DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
In reply filed on 1/28/2025, Applicants have amended claim 1, 3, 7-8, 11 and 18, canceled claims 12-14, 19-20, and filed new claim 22.
Currently, claims 1-11, 15-18, and 21-22 are under examination.
Status of the Application
Applicant’s response and amendment filed Jan. 28th, 2025 are acknowledged and entered. Arguments applicable to newly applied rejections to amended or newly presented claims are addressed below. Rejections and/or objections not reiterated from the previous office action are hereby withdrawn due to amendment.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.
Claim Objections
Claim 3 is objected to because of the following informalities: punctuation marks (i.e. comma and semicolon) in claim 3d, line 5. Appropriate correction is required.
New Claim Rejections - 35 USC § 103
As necessitated by amendment
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. 103 (c) for any potential 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103 (a).
Claims 1, 2, 4-11, 15-18 and 21 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Kelly et al. (WO2009/131568A1; cited in IDS filed on Dec. 13, 2019; prior art of record), Benvenisty et al. (WO 2012/070014A2; cited in IDS filed on Dec. 13, 2019), and, Morrison, Gillian M., et al. (Cell Stem Cell 3.4: 402-415, published 2008, cited IDS), Sharivkin et al. (Molecular & Cellular Proteomics, published Sept. 1, 2012; prior art of record) and Iwashita et al. (PLoS One 8.5: e64291, published 2013).
Regarding claim 1 and 2, Kelly et al. teaches a method of purifying a gut endoderm cell derived from a population of pluripotent stem cells (see e.g. claim 1), corresponding to the claim limitation of exposing an initial population of cells that comprises the pancreatic progenitor cells at the anterior definitive endoderm (ADE) stage. Kelly et al. teaches that a ligand, which can be an antibody, agent or fragment, may selectively bind to the targets described in Table 1, on a hES or hES-derived cells (page 41, Table 1). Kelly et al. teaches that the antibodies from Table 1 that may be used either alone or in combination with each other to separate hES-derived endoderm populations at various stages of differentiation (Table 1, page 45, para. 147). Kelly et al. teaches a method of separating the gut endoderm cell from cells derived from pluripotent stem cells (claim 1). Further, Kelly et al. teaches that ligands, agents or antibodies, which selectively bind to the targets (as described in Table 1) are capable of binding to a cell surface receptor on a hES or hES-derived cells, specifically isolating cells from stages (as described in Figure 1) known in the stem cell to endocrine pathway. (page 41, Example 1, Figure 1 and Table 1).
Regarding claim 1, 2 and 21, Kelly et al. teaches the endoderm lineage, including pancreatic endoderm-type cells, derived from human embryonic stem cells (hESCs)(see fig. 1). Kelly et al. teaches the derived pancreatic endoderm cell populations various cell surface markers that are typical for characterizing an indicated cell type derived from hESCs (Figure 1, See schematic representation below, and page 24). More specifically, Kelly et al., teaches the differentiation of the hESCs – (ES) through mesendoderm (ME), ME to definitive endoderm(DE) (DE or PDX1-negative definitive endoderm”)(stage 1), and DE to primitive gut tube (PG or PDX1-negative foregut endoderm”) (stage 2)(see e.g. fig. 1). Kelly et al. discloses the selected surface markers FOXA2, SOX17, and CXCR4, which can be used to enrich or purify the definitive endoderm stage (page 6, para. 49, 63 and 97, See Figure 1). Further, Kelly et al. discloses the endodermal lineage screen, where CD177 is positively expressed at the definitive endoderm (DE) stage, see fig. 1), as well as CER1 as a marker/target (Claim 1, Claim 26, See Table 1, page 41).
Kelly et al. does not explicitly teach the isolation of cells expressing CD177.
However, Benvenisty et al. teaches a method of isolating pancreatic progenitor cells and definite endodermal cells. Benvenisty et al. teaches that the two significant points along the differentiation process for pancreatic progenitor cells are the definitive endoderm (DE) stage, having the expression of SRY box 17 (SOX 17), which is the earliest stage, and the pancreatic progenitor stage, having the pancreatic and duodenal homeobox 1 (PDX1), which is the earliest commitment stages towards the pancreas (page 2, lin. 12-18). Further, the prior art of Sharivkin discloses fractionating unresolved early endoderm compartment of (e.g. CXCR4+) cells and identifies the cell-surface marker CD177 (see e.g. abstract, table 1) from a cell-capture antibody array analysis.
Accordingly, it would have been obvious for a person of ordinary skill in the art to expose an initial population of cells with CER1 and a CD177 ligand as taught by Kelly to isolate the anterior definitive endoderm stage as taught by Benvenisty and Sharivkin in order to obtain the earliest pancreatic progenitor cell stage that is committed toward the pancreas. A person of ordinary skill in the art would have wanted to identify markers that were involved in the anterior definitive endoderm stage (ADE) because Morrison 2008 discloses the need to identify positionally specified populations, such as ADE markers (i.e. CER1), that can be expanded and undergo differentiation towards pancreatic fates (see e.g. abstract, page 402-402). Further, the prior art of Sharivkin et al. teaches that we need more information on progenitor-specific cell surface markers and the resources for determining them are readily available (see e.g. page 593). Additionally, the prior art of Iwashita teaches that was known in the prior art that CER1 is a good marker for quantifying definitive endoderm differentiation (see abstract). Therefore, a person of ordinary skill in the art would have wanted to use CER1 and CD177 to obtain ADE stage EP cells. Furthermore, an artisan of ordinary skill in the art of (i.e. purifying pancreatic progenitor cell populations) 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 4, Kelly et al. discloses that the ligand is an antibody or binding fragment (claim 2).
Regarding claim 5, Kelly et al. discloses a monoclonal antibody (claim 3).
Regarding claim 6, Kelly et al. discloses the detection of an amplified nucleotide acids resulting from PCR primers can be conjugated to a detectable label. (page 27, para. 108)
Regarding claim 7, Kelly et al. discloses a method of quantitating expression of markers that are produced by marker genes is through the use of quantitative PCR (page 27, para 105, 166, and Table 10)
Regarding claims 8 and 10, Kelly et al. discloses that the staining intensity of cells can be monitored by flow cytometry, where lasers detect the quantitative levels of fluorochrome (which is proportional to the amount of cell surface marker bound by specific reagents, e.g. antibodies). Further Kelly et al. discloses that flow cytometry, or FACS, can also be used to separate cell populations based on the intensity of binding to a specific reagent, as well as other parameters such as cell size and light scatter (page 31, para. 115, Examples 2-5; Table 11).
Regarding claim 9, Kelly et al, discloses separating includes affinity chromatography (page 30, para. 114).
Regarding claim 11, Kelly et al. discloses using human embryonic stem cells as the starting material (page 24, para 101).
Regarding claims 15, 16, 17 and 18, Kelly et al. discloses that ligands can be soluble or can be immobilized on the capture medium as indicated by the assay format, e.g., antibody affinity chromatography (page 17, para. 84). Further Kelly et al., discloses the method for enriching, depleting, isolating, separating, sorting and/or purifying the cell population include antibody-coated magnetic beads, affinity chromatography and "panning" with antibody attached to a solid matrix or solid phase capture medium, e.g. plate, column or other convenient and available technique (page 30, para. 114).
Kelly et al., is silent regarding the product cell population comprises at least 50% pancreatic progenitor cells that bind to CD177, express CER1, and are at the ADE stage.
However, Benvenisty et al. teaches that an isolated population of pancreatic progenitor cells, comprising at least about 50% of cells PDX1+ (page 53). Further, the prior art of Morrison discloses the cells expressing “Cer1, Foxa2, and E-cadherin, but not Oct4 (Figure 6C), indicating these cells represent a form of ADE progenitor. To confirm that these cultures were predominantly ADE, we quantitated the percentage of cells expressing these markers and found that 79% (±1.4) expressed Cer1” (page 409, fig. 6)
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).”
In regards to overlapping ranges, MPEP 2144.05(I) states, “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)”, continuing in regards to ranges are close, “Similarly, 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, 783, 227 USPQ 773, 779 (Fed. Cir. 1985)”.
Accordingly, it would have been obvious for one of ordinary skill in the art at the time of the effective filing date to have modified the methods of Kelly to obtain a majority of pancreatic progenitor cells at the anterior definitive endoderm (ADE) as taught by Benvenisty and Morrison with a reasonable expectation of success. A person of ordinary skill in the art would have known that that expresses CER1 (as taught by Kelly and Morrison) with an early endoderm marker like CD177 as taught by Sharivkin because of the need to obtain the earliest stage of pancreatic fate. Furthermore, a person of ordinary skill in the art would have been interested to do so because Sharivkin et al. teaches that more information on progenitor-specific cell surface markers are needed and the resources for determining them (as taught by Iwashita and Kelly) are readily available (See e.g. abstract and discussion). Therefore, a person of ordinary skill in the art would have combined the anterior definitive endoderm (DE) cells with known DE markers like CD177, which would have led to predictable results with a reasonable expectation of success. Further, Iwashita discloses separating cells by using flow cytometry as a multi-step procedure including dissociation of the cells, antibody reaction, and flow cytometry analysis (see e.g. abstract, fig. 3). Therefore, it would have been obvious for a person of ordinary skill in the art to optimize the percentage of cells that bind to a ligand (e.g. CER1 antibody) and cells that do not bind to a ligand and are at the ADE stage (see e.g. page 1). Furthermore, an artisan of ordinary skill in the art of (i.e. methods or purifying cell populations) 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).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claim 3 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Kelly et al. (WO2009/131568A1; cited in IDS filed on Dec. 13, 2019; prior art of record), Benvenisty et al. (WO 2012/070014A2; cited in IDS filed on Dec. 13, 2019), and, Morrison, Gillian M., et al. (Cell Stem Cell 3.4: 402-415, published 2008, cited IDS), Sharivkin et al. (Molecular & Cellular Proteomics, published Sept. 1, 2012; prior art of record) and Iwashita et al. (PLoS One 8.5: e64291, published 2013), as applied to claims 1, 2, 4-17, and 21 above, and further in view of Brafman et al. (“Regulation of endodermal differentiation of human embryonic stem cells through integrin-ECM interactions.” Cell Death Differ, published 2013).
The teachings of Kelly et al., apply here as indicated above.
Regarding claim 3, Kelly et al. teaches that ligands can be soluble or can be immobilized on the capture medium as indicated by the assay format, e.g., antibody affinity chromatography (page 17, para. 84). Further Kelly et al., teaches the method for enriching, depleting, isolating, separating, sorting and/or purifying the cell population include antibody-coated magnetic beads, affinity chromatography and "panning" with antibody attached to a solid matrix or solid phase capture medium, e.g. plate, column or other convenient and available technique (page 30, para. 114).
Regarding claim 3, Kelly et al. does not teach a pancreatic progenitor cell population binding to CD51.
However, Brafman teaches the interactions between integrin receptors and extracellular matrix proteins (ECMPs) are important for the differentiation of human embryonic stem cells (hESC) lines to definitive endoderm (DE) cells, which give rise to internal organs, such as the pancreas (abstract, Figure 3). Brafman et al. teaches HESC-derived DE cells with increased ITGA5 expression were sorted by flow cytometry and differentiated into the PGT stage (stage 3 or posterior foregut, PF or PDX1-positive foregut endoderm)(Figure 5). Further, Brafman et al. teaches that ITGA5 (CD51) and ECMP-integrin interactions are required for hESC differentiation into functionally mature cells (abstract).
Accordingly, it would have been obvious for one of ordinary skill in the art at the time of the invention to employ separating pancreatic progenitor cells by CD51 (an integrin α5 or ITGA5) at various stages based on the methods of Iwashita, Kelly and Sharivkin et al. because CD51 is known to be important in stem cell differentiation and doing so would have isolated the pancreatic progenitor cell population as taught by Brafman. Furthermore, adding the comparative array approach (as taught by Sharivkin et al.) to assess CD51 as a viable marker for pancreatic progenitor cells and using it to purify the pancreatic progenitor cell population (As taught by Iwashita and Kelly) to obtain a product cell population that is enriched relative to the initial population of cells that bind to the ligand, express CER1, and are at the ADE stage and bind to a second ligand (i.e. CD51) would have led to a reasonable expectation of success because Sharivkin et al. would have suggested that a person of ordinary skill to try looking for additional biomarkers for purifying pancreatic progenitor cells, as discussed above. Therefore, a person of ordinary skill in the art would have combined similar cell purification techniques, which would have led to predictable results with a reasonable expectation of success. Furthermore, an artisan of ordinary skill in the art of (i.e. cell culture) 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).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claim 22 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Kelly et al. (WO2009/131568A1; cited in IDS filed on Dec. 13, 2019; prior art of record), Benvenisty et al. (WO 2012/070014A2; cited in IDS filed on Dec. 13, 2019), and, Morrison, Gillian M., et al. (Cell Stem Cell 3.4: 402-415, published 2008, cited IDS), Sharivkin et al. (Molecular & Cellular Proteomics, published Sept. 1, 2012; prior art of record) and Iwashita et al. (PLoS One 8.5: e64291, published 2013), as applied to claims 1, 2, 4-17, and 21 above, and further in view of Cheng, et al., (Cell stem cell 10.4: 371-384; published 2012; cited IDS 12/13/2019).
The teachings of Kelly et al., apply here as indicated above.
Claim 22 is directed providing a population of glucose-responsive β-like cells.
Kelly et al. does not explicitly teach a population of glucose-responsive β-like cells.
However, Cheng discloses the surface marker CD177 in endodermal progenitor (EP) cells and providing a population glucose-responsive pancreatic β-like cells (See e.g. abstract, page 379, 382, fig. 3).
Accordingly, it would have been obvious for a person of ordinary skill in the art to have modified the methods of Iwashita to incorporate the glucose-responsive pancreatic β-like cells as taught by Cheng because Cheng teaches that endodermal progenitor (EP) cells-derived β-cells are “functionally responsive to the physiologic stimulus (D-glucose) for insulin release in a manner similar to that of adult islets in vitro” (page 379). Furthermore, it would have been obvious to combine prior art elements according to known methods to yield predictable results. Incorporating the Ep cells as taught by Cheng would have led to predictable results with a reasonable expectation of success because both teach the characteristics of definitive endoderm cells. Furthermore, Cheng teaches that EP cells represent a powerful tool to study endoderm specification and offer a potentially safe source of endodermal-derived tissues for transplantation therapies (see abstract). Therefore, incorporating the endodermal progenitor lines as taught by Cheng with the methods of definitive endoderm differentiation as Iwashita would have led to predictable results with a reasonable expectation of success. Furthermore, an artisan of ordinary skill in the art of (i.e. definitive endoderm differentiation) 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).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Response to Arguments
Applicant’s arguments filed 1/28/2025 are acknowledged. The arguments have been fully considered but they are not persuasive.
Applicant traverses the rejection of claims 1-11, 15-18 and 21 as failing to comply with the enablement requirement. Applicant asserts that the “inventors demonstrate that the surface marker CD 177 can be used to overcome the substantial functional heterogeneity of the ADE in vitro, enabling the sorting of specified organ progenitors at the endoderm stage, and shows that the claimed methods can provide an improved cell population for subsequent differentiation, maturation and function of SC-β-like cells in vitro. Further, Applicant asserts that the claims encompass a method of purification of pancreatic progenitor cell population at the stage of anterior definitive endoderm (ADE) using the surface marker CD177, wherein the pancreatic progenitors express CER1. (Remarks pages 6-10).
Applicant’s arguments with respect to the previous rejection has been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Kelly et al. (WO2009/131568A1; cited in IDS filed on Dec. 13, 2019; prior art of record), Benvenisty et al. (WO 2012/070014A2; cited in IDS filed on Dec. 13, 2019), and, Morrison, Gillian M., et al. (Cell Stem Cell 3.4: 402-415, published 2008, cited IDS), Sharivkin et al. (Molecular & Cellular Proteomics, published Sept. 1, 2012; prior art of record) and Iwashita et al. (PLoS One 8.5: e64291, published 2013), as applied to claims 1, 2, 4-17, and 21 above, and further in view of Cheng, et al., (Cell stem cell 10.4: 371-384; published 2012; cited IDS 12/13/2019).
Applicant asserts that “it should be noted that, in vivo, high TGF-β/Nodal activity promotes the anterior ADE fate, while lower Nodal signaling strength, Bmp signaling from the extra-embryonic region and high canonical Wnt/β-catenin signaling at the posterior side specifies posterior fates (see, e.g., Vincent, S. D., Cell fate decisions within the mouse organizer are governed by graded Nodal signals. Genes Dev., 2003). In this regard, the present inventors observed higher expression of CER1, a Nodal, Bmp and Wnt signaling antagonist, in CD177+ ADE pancreatic progenitors, which is suggestive of an active auto-regulatory feedback loop modulating ligand receptor interactions in these cells and thus fine-tuning the morphogen requirements to maintain the anterior characteristic and fate specification of the CD 177+ ADE pancreatic progenitors” (Remarks, page 8).
Applicant’s arguments with respect to the previous rejection has been fully considered and are persuasive. Therefore, the rejection has been withdrawn. Examiner is thankful for the prior art of Vincent, 2003, and its disclosure of the Nodal signal to anterior definitive endoderm. However, the Examiner would like to note that the claims do not recite a “higher expression of CER1, a Nodal, Bmp and Wnt signaling antagonist, in CD177+ ADE pancreatic progenitors” as stated above. Therefore, the claims are broadly interpreted a pancreatic progenitor cell population being capable of being to CER1 and CD177 and thus, being at the anterior definitive endoderm stage, as discussed above. As states supra, upon further consideration, a new ground(s) of rejection is made in view of Kelly et al. (WO2009/131568A1; cited in IDS filed on Dec. 13, 2019; prior art of record), Benvenisty et al. (WO 2012/070014A2; cited in IDS filed on Dec. 13, 2019), and, Morrison, Gillian M., et al. (Cell Stem Cell 3.4: 402-415, published 2008, cited IDS), Sharivkin et al. (Molecular & Cellular Proteomics, published Sept. 1, 2012; prior art of record) and Iwashita et al. (PLoS One 8.5: e64291, published 2013), as applied to claims 1, 2, 4-17, and 21 above, and further in view of Cheng, et al., (Cell stem cell 10.4: 371-384; published 2012; cited IDS 12/13/2019).
Applicant asserts that “the inventors further discovered that the endoderm is inherently heterogeneous and, depending upon the signaling it receives, is patterned by intrinsic and extrinsic cues that form distinct organ progenitors, i.e. pancreatic progenitors” (Remarks, page 8). Further, Applicant argues that “the specification also demonstrates increased expression of β cell maturation marker MAFA and GLUT1 in CD 177+ ADE-derived β -like cells. The significantly higher expression of these markers in CD177+ cell-derived β -like cells, compared to CXCR4+ cells-derived β -like cells, demonstrates that the isolation of pancreatic-specified CD 177+ ADE progenitors promote more homogenous differentiation towards β -like cells when compared to heterogeneous CXCR4+ bulk ADE (see FIG. 13E)” (Remarks, page 10).
Applicant’s arguments with respect to the previous rejection has been fully considered and are persuasive. Therefore, the rejection has been withdrawn.
As discussed above, Examiner is thankful for the note and explanation of significantly higher expression of these markers in CD177+ cell-derived β -like cells, compared to CXCR4+ cells-derived β -like cells. However, the Examiner would like to note that the breadth of the claims encompasses the binding CER1 and CD177, as disclosed in claim 1, and as discussed above in the obviousness rejection. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
As states supra, upon further consideration, a new ground(s) of rejection is made in view of Kelly et al. (WO2009/131568A1; cited in IDS filed on Dec. 13, 2019; prior art of record), Benvenisty et al. (WO 2012/070014A2; cited in IDS filed on Dec. 13, 2019), and, Morrison, Gillian M., et al. (Cell Stem Cell 3.4: 402-415, published 2008, cited IDS), Sharivkin et al. (Molecular & Cellular Proteomics, published Sept. 1, 2012; prior art of record) and Iwashita et al. (PLoS One 8.5: e64291, published 2013), as applied to claims 1, 2, 4-17, and 21 above, and further in view of Cheng, et al., (Cell stem cell 10.4: 371-384; published 2012; cited IDS 12/13/2019).
Applicant argues regarding the prior art of record that Kelly is relating to the expression of CD177 at stages 2/4/5 and not the anterior definitive endoderm stage (ADE), and Cheng discloses CD177/NB1 are expressed differently between endoderm progenitor (EP) cells and transient endoderm cells (i.e. stages S0 and S1 of DE) and does not contradict the methods as presently claimed (Remarks, pages 11-12).
The arguments have been fully considered but deemed unpersuasive. The detailed reason for obviousness is set forth in the previous office action and above. In response, the applicant is not considering the breadth of the newly amended claim 1. In response to the arguments directed at Kelly and Cheng is not persuasive because the references are no longer cited for teaching the anterior definitive endoderm stage (see of Iwashita et al.), as discussed above, the claims are broadly interpreted a pancreatic progenitor cell population being capable of being to CER1 and CD177 and thus, being at the anterior definitive endoderm stage.
As states supra, upon further consideration, a new ground(s) of rejection is made in view of Kelly et al. (WO2009/131568A1; cited in IDS filed on Dec. 13, 2019; prior art of record), Benvenisty et al. (WO 2012/070014A2; cited in IDS filed on Dec. 13, 2019), and, Morrison, Gillian M., et al. (Cell Stem Cell 3.4: 402-415, published 2008, cited IDS), Sharivkin et al. (Molecular & Cellular Proteomics, published Sept. 1, 2012; prior art of record) and Iwashita et al. (PLoS One 8.5: e64291, published 2013), as applied to claims 1, 2, 4-17, and 21 above, and further in view of Cheng, et al., (Cell stem cell 10.4: 371-384; published 2012; cited IDS 12/13/2019).
Applicant argues regarding the prior art of record that Benvenisty et al. does not teach CER1 and the prior art of Kelly et al., does not provide guidance to the ADE stage. (Remarks, page 11-12). Further, Applicant argues that Cheng does not specify CD177 at the ADE stage. Applicant notes that the “present invention relates to purification of pancreatic progenitor cells using CD177 at the ADE stage (stage SI), i.e. at a later stage than described in Cheng et al.” (Remarks, page 12).
The arguments have been fully considered but deemed unpersuasive. The detailed reason for obviousness is set forth in the previous office action and above.
In response to the prior art of Benvenisty et al., the Examiner views Benenistry for disclosing CER1 and CD177. Further, the prior art of Morrison discloses the cells expressing “Cer1, Foxa2, and E-cadherin, but not Oct4 (Figure 6C), indicating these cells represent a form of ADE progenitor”. Therefore, it was well known in the art that CER1 identified ADE stage. Additionally, Cheng is cited for discloses the surface marker CD177 in endodermal progenitor (EP) cells and providing a population glucose-responsive pancreatic β-like cells (See e.g. abstract, page 379, 382, fig. 3). Further, the arguments regarding prior art of and Kelly et al., are not persuasive[AltContent: textbox ([img-media_image1.png]
Kelly et al. Fig. 1)], see CD177 is positively expressed at stage 2 (endodermal lineage screen)(page 44, para. 145 and 146, Table 1), and the marker of CER (i.e. CER1, see page 23, par. 97) are expressed in definitive endoderm cells (see e.g. abstract, page 9, para. 63; Figure 1).
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."
In response to applicant's argument, a 35 U.S.C. § 103(a) based test for obviousness is not whether the features of a secondary reference may be 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).
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
As states supra, upon further consideration, a new ground(s) of rejection is made in view of Kelly et al. (WO2009/131568A1; cited in IDS filed on Dec. 13, 2019; prior art of record), Benvenisty et al. (WO 2012/070014A2; cited in IDS filed on Dec. 13, 2019), and, Morrison, Gillian M., et al. (Cell Stem Cell 3.4: 402-415, published 2008, cited IDS), Sharivkin et al. (Molecular & Cellular Proteomics, published Sept. 1, 2012; prior art of record) and Iwashita et al. (PLoS One 8.5: e64291, published 2013), as applied to claims 1, 2, 4-17, and 21 above, and further in view of Cheng, et al., (Cell stem cell 10.4: 371-384; published 2012; cited IDS 12/13/2019).
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