti’s (i.e. Gouti 2014) protocol for generating NMPs from pluripotent stem cells. Thus, providing a reasonable expectation of success.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Response to Traversal:
Applicant's arguments filed May 5, 2025, are acknowledged, have been fully considered, and deemed persuasive.
Applicant asserts that the declaration under 37 CFR 1.130(a) filed by Dr. Asimina Gkouti on May 5, 2025, disqualifies Ichida, et al., (Cell Stem Cell 26.2: 131-133, published Feb. 2020; cited IDS 11/17/2021) as prior art (Remarks, page 9).
As stated above, the declaration under 37 CFR 1.132 filed by Dr. Asimina Gkouti on May 5, 207/29/2024 is insufficient to overcome the obviousness rejection of claims 1-16 based on Gouti et al., (Developmental cell 41.3: 243-261, published 2017, cited IDS 7/9/2021; previously as “Briscoe” hereinafter as “Gouti”), Ichida, et al., (Cell Stem Cell 26.2: 131-133, published Feb. 2020; cited IDS 11/17/2021), Gouti, et al. (PLoS biology 12.8: e1001937, published 2014; cited IDS 7/9/2021, hereinafter as “Gouti 2014”), Vernardis, et al., (Sci Rep 7, 42138, published 2017), Camp et al. (Proceedings of the National Academy of Sciences 112.51: 15672-15677, published 2015), and Bolognin et al., (US2018/0298330 A1, published 2017; cited IDS 11/17/21) as set forth in the last Office action because Gouti’s affidavit is fails to establish that the claimed subject matter in the disclosure was made solely by the inventor.
Applicant argues that Gouti (i.e. Briscoe) “discloses a method to generate neuromesodermal progenitor cells from stem cells (see paragraph "ESC Culture and Differentiation" on page e3 of Gouti) as the outcome of the described method. Therefore, in the method described by Gouti, the neuromesodermal progenitor cells are the product, while in the presently claimed subject matter the neuromesodermal progenitor cells are a necessary source” (Remarks, page 10).
Applicant arguments are acknowledged, have been fully considered, and have been deemed unpersuasive. In response to applicant's argument that Gouti discloses the outcome while the claims are directed to the source, 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, as discussed above, Gouti cites Gouti 2014 for their protocol of generating three-dimensional organoids from NMP cells (see e.g. page 246), and Ichida cites Gouti (2014) for teaching the basis of the three-dimensional neuromuscular organoids from NMP cells (see e.g. page 131, Figure 1). Hence, a person of ordinary skill in the art would have interpreted the cells obtained by Gouti’s method as neuromuscular organoids as taught by Gouti 2014. Ex parte Marhold, 231 USPQ 904, 905 (Bd. Pat. App. & Int. 1986) relying on In re Sussman, 141 F.2d 267, 269-70, 60 USPQ 538, 540-41 (CCPA 1944) provides "that since the steps are the same, the results must inherently be the same unless they are due to conditions not recited in the claims." Therefore, the teachings of Gouti and Gouti 2014 generating three-dimensional organoids from NMP cells would have been done with a reasonable expectation of success. Furthermore, 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).
The Examiner also notes that the claim recites “comprising the following steps” which allows for additional steps that are not recited between the recited steps (i.e. comprising is open-ended). See MPEP 2111.03.
Applicant argues that “Gouti (i.e. Briscoe) leads to neuromesodermal progenitor cells dissociated into "cellular clumps" (page e3 of Gouti), while the amended claim 1 requires neuromesodermal progenitor cells in single cell suspension”. Further, Applicant argues that there is “no hint or suggestion in Gouti (i.e. Briscoe) to use these generated "cellular clumps"”(Remarks, page 10). Applicant further argues that Gouti (i.e. Briscoe) cites Camp et al. in the context of its usage of “minimal spanning trees (MST)," and the enclosed publication (Trapnell et al 2014) developed the software, and the analysis does not require data from an organoid (Remarks, page 10-11).
In response to applicants’ arguments, Gouti actually discloses the ability of the cells being dissociated into a single cell suspension using accutase for FACs analysis (see e.g. page e3). Additionally, the prior art of Bolognin discloses generating organoids from a single cell suspension (see e.g. para. 18, 38, 107, page 20, 45 and sec. 2.3). Furthermore, the specification discloses that the “in vitro generation of NMPs from Human Pluripotent Stem Cells were grown for at least three passages and after they reached 70% confluency they were dissociated into single cells using accutase” (Spec. para. 156). Therefore, since both the methods of Gouti and Bolognin, and the specification disclose using accutase for generating single cell suspension, it would have been possible to modify the method to obtain a single cell suspension with a reasonable expectation of success because the method was known in the prior art.
In response to applicant argument that Trapnell et al 2014 provides evidence that developed the software does not require organoids, the Examiner notes that the reference of Trapnell is not enclosed, however the argument of Camp et al. and Trapnell is not persuasive because Camp et al. evidence that a single cell suspension would be beneficial reciting that “comparison of in vivo and in vitro cortical single-cell transcriptomes illuminates the genetic features underlying human cortical development that can be studied in organoid cultures” (see e.g. abstract). Furthermore, Gouti discloses analyzing the “small cellular clumps” through FACs and a single-cell state graph to investigate the changes of transcriptional profiles of the structures which can revel “the differentiation trajectories and intermediate states that underlie the clusters of similar cells (i.e. the ‘‘clustered’’ populations)”(see e.g. page e3-e4). Additionally, the prior art of Bolognin discloses generating organoids from a single cell suspension (see e.g. para. 18, 38, 107, page 20, 45 and sec. 2.3), as discussed above. Moreover, an artisan of ordinary skill in the art of tissue engineering has good reason to pursue the known options within his or her technical grasp (KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (US 2007).
The MPEP 2123 (I) states that patents are relevant as prior art for all they contain, and that a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. In instant case, the TCRs and CARs to be included in the T cell taught by Valdes are typical agents found in the cell therapy art (see Background, [0004] of Valdes) and appear both in the specification and in the claims. Applicant is reminded that preferred embodiments are not the only teaching of a reference. “The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain.” In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) (quoting In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)). A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989).
Applicants are reminded that the test for obviousness is not whether the features of a secondary reference maybe bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413,208 USPQ 871 (CCPA 1981).
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 JOSEPHINE GONZALES whose telephone number is (571)272-1794. The examiner can normally be reached M-Th: 9AM - 5:00PM (EST).
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JOSEPHINE GONZALES
Examiner
Art Unit 1631
/JOSEPHINE GONZALES/ Examiner, Art Unit 1631
/JAMES D SCHULTZ/ Supervisory Patent Examiner, Art Unit 1631
Prosecution Insights