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 .
Election/Restrictions
Applicant’s election of Group I (Claims 1-4, 7-14, and 17-18; drawn to a method comprising contracting a population of cells comprising pancreatic progenitor cells or precursors thereof with a composition comprising an inhibitor IL-4/JAK3 signaling pathway) in the reply filed on June 23, 2025, is acknowledged.
Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 20-24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention (Groups II-VI), there being no allowable generic or linking claim. Election was made without traverse in the reply filed on May 7, 2024.
Applicant further elected the following species:
a. 10 μM concentration for the IL-4/JAK3 inhibitor
DETAILED ACTION
The amended claims filed on November 10, 2025, have been acknowledged. Claims 5-6, 15-16, and 19-24 were cancelled. Claims 1-2, 4, 7-13, and 17-18 were amended. Claims 1-4, 7-14, and 17-18 are pending and examined on the merits.
Priority
The applicant claims domestic priority from U.S. provisional application No. 62/886,049, filed on August 13, 2019. 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. Claims 1-4, 7-14, and 17-18 receive domestic benefit from U.S. provisional application No. 62/886,049, filed on August 13, 2019.
Withdrawn Claim Rejections - 35 USC § 112
The prior rejection of claims 1-3, 5, 7-18 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112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn in light of Applicant’s amendments to claim 1 to specifically identify the IL-4/JAK3 inhibitors.
Claims 1-6, 8, and 10-15 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112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn in light of Applicant’s amendments to claim 1 to state that the method comprises differentiating said pancreatic progenitor cells into NKX6.1 positive and ISL1 negative cells instead of enterochromaffin cells.
Claim Rejections - 35 USC § 112
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 1-4, 7-14, and 17-18 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. This is a new rejection in light of Applicant’s amendments to claim 1.
Claim 1 recites the following claim language, “differentiating said pancreatic progenitor cells into NKX6.1 positive and ISL1 negative” Based on the data provided by the Applicant, it is not clear that they have differentiated pancreatic progenitor cells into NKX6.1 positive and ISL1 negative cells.
Under the written description guidelines (see MPEP 2163) the Examiner is directed to determine whether one skilled in the art would recognize that the Applicant was in possession of the claimed invention as a whole at the time of filing. The following considerations are critical to this determination.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. An original claim may lack written description support when (1) the claim defines the invention in functional language specifying a desired result but the disclosure fails to sufficiently identify how the function is performed or the result is achieved or (2) a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349-50 (Fed. Cir. 2010) (en banc). The written description requirement is not necessarily met when the claim language appears in ipsis verbis in the specification. "Even if a claim is supported by the specification, the language of the specification, to the extent possible, must describe the claimed invention so that one skilled in the art can recognize what is claimed. The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement." Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002).
Accordingly, to satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.
Actual Reduction to Practice
In regard to claim 1 encompassing differentiating pancreatic progenitor cells into NKX6.1 positive and ISL1 negative cells, the specification provides Example 1 and Figure 1 as evidence that they produced NKX6.1 positive and ISL1 negative cells by culturing stage 5 pancreatic progenitor 2 cells with an exemplary JAK3 inhibitor in stage 5 culture media. They cite to Figure 1 which purports to show an increase in the number of Nkx.1+/ISL1- cells. However, although there appears to be an increase in the number of cells in quadrant 3 (32.8% to 45.5%), these quadrant 3 cells still express high levels of ISL1 (roughly 103-104 expression levels). As there is no further characterization of these quadrant 3 cells that are purportedly Nkx.1+/ISL1- cells, it is not clear from Figure 1 alone that these cells are Nkx.1+/ISL1- cells as claimed.
Veres et al. (Nature 569: 368-373. 2019; referenced in IDS) evidences that ISL1 is considered a branch gene associated with SC-β cells and drops in expression in cells that differentiate into enterochromaffin cells instead of SC-β cells (Figure 5). Furthermore, Veres evidences that enterochromaffin and SC-β cells are NKX6.1+ ISL1 expression in SC-β cells is in the 103-104 range (Figure 1 and Extended Data Figure 5)
Similarly, Gehart et al. (Cell 176: 1158–1173. 2019) evidences that Isl1 expression was associated with non-enterochromaffin trajectory and that enterochromaffin cells have low levels of ISL1 expression (page 1166, column 1, paragraph 1-column 2, paragraph 3 and Figures 5 and 6).
As such, based on the evidence from Veres and Gehart that ISL1 expression is associated with differentiating a similar progenitor into a non-enterochromaffin cell that shows expression levels of ISL1 that are comparable to what is found in Figure 1 of the instant specification, it is not clear that the cells of quadrant 3 of the instant application represent ISL1- cells due to their high expression of ISL1.
Accordingly, Applicant did not demonstrate a reduction to practice differentiating pancreatic progenitor cells into NKX6.1 positive and ISL1 negative cells, nor did Applicant adequately set forth in terms of distinguishing identifying characteristics as evidenced by other descriptions of the invention that are sufficiently detailed to show that Applicant was in possession of the claimed method of differentiating pancreatic progenitor cells or precursors thereof into enterochromaffin cells.
Disclosure of structure and relevant identifying characteristics
The breadth of the claims encompass differentiating pancreatic progenitor cells into NKX6.1 positive and ISL1 negative cells by contacting the cells with an inhibitor of IL-4/JAK3 signaling pathway as identified in claim 1, yet the present specification provides only guidance on contacting pancreatic progenitor 2 cells with an unidentified JAK3 inhibitor to increase the number of cells NKX6.1+ and cells with reduced ISL1 expression (purportedly ISL1- cells). The Applicant has identified the cells of quadrant 3 of Figure 1 to be ISL1- cells based on their reduced expression of ISL1 compared to quadrant 2 cells (top right section). However, as stated supra, enterochromaffin cells are known to not express ISL1 as this leads to differentiation into SC-β cells instead of enterochromaffin cells and the cells of quadrant 3 still express high levels of ISL1 that are comparable to the levels found in SC-β, As such, this suggests the cells of quadrant 3 are still ISL1+. Therefore, the skilled artisan would not know what rational approach to take for the methods of differentiating pancreatic progenitor cells into NKX6.1 positive and ISL1 negative cells using an inhibitor of IL-4/JAK3 signaling pathway and whether the identified method of contacting pancreatic progenitor 2 cells with a JAK3 inhibitor is sufficient to produce NKX6.1 positive and ISL1 negative cells as claimed. As such, it is incumbent on the applicant to provide this nexus between structure and function, in order to be given credit for possession of the claimed methods of differentiating any pancreatic progenitor cells or any precursor of pancreatic progenitor cells into NKX6.1 positive and ISL1 negative cells using an inhibitor of IL-4/JAK3 signaling pathway.
An applicant may show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics. Enzo Biochem, 323 F.3d at 964, 63 USPQ2d at 1613.
STATE OF THE ART & QUANTITY OF EXPERIMENTATION
Although methods of making NKX6.1 positive and ISL1 negative cells in vitro are known as identified by Veres, the method of contacting pancreatic progenitor or precursor cells with an inhibitor of the IL-4/JAK3 signaling pathway to differentiate the cells into enterochromaffin cells of the claimed invention is not well established. The prior art does not teach contacting pancreatic progenitor cells with an inhibitor of the IL-4/JAK3 signaling pathway to differentiate the cells into NKX6.1 positive and ISL1 negative cells. Therefore, one of skill in the art would neither expect nor predict that contacting pancreatic progenitor cells with an inhibitor of the IL-4/JAK3 signaling pathway would differentiate the cells into NKX6.1 positive and ISL1 negative cells.
The following describes the state of the art with respect to differentiating pancreatic progenitor cells into NKX6.1 positive and ISL1 negative cells in vitro, as identified by Xie et al. (OBM Transplantation 3: 1-20. 2019), Veres et al. (Nature 569: 368-373. 2019), Balboa et al. (eLife 7: 1-35. 2018), and Krentz et al. (Stem Cell Reports 11: 1551-1564. 2018).
Xie evidences that there were three studies that examined and identified enterochromaffin (which Veres describes as being NKX6.1 positive and ISL1-) cells as part of an in vitro differentiation method starting with pluripotent stem cells, Veres, Balboa, and Krentz, respectively. The emergence of this cell population is observed across the 3 differentiation protocols and is marked by FEV and TPH1 expression (page 12, paragraph 1-page 14, paragraph 3).
Veres evidences that SC-EC [stem cell derived enterochromaffin cells) appear during stage 5 culture and differentiate from NEUROG3+ progenitor cells (Figure 1 and Supplemental Figure 1 and page 371, column 2, paragraph 2-page 372, column 1, paragraph 2). As part of Veres’s differentiation protocol, they cultured the stage 5 cells in media comprising XXI, ALK5i, T3, RA, SANT1, and Betacellulin but not an inhibitor of the IL-4/JAK3 signaling pathway (extended Data Table 1).
Xie and Balboa evidence that stage 7 differentiated cells clustered into four different cell populations, expressing markers of β cells, endocrine progenitor cells, α cells, and proliferating α cells (Table 4). The progenitor cell population express enterochromaffin cell markers including DDC, FEV, TPH1, LMX1A (page 13, paragraph 2 of Xie and Supplementary Table 4 of Balboa).
Balboa evidences that their stage 7 media comprises MCDB131 + 2 mM Glutmax + 1.5 g/L NaHCO3 + 2% BSA fV + 20 mM final glucose + 1:200 ITS-X + 10 mg/mL Heparin + 10 mM ALK5inhII + 1 mM GC1 + 10 mM Trolox + 1 mM N-Acetylcysteine (A9165)+75mM Resveratrol (R5010)+20 mM JNK inhibitor (SP600125)+2 mM R428 (S2841) but not an inhibitor of the IL-4/JAK3 signaling pathway (page 24).
Xie and Krentz evidence that the S6d1 [Stage 6 day 1] cells from differentiated human embryonic stem cell line CyT49 were sequenced by Krentz and formed 9 clusters that were classified into 5 cell types: endocrine (Endo), endocrine progenitors (EP) and off-targets including duct, liver, and an unknown cell type. The EP2 cluster contains cells that express genes associated with serotonin production (FEV, DDC and TPH1) which Veres et al. ultimately found give rise to enterochromaffin-like (EC) cells (page 12, paragraph 4 of Xie and Figure 5 of Krentz).
Krentz evidences that they cultured their stage 4 differentiated cells in basal media with 20 mM glucose, 2% BSA, 0.25 µM SANT-1, 0.05 µM retinoic acid, 100 nM LDN193189, 1:200 ITS-X, 1 µM T3, 10 µM Repsox, and 10 µM zinc sulfate for 3 days to generate pancreatic endocrine precursors (Stage 5) but not an inhibitor of the IL-4/JAK3 signaling pathway (page 8, paragraph 1-page 9paragraph 1 of Krentz Supplementary Information and page 1561, column 2, paragraph 5 of Krentz).
Applicant has claimed a method of differentiating pancreatic progenitor into NKX6.1 positive and ISL1 negative cells using an inhibitor of IL-4/JAK3 signaling pathway, yet the specification has not disclosed such methods that definitively produce NKX6.1 positive and ISL1 negative cells and has not set forth in terms of distinguishing identifying characteristics as evidenced by other descriptions of the invention that are sufficiently detailed to show that Applicant was in possession of the claimed method of differentiating pancreatic progenitor cells into NKX6.1 positive and ISL1 negative cells. Furthermore, the state of the art does not teach any methods that use IL-4/JAK3 signaling pathway inhibitors to differentiate pancreatic progenitor cells into NKX6.1 positive and ISL1 negative cells. Therefore, one of skill in the art would neither expect nor predict the claimed method would produce NKX6.1 positive and ISL1 negative cells.
CONCLUSION
Therefore, the Examiner concludes that there is insufficient written description of the instantly claimed method of differentiating pancreatic progenitor cells into NKX6.1 positive and ISL1 negative cells by contacting them with IL-4/JAK3 signaling pathway inhibitors. Specifically, there is limited description of the cells produced by the claimed method which leads to a reasonable question of whether the cells produced by the claimed method are NKX6.1 positive and ISL1 negative cells. As such, the Examiner further concludes a skilled artisan would find the specification inadequately describes the claimed method.
Claim 1-4, 7-14, and 17-18 are rejected under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph, as based on a disclosure which is not enabling. This is a new rejection that is substantially similar to a previous rejection made in response to Applicant’s amendments to claim 1. Any aspect of Applicant’s traversal that is relevant to the rejection as newly written is addressed below.
The disclosure does not enable one of ordinary skill in the art to practice the invention without the identifying the individual culture media involved in the differentiation of pancreatic progenitor cells into NKX6.1 positive and ISL1 negative cells, which is critical or essential to the practice of the invention but not included in the claim(s). See In re Mayhew, 527 F.2d 1229, 188 USPQ 356 (CCPA 1976).
The factors to be weighed to evaluate whether a disclosure satisfies the enablement requirement and whether any necessary experimentation is undue are set forth in MPEP 2164.01(a).
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Although all the factors have been considered, the relevant factors will be addressed below.
Breadth of the claims: Claim 1 recites the following claim language, “A method comprising: contacting a population of cells comprising pancreatic progenitor cells with a composition comprising an inhibitor of IL-4/JAK3 signaling pathway, thereby differentiating said pancreatic progenitor cells into NKX6.1 positive and ISL1 negative cells, wherein: a) said pancreatic progenitor cells are PDX1 and NKX6.1 double positive and are negative for ISL1, Chromogranin A, C-peptide, insulin, glucagon, Arx, or any combination thereof” and b) defining the iIL-4/JAK3 inhibitors. The broadest reasonable interpretation is that this method could be done with any culturing media.
Nature of the invention: The subject matter of the invention relates to a method to differentiate pancreatic progenitor cells into NKX6.1 positive and ISL1 negative cells by contacting them with an inhibitor of IL-4/JAK3 signaling pathway.
State of the prior art: The prior art teaches that a multi-step differentiation procedure is used for generating enterochromaffin cells from pancreatic progenitor cells.
The following describes the state of the art with respect to differentiating pancreatic progenitor cells into at least one type of NKX6.1 +/ISL1- cell type, enterochromaffin cells, in vitro, as identified by Xie et al. (OBM Transplantation 3: 1-20. 2019), Veres et al. (Nature 569: 368-373. 2019), Balboa et al. (eLife 7: 1-35. 2018), and Krentz et al. (Stem Cell Reports 11: 1551-1564. 2018).
Xie evidences that there were three studies that examined and identified enterochromaffin cells as part of an in vitro differentiation method starting with pluripotent stem cells, Veres, Balboa, and Krentz, respectively. The emergence of this cell population is observed across the 3 differentiation protocols and is marked by FEV and TPH1 expression (page 12, paragraph 1-page 14, paragraph 3).
Veres evidences that SC-EC [stem cell derived enterochromaffin cells] appear during stage 5 culture and differentiate from NEUROG3+ progenitor cells (Figure 1 and Supplemental Figure 1 and page 371, column 2, paragraph 2-page 372, column 1, paragraph 2). As part of Veres’s differentiation protocol, they cultured the stage 5 cells in media comprising XXI, ALK5i, T3, RA, SANT1, and Betacellulin and in one protocol included LDN193189 but not an inhibitor of the IL-4/JAK3 signaling pathway (Extended Data Table 1). Veres evidences that changes in the media composition can significantly alter which cells develop at a specific stage (changed the media composition for stages 3 and 4) and at stages downstream of the initial media change (stage 6) (Extended Data Figure 1 and Extended Data Table 1)
Xie and Balboa evidence that stage 7 differentiated cells clustered into four different cell populations, expressing markers of β cells, endocrine progenitor cells, α cells, and proliferating α cells (Table 4 of Xie). The progenitor cell population express enterochromaffin cell markers including DDC, FEV, TPH1, LMX1A (page 13, paragraph 2 of Xie and Supplementary Table 4 of Balboa).
Balboa evidences that their stage 7 media comprises MCDB131 + 2 mM Glutmax + 1.5 g/L NaHCO3 + 2% BSA fV + 20 mM final glucose + 1:200 ITS-X + 10 mg/mL Heparin + 10 mM ALK5inhII + 1 mM GC1 + 10 mM Trolox + 1 mM N-Acetylcysteine (A9165)+75mM Resveratrol (R5010)+20 mM JNK inhibitor (SP600125)+2 mM R428 (S2841) but not an inhibitor of the IL-4/JAK3 signaling pathway (page 24).
Xie and Krentz evidence that the S6d1 [Stage 6 day 1] cells from differentiated human embryonic stem cell line CyT49 were sequenced by Krentz and formed 9 clusters that were classified into 5 cell types: endocrine (Endo), endocrine progenitors (EP) and off-targets including duct, liver, and an unknown cell type. The EP2 cluster contains cells that express genes associated with serotonin production (FEV, DDC and TPH1) which Veres et al. ultimately found give rise to enterochromaffin-like (EC) cells (page 12, paragraph 4 of Xie and Figure 5 of Krentz).
Krentz evidences that they cultured their stage 4 differentiated cells in basal media with 20 mM glucose, 2% BSA, 0.25 µM SANT-1, 0.05 µM retinoic acid, 100 nM LDN193189, 1:200 ITS-X, 1 µM T3, 10 µM Repsox, and 10 µM zinc sulfate for 3 days to generate pancreatic endocrine precursors (Stage 5) but not an inhibitor of the IL-4/JAK3 signaling pathway (page 8, paragraph 1-page 9, paragraph 1 of Krentz Supplementary Information and page 1561, column 2, paragraph 5 of Krentz).
As such, the prior art shows that three different multistep differentiation protocols generate NKX6.1 positive and ISL1 negative enterochromaffin cells through a multistep differentiation protocol from pluripotent stem cells to enterochromaffin cells with enterochromaffin cells only occurring at stage 5 or later and none of the prior art uses an inhibitor of IL-4/JAK3 for differentiating pancreatic progenitor cells into enterochromaffin cells. Additionally, the prior art identifies the importance of the media compositions as the media composition can significantly alter which cells develop at a specific stage. Furthermore, each of the protocols use specific, but different between each protocol, media compositions.
Level of predictability in the art: The prior art has successfully reduced to practice that a multistep differentiation protocol of at least five stages is used to generate NKX6.1 positive and ISL1 negative cells from pluripotent stem cells and none of the prior art uses an inhibitor of IL-4/JAK3 for differentiating pancreatic progenitor cells into enterochromaffin cells. Additionally, the prior art identifies the importance of the media compositions as the media composition can significantly alter which cells develop at a specific stage. Furthermore, each of the protocols use specific, but different between each protocol, media compositions. As such, this results in unpredictability about how someone can use the claimed method to differentiate precursor cells without knowing the media composition.
Amount of direction provided by the inventor and existence of working examples: The Applicant discloses that they cultured a JAK3 inhibitor with stage 5 cells to increase the number of enterochromaffin cells (Example 1). The Example 1 does not provide information about the overall differentiation protocol or media used in generating NKX6.1 positive and ISL1 negative cells. However, paragraph 0096 of the instant specification provides a pancreatic differentiation protocol involving five stages, comprising:
"Stage 1" or "S1" refers to the first step in the differentiation process, the differentiation of pluripotent stem cells into cells expressing markers characteristic of definitive endoderm cells ("DE", "Stage 1 cells" or "S1 cells").
"Stage 2" refers to the second step, the differentiation of cells expressing markers characteristic of definitive endoderm cells into cells expressing markers characteristic of gut tube cells ("GT", "Stage 2 cells" or "S2 cells").
"Stage 3" refers to the third step, the differentiation of cells expressing markers characteristic of gut tube cells into cells expressing markers characteristic of pancreatic progenitor 1 cells ("PP1", "Stage 3 cells" or "S3 cells").
"Stage 4" refers to the fourth step, the differentiation of cells expressing markers characteristic of pancreatic progenitor 1 cells into cells expressing markers characteristic of pancreatic progenitor 2 cells ("PP2", "Stage 4 cells" or "S4 cells"). "Stage 5" refers to the fifth step, the differentiation of cells expressing markers characteristic of pancreatic progenitor 2 cells into cells expressing markers characteristic of pancreatic endoderm cells and/or pancreatic endocrine progenitor cells ("EN", "Stage 5 cells" or "S5 cells").
NKX6.1 positive and ISL1 negative cells are not mentioned in this example protocol but it can reasonably be presumed that the stage 5 of Example 1 refers to this protocol. As stated supra, there is no defined media for stage 5 outside of the addition of the inhibitor of IL-4/JAK3.
Quantity of experimentation needed: In light of the above factors, the prior art discloses that defined media compositions are necessary to generate NKX6.1 positive and ISL1 negative cells from pancreatic progenitor cells. Therefore, these essential steps are considered to be missing from claim 1. As such, there would be undue experimentation related to any culture media to practice the full scope of the claim.
Claims 2-4, 7-14, and 17-18 are also rejected because of their dependency on claim 1.
Response to Arguments
Applicant's arguments filed November 10, 2025, are acknowledged.
Applicant argues that the art teaches several different media compositions for culturing pancreatic progenitor cells to differentiate them into NKX6.1 positive and ISL1 negative cells. Thus, one of skill in the art can predictably use the presently claimed methods and identify appropriate media for culturing the pancreatic progenitor cells. Thus, undue experimentation is not required. Applicant argues that there is a considerable amount of guidance provided in the present specification and that Example 1 and Figure 1 represent a working example that shows the claimed method has been reduced to practice (page 6, paragraph 6-page 9, paragraph 1).
Applicant's arguments have been fully considered but they are not persuasive.
As an initial matter, although Applicant states that there is a considerable amount of guidance provided in the present specification and that Example 1 and Figure 1 represent a working example that shows the claimed method has been reduced to practice, this is not considered to be the case. First, Applicant does not cite to any region of the Specification for this guidance outside of the working examples of Example 1 and Figure 1. It is not clear what Applicant considers the guidance for their claimed method. Second, the working examples leave out crucial information about the media composition, as discussed in the rejection above. No defined media composition is identified for the stage 5 culture conditions. As identified by Veres above, the culture media composition has a significant impact on the cells produced during differentiation. This includes both the stage at which the media may be changed, and downstream stages based on the different cells produced in the earlier stage. As such, the media composition is considered critically important for the claimed method. As there is no media composition identified in the working examples, there is no way to compare the media composition used by the Applicant to what has been used in the art previously and to assess whether the media composition used by the Applicant is a close approximation of what has previously been used or a completely new formulation. Therefore, the media composition is considered critically important for the method of claim 1. Thus, Applicant’s arguments are considered unpersuasive.
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.
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/KEENAN A BATES/Examiner, Art Unit 1631 /JAMES D SCHULTZ/Supervisory Patent Examiner, Art Unit 1631