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 .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 12-23-2025 has been entered.
Applicant's amendments to the claims and arguments filed on 12-23-2025 have been received and entered. Claims 1 and 18 have been amended. Claim 21 has been added. Claims 9-10, 14, 16-17, 19 have been canceled. Claims 1-8, 11-13, 15, 18, 20-21 are pending and under consideration.
Priority
This application claims priority from US provisional application No 63/209,435 filed on 06/11/2021.
Maintained in modified form-Claim Rejections - 35 USC § 103 - necessitated by amendments
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1, 3-8, 13, 15, 18 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Agulnick et al (Pub. No .: US 2020/0281987 A1, Pub. Date: Sep. 10, 2020) in view of Schulz (EP2730649A1, Date of publication: 14.05.2014) and Jerums et al. (WO 2014/022102 Al, International Publication Date: 6 February 2014).
Claim interpretation:
As per MPEP 2111.03, “The transitional phrase "consisting essentially of" limits the scope of a claim to the specified materials or steps "and those that do not materially affect the basic and novel characteristic(s)" of the claimed invention. …… For the purposes of searching for and applying prior art under 35 U.S.C. 102 and 103, absent a clear indication in the specification or claims of what the basic and novel characteristics actually are, "consisting essentially of" will be construed as equivalent to "comprising." See, e.g., PPG, 156 F.3d at 1355, 48 USPQ2d at 1355….. If an applicant contends that additional steps or materials in the prior art are excluded by the recitation of "consisting essentially of," applicant has the burden of showing that the introduction of additional steps or components would materially change the characteristics of the claimed invention. In re De Lajarte, 337 F.2d 870, 143 USPQ 256 (CCPA 1964). See also Ex parte Hoffman, 12 USPQ2d 1061, 1063-64 (Bd. Pat. App. & Inter. 1989)”
In the instant case, the specification of the claimed invention teaches that “As used herein, the term "consisting essentially of" takes it's well established meaning and is generally construed to mean that the composition or formulation (a) necessarily includes the listed ingredients and (b) is open to unlisted ingredients that do not materially affect the basic and novel properties of the composition (e.g. resulting in high-recovery yields of cryopreserved SC-islets; improved islet health resulting in improved function; high-recovery yield of resized SC-islets; improved cell recovery and clustering morphology; improved gene expression for SC Islets and maintains Beta cell identity; maintenance of C-peptide and NKX6-1; increase in INS or MAFA gene expression; or maintain insulin expression after thaw relative to standard techniques)” ([0063], page 22). Thus, “consisting essentially of” will be interpreted as equivalent to “comprising” and open to unlisted ingredients that do not materially affect the basic and novel properties of the composition.
Regarding to claim 1, preamble and step (a), Agulnick et al teach that “still other embodiments of the invention provide for methods of producing cell aggregate suspensions formed from differentiated pluripotent stem cell cultures” ([0107], page 20). Agulnick et al teach cryopreserving and thawing pancreatic endoderm cell (PEC) aggregates: “Here , Applicant explored various cryopreservation conditions to optimize cell survival following cryopreservation …… These many iterative experiments were tested alone, or in combination , to determine how cell survival following cryopreservation could be optimized . Such optimized cryopreservation and thawing protocols produce PEC aggregates with optimized cell survival following cryopreservation.”(Example 1, [0215]-[0216], page 33-34). Agulnick et al teach that after cryopreservation , the cells can be thawed through any available method ([0157], page 26), and any media can be used for diluting the cryopreservation solution which is in contact with the thawed cells ([0158], page 26). Agulnick et al teach cryopreservation techniques can be utilized with PEC derived from other cell types such as iPEC (PEC aggregates derived from induced pluripotent stem cells) , or PEC made from other pluripotent stem cells ([0213], page 33). Agulnick et al teach “pancreatic islet hormone -expressing cell,” “ pancreatic endocrine cell ,” or equivalents thereof refer to a cell , which has been derived from a pluripotent cell in vitro, which can be polyhormonal or singly hormonal ([0082], page 8).
Regarding to claim 1, step (b) and (c): Agulnick et al teaches any media can be used for diluting the cryopreservation solution which is in contact with the thawed cells ([0158], page 26). The cells are mixed with compounds during thawing or during flushing (dilution media ), or during a post thaw incubation period (incubation media) at sufficient concentrations to stabilize and protect cell membranes from damage post-thaw. For example: “DMEM containing media …… Another suitable additive includes DNase …… a serum protein such as albumin …… D -glucose…… L-glutamine …… antibiotic …… anti -apoptotic agents, a composition that inhibits apoptosis …… Bcl-2 (Mitochondrial Anti -apoptotic protein )” ([0276], Page 42).
PNG
media_image1.png
909
756
media_image1.png
Greyscale
Furthermore, Agulnick et al stated that “Applicant explored various cryopreservation conditions to optimize cell survival following cryopreservation” ([0216], page 33) and “It will be apparent to one skilled in the art that varying substitutions, modifications or optimization, or combinations may be made to the embodiments disclosed herein without departing from the scope and spirit of the invention” ([0285], page 43). Agulnick et al teach DMEM containing media comprising different factors and “or others additives as are well known in the art”. Thus, it is a matter of choice to include or exclude DNAse I and anti -apoptotic agents as taught by Agulnick et al.
Although Agulnick et al teach the use of DNAse at 25 ug/mL in rotation culture for 3 or 4 days for a post thaw incubation in incubation medium ([0225], page 35), Agulnick et al do not specifically teaches at least one trace element and 0.1 mg/ml to 10 mg/ml of a deoxyribonuclease I (DNAse I), and culturing for about 24 hours. However, Schulz cures the deficiency.
Schulz teaches cellular composition of pancreatic endoderm cells (PEC) and pancreatic cells derived from human pluripotent stem cells ([0019], page 4). The composition can comprise trace elements such as ZnSO4 ([0139], page 21). Schulz teaches that some of the spheres continued to aggregate over the course of the culture to limit this continued aggregation, 38 µg/mL DNase I was included in some suspension cultures for the first 24 hours ([0249], page 46). Schulz also teaches the use of DNase of 50-100 µg/mL ([0299], page 54) (Note: 100 µg/mL = 0.1mg/mL), and addition of an apoptosis inhibitor in suspension culture (Example 15, page 47).
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the rejected claims to combine the teachings of prior art to modify the method of Agulnick et al by using trace element and 0.1mg/mL DNase I in the medium for culturing for 24 hours as taught by Schulz, as instantly claimed, with a reasonable expectation of success. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would have been motivated to optimize teachings of Agulnick et al of using DNAse at concentration of 25 µg/mL with teachings of Schulz of using DNAse at concentration of 100 µg/mL out of the course of routine optimization (MPEP 2144.05 (II) (A)) and because Schulz provides explicit advantage of improved methods for the stable large-scale expansion of hESC, including enzymatic passaging ([0004], page 2) and added cell survival agents that can increase survival of cell populations leading to improved recovery of the cells ([0106], page 15, lines 29-37). One of skill in the art would have been expected to have a reasonable expectation of success because Schulz was successful in generation of pancreatic lineages that have been derived from hESC. Schulz also provides detailed instructions with working examples and data for generating such cells.
Although Agulnick et al teach that anti -apoptotic agents, a composition that inhibits apoptosis and /or necrosis triggered by cryopreservation can be added to the cells ([0276], page 42), Agulnick et al do not teach using BI-6C9 (apoptosis inhibitor). However, Jerums et al cure the deficiency.
Jerums et al teach a method of modulating the viability the cells of a cell culture with the one or more anti-apoptotic compound comprises one or more of BI-6C9 etc. (Page 2, line 26-35). Jerums et al. teach Figure 1 showing the use of BI-6C9 up to 12 days. Thus, a person of ordinary skill in the art would be able to use BI-6C9 as an anti-apoptotic compound any amount of time up to 12 days.
PNG
media_image2.png
1012
1306
media_image2.png
Greyscale
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the rejected claims to combine the teachings of prior art to modify the method of Agulnick et al by using BI-6C9 as anti-apoptotic compound as taught by Jerums et al as instantly claimed, with a reasonable expectation of success. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would have been motivated to do so because Jerums et al teaches that various compounds targeting different apoptotic mechanisms were identified, and these compounds were found to improve cell viability and productivity (Page 6, lines 1-2). One of ordinary skill in the art would have had a reasonable expectation of success in doing so because Jerums et al teaches that the compounds were observed to be effective in reducing the loss of cell viability with improved productivity in fed-batch cultures expressing an antigen binding protein of interest (Page 6, lines 5-7).
Regarding to claim 3, Schulz teaches that amino acids can be added to the defined media. Non-limiting examples of such amino acids are …. L-Alanyl-L-Glutamine … ([0140], page 21)
Regarding to claim 4, Schulz teaches that the medium may contain a variety of components including P/S (penicillin/streptomycin) ([0207], page 40).
Regarding to claim 5, Schulz teaches the compositions and methods of the present invention comprise serum albumin (SA). In specific embodiments, the SA is either bovine SA (BSA) or human SA (HAS) ([0169], page 25).
Regarding to claim 6-7, Agulnick et al teaches the use large stable molecules such as Dextran and / or D-glucose can be added to the media ([0276], page 42).
Regarding to claim 8, Schulz teaches the composition can further comprise trace elements …. ZnSO4 ([0139], page 21).
Regarding to claim 13 and 15, Agulnick et al teaches the incubation period (whether cryopreserved or not) increases the total percentage of endocrine cells plus non -endocrine cells increases whereas the “ residual” cells decrease . The above results are surprising because previously it has been shown that cryopreservation of hESCs causes extensive cell death . Thus, increased cell survival of PEC without substantially changing the overall cellular composition or population is an important feature of the above protocol ([0230], page 36).
Regarding to claim 18, Schulz teaches the present invention also relates to kits ([0214], page 41). The kits of the invention may contain virtually any combination of the components set out above or described elsewhere herein. As one skilled in the art would recognize, the components supplied with kits of the invention will vary with the intended use for the kits. Thus, kits may be designed to perform various functions set out in this application and the components of such kits will vary accordingly ([0215], page 41). The teachings for “apoptosis inhibitor comprising BI-6C9” are as described above.
Regarding to claim 21, Agulnick et al teach endocrine precursor cell can further differentiate into cells of the endocrine system including, but not limited to , pancreatic islet hormone-expressing cells ([0081], page 8). Pancreatic islet hormone-expressing cells can be mature or immature pancreatic islet hormone-expressing cells ([0082], page 8). The cells may be incubated in incubation medium for up to 1 hour, 2 hours , 3 hours, 4 hours, 5 hours , 10 hours, 24 hours , 48 hours, 72 hours, 4 days, 5 days, 6 days, 7 days , 8 days, 9 days , 10 days or longer ([0270], page 42).
Claims 2, 11, 12 are rejected under 35 U.S.C. 103 as being unpatentable over Agulnick et al (Pub. No .: US 2020/0281987 A1, Pub. Date: Sep. 10, 2020) in view of Schulz (EP2730649A1, Date of publication: 14.05.2014) and Jerums et al. (WO 2014/022102 Al, International Publication Date: 6 February 2014) as applied to claims 1, 3-8, 13, 15, 18, 21 above, and further in view of Srivatsava et al (biorxiv, doi: 10.1101/656785, May 31, 2019 (Applicant own work)
The teachings of Agulnick et al, Schulz and Jerums et al are as above and are incorporated herein in their entirety. Agulnick et al, Schulz and Jerums et al do not teach the basal medium is MCDB 131. Srivatsava et al cure the deficiency.
Regarding to claim 2, Srivatsava et al teaches islet/SC-β cells culture and medium: “hESCs were differentiated to SC-β cells …… Stage 1 base media was: 500 mL MCDB 131” (Page 15).
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the rejected claims to combine the teachings of prior art to modify the method of the references above by using MCDB 131 as taught by Srivatsava et al as instantly claimed, with a reasonable expectation of success. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would have been motivated to do so because Srivatsava et al teaches that SC-β cells generated with their protocol exhibits strong glucose-stimulated insulin secretion. This function correlates with increases in islet-like mitochondrial respiration and cytoplasmic calcium levels in response to high glucose stimulation (Page 11, conclusion). One of ordinary skill in the art would have had a reasonable expectation of success in doing so because Srivatsava et al was successful in generation of SC-β cells by using their protocol.
Regarding to claim 11-12, the teachings of components of the first and second medium are as described above.
Claims 20 is rejected under 35 U.S.C. 103 as being unpatentable over Agulnick et al (Pub. No .: US 2020/0281987 A1, Pub. Date: Sep. 10, 2020) in view of Schulz (EP2730649A1, Date of publication: 14.05.2014) and Jerums et al. (WO 2014/022102 Al, International Publication Date: 6 February 2014) as applied to claims 1, 3-8, 13, 15, 18, 21 above, and further in view of Roche (Product Information Sheet-11284932001, Cat. No. 11 284 932 001 , Version: 19 Content Version: December 2020).
The teachings of Agulnick et al, Schulz and Jerums et al are as above and are incorporated herein in their entirety. The above references do not teach 1 mg/ml DNase.
Regarding to claim 20, Roche teaches Reconstitution of DNase I: Reconstitute in sterile, double-distilled water to a final concentration of 10 mg/ml. DNase I can be used in several applications: Prevents unwanted cell clumping during tissue disaggregation procedures and during cell culture since it is included in the medium. Has been proven to be non-cytotoxic in concentrations up to 1 mg/ml (see page 3, items 1.2 to 1.3). Working Concentration: Use 0.01 to 1 mg/ml DNase I (Page 5, item 2.2).
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the rejected claims to combine the teachings of prior art to modify the method of the references above by using 1 mg/ml DNase I as taught by Roche as instantly claimed, with a reasonable expectation of success. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would have been motivated to do so because Roche teaches DNase I can be used to prevents unwanted cell clumping during tissue disaggregation procedures and during cell culture since it is included in the medium. One of ordinary skill in the art would have had a reasonable expectation of success in doing so because DNase I has been proven to be non-cytotoxic in concentrations up to 1 mg/ml.
Response to Arguments
Applicant's arguments filed on 12-23-2025 have been fully considered but they are not persuasive.
1. Applicants argue unexpected result:
conventional medium causes undesirable cell clumping after thawing pluripotent SC islet cells. Using a medium comprising DNase I and the apoptosis inhibitor Bl-6C9 for about 24 hours after thawing SC islet cells reduces cell clumping, recovery and clustering morphology. 1 As shown in FIGs. 2A-2B of the application, the method disclosed by the pending claims improved the quality of the pluripotent SC islet cells after thawing. The SC islet cells further exhibit improved gene expression and maintenance of beta cell identity. 2 These results could not have been expected from the cited publications and outweigh any prima facie obviousness of the claims (Remarks, page 6-8).
Response to Arguments:
As per MPEP 716.02, Any differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In the instant case, there is no evidence of record that specifically using DNase I and the apoptosis inhibitor Bl-6C9 for about 24 hours would leads to unexpected results over prior arts. Agulnick et al teach any media during a post thaw incubation period comprising anti -apoptotic agents, a composition that inhibits apoptosis ([0276], Page 42), and the use of DNAse at 25 ug/mL for a post thaw incubation in incubation medium ([0225], page 35). Additionally, Schulz teaches cell aggregation of pancreatic islet cells with the use of 38 µg/mL DNase I included in some suspension cultures for the first 24 hours ([0249], page 46) and addition of an apoptosis inhibitor in suspension culture (Example 15, page 47). Also, Jerums et al teach a method of modulating the viability the cells of a cell culture with the one or more anti-apoptotic compound comprises one or more of BI-6C9 etc. (Page 2, line 26-35). Jerums et al teach Figure 1 showing the use of BI-6C9 up to 12 days. Thus, a person of ordinary skill in the art would be able to use BI-6C9 as an anti-apoptotic compound any amount of time up to 12 days.
Applicant cited instant disclosure of FIGs. 2A-2B and FIGs. 3A-3B (see below) to state that improved the quality of the pluripotent SC islet cells after thawing over a control media S6 (in Figure 2) and M6 (in figure 3). However, the specification does not specify what components is/are included or excluded in the control and how it is different from the teachings of prior arts. It is not unexpected over prior arts if the identity of control media in the comparison is not specified to compare with the prior art. The figure 3A does not appear to have statistical analysis. It is unclear if there is only 1 replicate or multiples replicates for the experiment.
PNG
media_image3.png
1100
564
media_image3.png
Greyscale
PNG
media_image4.png
983
638
media_image4.png
Greyscale
It is also noted that it appears both Figure 2 and 3 above specify S6 as a control in both figures but the texts in [0015]-[0016] specify that the control in FIGs. 2A-2B is S6 and the control in FIGs. 3A-3B is standard control M6 media (see below). It is unclear if these two controls (control S6 media vs standard control M6 media) are the same or different (see below).
PNG
media_image5.png
404
873
media_image5.png
Greyscale
Nevertheless, Agulnick et al stated that “Thawing and incubation conditions analyzed include , but are not limited to optimization of the concentrations, time of use and duration of the thawing and incubation media , and treatment with other factors in the thawing and incubation media for improving cell survival …. Such optimized thawing and incubation protocols produce PEC aggregates with optimized cell survival following cryopreservation.” ([0246], page 38). Thus, optimized thawing and incubation protocols taught by Agulnick et al are expected to result in improved the quality of
the aggregates after thawing.
2. Applicants argue that:
Agulnick merely discloses the use of DNase or an apoptosis inhibitor as one of many additives that can be used in the medium during thawing. Consequently, Agulnick does not teach or suggest contacting thawed pluripotent SC-islet cells for about 24 hours in a first medium with DNase in a combination with apoptosis inhibitor Bl-6C9, followed by contacting the cells with a second medium consisting essentially of basal medium, at least one glutamine alternative, at least one antibiotic, one or more albumin, at least one energy substrate, and at least one trace element, as required by the claims. Without any suggestion or guidance to include a combination of DNAse and B1-6C9 in a medium for thawing pluripotent SC-islet cells, a person of ordinary skill in the art would not have expected that using DNase and as recited in the claims would lead to reduced cell clumping.
The Examiner considers Schulz as teaching using DNAse I in a suspension culture for 24 hours. However, Schulz does not teach or suggest culturing thawed pluripotent SC islet cells. Schulz teaches aggregation of a progenitor cell as one of the steps in its differentiation process.
Schulz teaches that adding DNAse I causes the aggregates to be harder to break up when splitting. Therefore, Schulz fails to teach or suggest using DNAse I for use in a medium for culturing thawed SC-islet cells. Further, Schulz does not teach the use of apoptosis inhibitor in combination with DNAse I. Schulz would not have led a person of ordinary skill in the art to predict that using these reagents to thaw SC-islet cells would have reduced cell clumping.
Jerums merely teaches modulating the properties of a cell culture expressing a protein of interest by adding an anti-apoptotic compound to growing cell cultures and discloses several examples of anti-apoptotic compounds including Bl-6C9.
Srivatsava merely characterizes in vitro function of SC-β cells generated with a differentiation protocol. Srivatsava does not teach or suggest DNAse in a combination with Bl-6C9 for about 24 hours, for culturing thawed Sc-islet cells (Remarks, page 7-8).
Response to Arguments:
It appears that Applicant is arguing that the cited references do not expressly suggest the claimed invention. However, it is well established in case law that a reference must be considered not only for what it expressly teaches, but also for what it fairly suggests. In re Burkel, 201 USPQ 67 (CCPA 1979). Furthermore, in the determination of obviousness, the state of the art as well as the level of skill of those in the art are important factors to be considered. The teaching of the cited references must be viewed in light of these factors. It also appears that applicant is attempting to attack each reference individually. However, in a 103 rejection the references must be considered as a whole. Applicants have also engaged in selective reading of the teachings of the cited prior art to formulate the grounds for no motivation to combine.
In the instant case, as described above, Agulnick et al teach any media during a post thaw incubation period comprising anti -apoptotic agents, a composition that inhibits apoptosis ([0276], Page 42), and the use of DNAse at 25 ug/mL for a post thaw incubation in incubation medium ([0225], page 35). Additionally, Schulz teaches cell aggregation of pancreatic islet cells with the use of 38 µg/mL DNase I included in some suspension cultures for the first 24 hours ([0249], page 46) and addition of an apoptosis inhibitor in suspension culture (Example 15, page 47). Also, Jerums et al teach a method of modulating the viability the cells of a cell culture with the one or more anti-apoptotic compound comprises one or more of BI-6C9 etc. (Page 2, line 26-35). Jerums et al teach Figure 1 showing the use of BI-6C9 up to 12 days. Thus, a person of ordinary skill in the art would be able to use BI-6C9 as an anti-apoptotic compound any amount of time up to 12 days. Srivatsava et al teaches islet/SC-β cells culture and medium: “hESCs were differentiated to SC-β cells …… Stage 1 base media was: 500 mL MCDB 131” (Page 15).
One of ordinary skill in the art would have been motivated to combine teachings of Schulz because:
Schulz provides explicit advantage of improved methods for the stable large-scale expansion of hESC, including enzymatic passaging ([0004], page 2) and added cell survival agents that can increase survival of cell populations leading to improved recovery of the cells ([0106], page 15, lines 29-37).
Jerums et al teaches that various compounds targeting different apoptotic mechanisms were identified, and these compounds were found to improve cell viability and productivity (Page 6, lines 1-2).
Srivatsava et al teaches that SC-β cells generated with their protocol exhibits strong glucose-stimulated insulin secretion. This function correlates with increases in islet-like mitochondrial respiration and cytoplasmic calcium levels in response to high glucose stimulation (Page 11, conclusion).
Applicant also argue that Schulz teach adding DNAse I causes the aggregates to be harder to break up when splitting and Schulz would not have led a person of ordinary skill in the art to predict that using these reagents to thaw SC-islet cells would have reduced cell clumping. It is noted that Schulz clearly suggest to use DNAse I to control aggregation: “Some of the spheres continued to aggregate over the course of the culture, as some aggregates became much larger than the majority. ….. To limit this continued aggregation, 38 mg/mL DNaseI was included in some suspension cultures for the first 24 hours. This approach appeared to be conducive to the initial aggregation, with relatively larger, but fewer, aggregates formed in the presence of DNaseI” ([0249], page 46). Thus, it is clear that Schulz suggest the use DNAse I to control the forming of aggregates. Also, as per MPEP 2112(II), There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003) (rejecting the contention that inherent anticipation requires recognition by a person of ordinary skill in the art before the critical date and allowing expert testimony with respect to post-critical date clinical trials to show inherency); see also Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004) ("[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention."); Abbott Labs v. Geneva Pharms., Inc., 182 F.3d 1315, 1319, 51 USPQ2d 1307, 1310 (Fed. Cir. 1999)
Schulz teaches that some of the spheres continued to aggregate over the course of the culture to limit this continued aggregation, 38 µg/mL DNase I was included in some suspension cultures for the first 24 hours ([0249], page 46). Schulz also teaches the use of DNase of 50-100 µg/mL ([0299], page 54) (Note: 100 µg/mL = 0.1mg/mL), and addition of an apoptosis inhibitor in suspension culture (Example 15, page 47). Thus, Schulz does teach the use of apoptosis inhibitor in combination with DNAse I.
3. Applicants argue that:
As amended claim 1 limits the scope of the second medium, which further defines the specific steps the thawed SC-Islet cells are treated with after contact with a combination of DNase and apoptosis inhibitor. Specifically, as discussed above, the cited publications do not lead to a reasonable expectation that culturing thawed pluripotent SC-islet cells in the presence of a first medium comprising DNAse I and BI-6C9 for about 24 hours and contacting the cells with a second medium without the DNAse I and Bl-6C9 reduces cell clumping (Remarks, page 8-9).
Response to Arguments:
The language of step c in base claim 1 is not limiting to exclude the use of DNAse I and BI-6C9 in second medium. In the instant case, the specification of the claimed invention teaches that “As used herein, the term "consisting essentially of" takes it's well established meaning and is generally construed to mean that the composition or formulation (a) necessarily includes the listed ingredients and (b) is open to unlisted ingredients that do not materially affect the basic and novel properties of the composition (e.g. resulting in high-recovery yields of cryopreserved SC-islets; improved islet health resulting in improved function; high-recovery yield of resized SC-islets; improved cell recovery and clustering morphology; improved gene expression for SC Islets and maintains Beta cell identity; maintenance of C-peptide and NKX6-1; increase in INS or MAFA gene expression; or maintain insulin expression after thaw relative to standard techniques)” ([0063], page 22). Thus, “consisting essentially of” will be interpreted as equivalent to “comprising” and open to unlisted ingredients that do not materially affect the basic and novel properties of the composition.
Furthermore, Agulnick et al stated that “Applicant explored various cryopreservation conditions to optimize cell survival following cryopreservation” ([0216], page 33) and “It will be apparent to one skilled in the art that varying substitutions, modifications or optimization, or combinations may be made to the embodiments disclosed herein without departing from the scope and spirit of the invention” ([0285], page 43). Agulnick et al teach DMEM containing media comprising different factors and “or others additives as are well known in the art”. Thus, it is a matter of choice to include or exclude DNAse I and anti -apoptotic agents as taught by Agulnick et al. It is well settled that routine optimization is not patentable, even if it results in significant improvements over the prior art. In support of this position, attention is directed to the decision in In re Aller, Lacey, and Haft, 105 USPQ 233 (CCPA 1955). Given that different factors/inhibitors were commercially available and were routinely used in different combination for islet cell medium composition, it would have been prima facie obvious for one of ordinary skill in the art to combine different agents/factors each of which is taught by the prior art to be useful for the same purpose in order to produce a new culture medium that is to be used for the very same purpose. In the instant case the idea of include or exclude them flows logically from there having been taught in the prior art. Further, patentable distinction is not evident between the claimed method and those taught by cited prior art references above before the effective filing date.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KHOA NHAT TRAN whose telephone number is (571)270-0201. The examiner can normally be reached M-F (9-5).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, PETER PARAS can be reached at (571)272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/KHOA NHAT TRAN/Examiner, Art Unit 1632
/PETER PARAS JR/Supervisory Patent Examiner, Art Unit 1632
Prosecution Insights