DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant's submission filed on 10/28/2025 has been entered.
Claims 1-8 and 19-21 are pending, all of which have been considered on the merits.
Status of Prior Rejections/Response to Arguments
RE: Rejection of claims 19 and 20 under 35 USC 112(a): The amendment to claim 19 to limit the percentage of mesenchymal stem cells or adipose stem cells which have an insulin expressing cell to at least 69.77% is sufficient to overcome the rejection of record. The data point of 69.77% is supported in the original Fig. 6. The disclosure of the end point (69.77) is sufficient to permit claiming a range of the disclosed end point up to 100% (e.g. at least 69.77% encompasses 69.77%-100%). The rejection is withdrawn.
RE: Rejection of claims 1-5 and 8 under 35 USC 102(a)(1) over Shin et al:
Applicants have amended claim 1 to require that the insulin expressing cells and the mesenchymal stem cells or adipose stem cells are substantially stochastically distributed in relation to each other throughout the cell cluster. Applicants have not provided any explanation as to how these additional words change the BRI of the claim. As was previously stated, there is no definition for ‘stochastically distributed’ in the specification. The ordinary meaning of the word (taken from Merriam-Webster online dictionary) stochastic is 1: random; 2: involving chance or probability. Thus the term “stochastically distributed” is interpreted as “randomly distributed”. Amending the claim to require the cells be substantially [randomly] distributed in relation to each other does not change the BRI of the claim.
Applicants have traversed on the grounds that the heterospheroids shown in Fig. 2c of Shin et al do not satisfy the limitation “wherein the insulin expressing cells and the mesenchymal stem cells or adipose stem cells are substantially stochastically distributed in relation to one another throughout the cell cluster.” Specifically, Applicants assert that the heterospheroids of Shin et al only have 13.85% of MSCs having an IC as a nearest neighbor (citing to information provided in the Gooch Declaration), and this does not satisfy the limitation of ‘substantially stochastically distributed’.
The argument has been fully considered, but is not found persuasive. The issue at hand is the broadest reasonable interpretation (BRI) of the claims, particularly of the BRI of ‘substantially stochastically distributed’. There is no definition for ‘stochastically distributed’ in the specification. The ordinary meaning of the word (taken from Merriam-Webster online dictionary) stochastic is 1: random; 2: involving chance or probability. Thus the term stochastic distribution is a random distribution. From the prosecution record, it has been established that the cell distribution patterns in Fig. 6 are examples of stochastic distribution, but the term ‘stochastic distribution’ is not limited to the exact cell distribution patterns shown in Fig. 6. It is emphasized that at least the images for the Mouse Neo-Islet and Human Neo-Islet (of Fig. 6) do show areas where red ICs are aggregated together and where green ASC/MSC are aggregated together. Thus, ‘stochastic distribution’, as being used in the current application includes distribution patterns where individual cell types are adjacent/aggregated together within a greater cell cluster. The cell distribution pattern shown in Fig. 2c of Shin et al is considered to meet the limitation ‘substantially stochastically distributed’ as, overall, the cells are in a ‘substantially random’ pattern relative to one another. It is appreciated that the MSCs and islets do aggregate within the HS, but the image shown in Fig. 2 C can still be considered ‘substantially random distribution’ of cells, in light of the fact that ‘substantially stochastically distributed’ is being used in the current application to cover distribution patterns where individual cell types are adjacent/aggregated together within a greater cell cluster. Furthermore, the analysis performed by Dr. Gooch supports that there is interspersion of cells (i.e. 13.85% of MSCs are neighbored by an IC). The rejection is therefore maintained.
RE: Rejection of claims 1-8 under 35 USC 103 over Shin et al:
Applicants have traversed the rejection of record on the grounds that Shin et al does not anticipate base claim 1 (for reason set forth above), and Huang et al does not remedy this deficiency.
The argument has been fully considered, but is not found persuasive. For the reasons set forth above the rejection of base claim 1 is maintained. The rejections over dependent claims 2-8 are maintained as proper for the reasons of record.
RE: Rejection of claims 1-8 under [provisional] NSDP of US Patent 11485954, US Patent 12281330 and US Application No: 18/263934:
Applicants did not traverse the rejections.
The rejections are maintained. It is noted US Application No 16/646112 has issued as US Patent 12281330. The rejection has been modified to cite to the US Patent.
New/Maintained Grounds of Rejection
Duplicate Claim Warning
Applicant is advised that should claim 1 be found allowable, claim 21 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). In the instant case, the only difference between claims 1 and 21 is use of the phrases “stochastically distributed” versus “randomly distributed”. There is no definition for ‘stochastically distributed’ in the specification. The ordinary meaning of the word (taken from Merriam-Webster online dictionary) stochastic is 1: random; 2: involving chance or probability. Thus the term stochastic distribution is a random distribution. As such, claims 1 and 21 are claiming the same scope.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-5, 8 and 21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Shin et al., Tissue Eng. Part A 21(5-6): 1024-1035 (2015; published online 01/30/2015), as evidenced by Huang et al., Cell Transplantation 27(7): 1017-1026 (2018).
Shin teaches the formation of heterospheroids containing islet cells and mesenchymal stem cells, which improve the localization of islets with MSCs after transplantation, vascularization in the transplantation region, and antiapoptotic activity of the transplanted islet cells (see entire document, including page 1025, left column, paragraph 1). Dissociated islet cells were mixed with MSCs in ratios of 10:1, 2:1, and 1:1 islet cells:MSCs and cultured in a medium containing FBS using the hanging drop method to form spheroids with the MSCs and islet cells distributed randomly throughout the spheroids (page 1025, Figure 1b; page 1026, left column, paragraph 2; reads on claims 1-3, 5, and 8; the Examiner notes that a substantially random distribution of cells relative to one another in the spheroid, as shown in Figure 2c, constitutes substantial stochastic distribution relative to one another as recited in instant claims 1 and 21). The diameters of the heterospheroids were 78.7±49.7 µm, 100.4±55.7 µm, and 80.6±48.3 µm for islet:MSC ratios of 10:1, 2:1, and 1:1, respectively (page 1027, right column, paragraph 4). The islet cells express insulin (page 1032, Fig. 7; reads on claims 1 and 21).
Huang teaches that human pancreatic islets have diameters of 50-350 µm (see entire document, including page 1018, left column, paragraph 2). As such, the heterospheroids of Shin have diameters that fall within the range of sizes of islets in the human pancreas, thus satisfying the limitations of instant claim 4.
Therefore, claims 1-5, 8 and 21 are anticipated by Shin, as evidenced by Huang, and are rejected under 35 U.S.C. 102(a)(1).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-8 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Shin et al., Tissue Eng. Part A 21(5-6): 1024-1035 (2015; published online 01/30/2015), as evidenced by Huang et al., Cell Transplantation 27(7): 1017-1026 (2018).
As discussed above, claims 1-5, 8 and 21 are anticipated by Shin, as evidenced by Huang. In addition, Shin teaches that heterospheroids are formed by adding 30 µL of a cell suspension at a concentration of 2.7×104 cells/mL to the lid of a Petri dish (page 1026, left column, paragraph 2; the Examiner notes that this cell suspension concentration and volume would result in 810 cells being present in each hanging drop).
However, Shin does not teach the heterospheroid diameter or cell number recited in instant claims 6-7.
While Shin does not teach the heterospheroid diameter or cell number recited in instant claims 6-7, these values would be within the realm of routine optimization from the diameters and cell numbers taught by Shin. Generally, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP § 2144.05 part II A.
It would have been obvious to one of ordinary skill in the art at the time Applicants' invention was made to determine all operable and optimal numbers of cells to include in the heterospheroid for transplant because the number of cells in an islet spheroid is an art-recognized, result-effective variable known to affect the amount of insulin that can be generated by the spheroid which would have been optimized in the pharmaceutical art to provide the desired amount of insulin generation. The Examiner notes that the diameter of the spheroid is a direct result of the number of cells in the spheroid.
Therefore, claims 1-8 and 21 are rendered obvious by Shin, as evidenced by Huang, and are rejected under 35 U.S.C. 103.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-8 and 19-21 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent No. 11485954.
Regarding claims 1-8: Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘954 recite cell clusters that contain particular species of cells from the genus “insulin-producing cells” as recited in the instant claims. As such, the instant claims are ‘anticipated’ by the cited claims of ‘954 and are rejected on the ground of nonstatutory double patenting.
Regarding claims 19-20: Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘954 recite cell clusters that contain particular species of cells from the genus “insulin-producing cells” as recited in the instant claims. Regarding the nearby neighbor distribution: cell clusters wherein at least 69.77% of the nearest neighbors of the MSCs or ASCs are islet cells is considered an obvious variation of the claimed cell clusters of the patent. This conclusion is based on the fact that the Human Neo-Islets illustrated in Fig. 6 of the patent, which are an embodiment within the claim scope, have 69.77% of the nearest neighbors of the MSC/ASCs being insulin expressing cells. It is permissible to look to the specification to determine the scope of the claims for purposes of determine what will be considered an obvious variation of the claims.
Claims 1-8 and 19-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 12281330. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘330 patent are drawn to a method of making a cell cluster that would satisfy the limitations of the instantly recited cell cluster. Therefore, the instant claims are ‘anticipated’ by the cited claims of ‘330 and are rejected on the ground of nonstatutory double patenting.
Claims 1-8 and 19-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 35-53 of copending Application No. 18/263934 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘934 recite a method of making a cell cluster that would satisfy the limitations of the instantly recited cell cluster. Therefore, the instant claims are ‘anticipated’ by the cited claims of ‘934 and are provisionally rejected on the ground of nonstatutory double patenting.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALLISON M FOX whose telephone number is (571)272-2936. The examiner can normally be reached M-F 10-6 EST.
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/ALLISON M FOX/Primary Examiner, Art Unit 1633