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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 01/09/2026 has been entered.
Status of Claims
Amendment filed on 01/09/2026 is acknowledged.
Claim 1 is amended. Claims 1-8 are pending and being examined on the merits herein.
Priority
The instant application, filed on 07/18/2022, is a 371 of PCT/JP2021/001767, filed on
01/20/2021, which claims foreign priority to Japan 2020-011625, filed on 01/28/2020.
Claim Interpretation
Claim 1 language “for transplantation”, and “thereby producing pancreatic islet-containing capsules having a higher glucose responsiveness as compared to pancreatic islet-containing capsules prepared using 8,000 IEQ/mL pancreatic islets” are interpreted as “intended use”, feature or property of the pancreatic islet-containing capsules, because they do not structurally contribute to the method steps.
Claim Rejections - 35 USC § 103
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1 and 3-8 are rejected under 35 U.S.C. 103 as being unpatentable over Williams et al. (WO2014171842, 10/23/2014, IDS of 04/05/2024) in view of Meissner et al. (US20050147595, 06/07/2005, IDS of 04/05/2024) and Villa et al. (Transplantation 2017; 101:125-1035; PTO-892).
Williams teaches methods of making and using an encapsulation system for immunoisolation of living cells of therapeutics, and specifically for use in allo- and xeno- transplantation (Abstract).
Williams discloses in general a method for preparing microencapsulated cells comprising the steps as following: a. incubating living cells in a solution of alginate dissolved in isotonic saline (corresponding to sodium alginate solution A in instant claim 1a) to a concentration of between about 0.5% w/v and 2.5% w/v (overlapping to concentration of 1 w/v% or more to 3 w/v% or less in instant claim 4); b. spraying the cell-containing alginate solution of step a) through an air- or frequency-based droplet generator into a stirring solution of an excess of a cross-linking agent to form one or more gelled cell-containing microcapsules; c. coating the one or more gelled cell-containing microcapsules of step b) with one or more polycations comprising one or more amines; d. contacting the microcapsules with a solution comprising one or more blocking agents capable of providing a blocking group itself capable of covalently binding to an amine; and e. collecting the one or more cell-containing microcapsules to provide the microencapsulated cells (Page 3, Summary of the invention, Lines 14-27; Page 37-38, Claim 42).
Williams further explicitly describes APA (alginate-polyornithine-alginate, as known in the art field) capsule preparation method with details on reagents and concentrations as following: Porcine pancreatic islets were mixed with 1.8% (w/v) alginate (corresponding to preparing a sodium alginate solution A in instant claim 1a) prior to capsule formation and a homogeneous mixture of the two was pumped through a needle supplied with a coaxial airflow (resulting from droplet generator above). Alginate beads were cross-linked in 200 ml of 109 mM CaCl2 for 5 minutes resulting in the formation of encapsulated islets (corresponding to adding the sodium alginate solution A containing pancreatic islets to a divalent cation solution in instant claim 1b). The encapsulated islets were subsequently coated with 0.1 % poly-L-ornithine (PLO) (corresponding to poly-L-ornithine solution A in instant claim 1c; overlapping with poly-L-ornithine solution A concentration of 0.05 w/v% or more to 3 w/v% or less in instant claim 5) for 10 minutes, 0.05% PLO (overlapping to poly-L-ornithine solution B concentration of 0.01 w/v% or more to less than 0.1 w/v% in instant claim 8) for 6 minutes, and 0.18% alginate for 6 minutes (as in general method steps, alginate is dissolved in isotonic saline, corresponding to adding the particles to sodium alginate solution B in instant claim 1d; corresponding to sodium alginate solution B concentration of 0.1 w/v% or more to 0.3 w/v% or less in instant claim 6; corresponding to the particles are added to sodium alginate solution B after being added to a poly-L-ornithine solution B in instant claim 7). After capsule preparation the alginate core was dissolved using 55 mM isotonic sodium citrate (2 minutes) (corresponding to adding the particles to sodium citrate solution in instant claim 1e). The samples were washed with saline solution (0.9 M NaCl) between each step and all solutions were filter sterilized before filtering through a 0.2 μm PES filter (Page 3, Lines 14-27; Page 18, Lines 4-18; Page 22, Lines 9-20; Page 37-38, Claim 42). Since the coating steps are indicated as sequential and the samples are washed with saline solution between each step as disclosed above, stirring the solution to resuspend the islet particles and collecting them after washing are implied default steps to ordinary artisans in the field.
Williams specifically exhibits glucose responsiveness comparisons from APA capsules and AP capsules treated with Sulfo-NHS-acetate in vitro, using parameter ISI (insulin stimulation index) as the ratio of maximum insulin release to low glucose incubation, or maximum release to high glucose incubation (e.g., Table 6-8), concluding APA insulin release values (ISI1, ISI2, MIR) exhibits equivalent (Pg. 29, Tables 6-7) or even higher levels (Table 8, Pg. 30) compared to the Sulfo-NHS-acetate modified AP capsules (Pg. 28, Lines 15-17; Pg. 29, Lines 15-18). Williams states that the modified AP capsules reduces insulin release may being attributed to diffusion of molecule through capsule wall and coating of the islets (Pg. 29, Lines 15-18), indicating APA capsules present advantage in glucose responsiveness when compared to the Sulfo-NHS-acetate modified AP capsules. Glucose responsiveness is the focused feature in instant claim.
For claim 3, The pancreatic islet-containing capsules generated from APA method in Williams have diameters of 743 um, 637 um, and 647 um on 9, 22, 35 batch record days respectively (Page 27, Table 3), 638 um and 641 um on 13 and 35 batch record days (Page 27, Table 4; Page 28, Table 5) (overlapping with capsule diameters of 550 to 750 um in instant claim 3), with additional parameters such as viability, uniformity, and integrity being shown in the analysis using light microscopy (Page 26, Lines 5-8).
Williams does not disclose the concentration of pancreatic islets as 10,000 IEQ/mL or more in the sodium alginate solution A during the preparation as recited in instant claim 1, and does not teach pancreatic islet-containing capsules prepared by using 10,000 or more IEQ/mL shows higher glucose responsiveness than the ones prepared by using 8,000 IEQ/mL pancreatic islets as recited in instant claim 1.
Meissner describes a composition of encapsulated beads formed from alginate comprising pancreatic islets (Abstract, [0002], [0009]). Meissner illustrates the encapsulation of porcine islets in Example 1, indicating that concentrated islets from adventitious excipients were pelleted and washed twice with serum free CMRL media to remove the porcine serum, then the pellet was resuspended in 2% alginate in HEPES buffered saline, PH 7.4, 3003±30 mOsm at a concentration of 10,000-15,000 IE (islet equivalent, IE or IEQ) per mL of final alginate suspension [0065], before proceeding to remaining steps of the method described in detail in the invention. Meissner also specifies in Example 8 [0079] that typical levels around 900-3,000 islets/mL of alginate, leaving as many as 30% of the beads empty (during encapsulation), and in order to reduce the number of empty beads (corresponding to capsules), the loading of islets within the beads is increased to use approximately 10,000-15,000 islet equivalent per mL (IEQ/mL) of alginate suspension. Meissner further points out that the methods of isolating pancreatic islet cells from pigs are known in the art [0063]. The islet concentration taught by Meissner overlaps with that in instant claim 1.
Villa throughout the reference teaches effects of capsule composition and transplantation site on graft outcomes of encapsulated islets in development of effective strategies for islet transplantation without immunosuppression (Abstract).
Villa teaches transplantation of pancreatic islets using fixed-diameter spherical microcapsules such as traditional alginate microcapsule (ALG micro) diameters ranging from 600 to 1000 um, generated with traditional electrostatic droplet generator technology (e.g., Pg. 1025 bottom -Pg. 1026 top left), for transplantation of minimized volumes of encapsulated islets in confined and vascularized sites (Pg. 1026 right top), with final islet loading density of pancreatic islets equal to 5,000, 15,000, and 30,000 IEQ/mL compared to naked islets in determination of encapsulated graft outcomes such as viability (e.g., Pg. 1027, right above Table; Figure 1 C-D), insulin production (Figure 1 E), stimulation indexes (Figure 1F), Villa concludes that the 5,000 IEQ/mL density leads to the highest percentage of cell-free capsules (as disadvantage of causing transplantation volume increase), whereas the 30,000 IEQ/mL density results in multiple islets per capsule (advantage in lowering transplantation volume) (Figure 1C); Live/dead staining and confocal imaging shows that capsules generated with 15,000 IEQ/mL islet density has higher cell viability than capsules with 30,000 IEQ/mL islet density (Figure 1D), and 15,000 IEQ/mL ALG microencapsulated islets have similar GSIR (static glucose-stimulated insulin release index, corresponding to glucose responsiveness in instant claim 1) function as to naked islets (Figures 1E-1F) in addition to homogeneous diameters (median, 525 um; Figure 1G) (Pg. 1026 right bottom-Pg. 1027 left top).
It would have been prima facie obvious for one of ordinary skill in the art prior to the effective filing date of the claimed invention to incorporate the islet concentration taught by Meissner and Villa into the porcine pancreatic islet encapsulation method in Williams to arrive at current invention. Although Williams does not provide a concentration of the islet in the sodium alginate solution, it would have been prima facie obvious for one of ordinary skill in the art to look to the prior art for known concentrations used in a similar manner, such as the concentrations taught in Meissner and Villa. One of ordinary skill in the art would have a reasonable expectation of success as Meissner teaches these concentrations for the same purpose of preparing pancreatic islet encapsulation, especially Villa demonstrates that 15,000 IEQ/mL finds good glucose response and a balance in high viability with islet encapsulation efficiency, which can reduce transplantation volume while remaining glucose responsive efficacy. This renders obviousness as combining prior art elements according to known methods to yield predictable results, see In Supreme Court KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007).
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). MPEP §2144.05(I) states that “A prima facie case of obviousness typically exists when the ranges of a claimed composition overlap the ranges disclosed in the prior art.” See In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003). For this instance, the concentrations of sodium alginate A and B, poly-L-ornithine A and B, concentrations of islets in sodium alginate solution, capsule diameters overlap with those taught by prior art. Furthermore, “[i]t would have been prima facie obvious for one of ordinary skill in the art to optimize additive amount through nothing more than “routine experimentation,” because of a reasonable expectation of success resulting from the optimization for desirable features of intended use of the composition (MPEP §2144.05 (II)). See Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382; In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969). “A prima facie case of obviousness typically exists when the ranges of a claimed composition overlap the ranges disclosed in the prior art.” See In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003).
Regarding of higher glucose responsiveness of using islets in higher concentration than 8,000 IEQ/mL, Williams teaches that the islets generated from APA show equivalent or better glucose responsiveness than modified AP capsules, and Villa demonstrates that higher IEQ/mL, e.g., 15,000 IEQ/mL exhibits not only comparable glucose responsiveness compared to naked in transplantation, but also better viability and effective encapsulation with lower empty capsule rate, further affirming the conclusion of Meissner that lower concentration of islets causes empty encapsulation. For an artisan in the field, reducing empty encapsules would logically generate higher glucose responsiveness in transplantation because there are more valid capsules in function when islet numbers count equally. This would have motivated a person with ordinary skills in the art to incorporate the higher islet concentration in encapsulation preparation for the purpose of transplantation, and it would have provided reasonable expectation of success with such optimization or fine tuning of Williams’ method.
Further, in light of claim interpretation, the phrases in claim 1, “for transplantation”, and “thereby producing pancreatic islet-containing capsules having a higher glucose responsiveness as compared to pancreatic islet-containing capsules prepared using 8,000 IEQ/mL pancreatic islets” are interpreted as “intended use”, feature or property of the pancreatic islet-containing capsules, because they do not structurally contribute to the method steps. Combined teaching of Williams, Meissner and Villa teaches the instantly claimed method of preparing the pancreatic islet-containing capsules with the specified islet concentration, the feature or property of the pancreatic islet-containing capsules would necessarily present in prior art, or the intended use would be capable of being achieved in prior art.
MPEP 2145 II. states that “prima facie obviousness is not rebutted by merely recognizing additional advantages or latent properties present but not recognized in the prior art”, see In re Baxter Travenol Labs., 952 F.2d 388, 21 USPQ2d 1281 (Fed. Cir. 1991) (Appellant argued that the presence of DEHP as the plasticizer in a blood collection bag unexpectedly suppressed hemolysis and therefore rebutted any prima facie showing of obviousness. However, the closest prior art utilizing a DEHP plasticized blood collection bag inherently achieved same result, although this fact was unknown in the prior art.). For this instance, prior art teaches the higher islet concentrations in APA preparation as instantly claimed, therefore, the claimed properties generated from higher islet would necessarily present in prior art, including the higher glucose responsiveness than using 8,000 IEQ/mL islet concentration in APA preparation.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Williams et al. (WO2014171842, 10/23/2014, IDS of 04/05/2024), in view of Meissner et al. (US20050147595, 06/07/2005, IDS of 04/05/2024) and Villa et al. (Transplantation 2017; 101:125-1035; PTO-892), as applied to claims 1 and 3-8 above, and further in view of Elliott et al. (WO 02/32437, 04/25/20222, IDS of 07/18/2022).
The combined teaching of Williams, Meissner and Villa teaches the pancreatic islet encapsulation method with specific islet concentration in alginate solution as discussed above in detail and incorporated herein.
The combined teaching of Williams, Meissner and Villa does not disclose the age of the pig, which is the source of the pancreatic islets.
Elliott teaches a methos of preparing a xenotransplantable porcine islet preparation method comprising (i) harvesting the pancreas of piglets at or near full term gestation, and (ii) extracting islets from a culture of the harvested pancreas using a suitable collagenase, (iii) the culture of the harvested pancreas being a) of mechanically reduced harvested pancreas, and b) a supportive mammalian albumin substantially free of non-human microbiological agents, wherein (at least some stage in the method) the islets are associated with Sertoli cells (Abstract). Elliott exemplifies the effects of collagenase from various sources on islet yield and function, and indicates that pancreases of neonatal piglets aged 7 days are used to extract islets (Page 25, Lines 1-4).
It would have been prima facie obvious for one of ordinary skill in the art prior to the effective filing date of the claimed invention to combine the teaching of Elliott of neonatal piglet age into the porcine pancreatic islet encapsulation method taught by Williams, Meissner and Villa to arrive at current invention. Although the combined teaching of Williams, Meissner and Villa does not provide neonatal piglet age, it would have been prima facie obvious for one of ordinary skill in the art to look to the prior art for known proper islet sources used in a similar manner, such as the one taught in Elliott. One of ordinary skill in the art would have a reasonable expectation of success as Elliott teaches the neonatal piglet age for the same purpose of collecting porcine pancreatic islets for pancreatic islet encapsulation. Combining prior art elements according to known methods to yield predictable results renders obviousness (The Supreme Court in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007), identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham and listed examples of rationale that may support a conclusion of obviousness).
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 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4-9 of copending application 17926082 (hereafter US’082) in view of Williams et al. (WO2014171842, 10/23/2014, IDS of 04/05/2024), Meissner et al. (US20050147595, 06/07/2005, IDS of 04/05/2024) and Villa et al. (Transplantation 2017; 101:125-1035; PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other.
US’082 recites a formulation comprising a core covered with one or more pancreatic islets and other membranes containing alginic acid and poly-L-ornithine, with average diameter of 400 um or more to 500 um or less (Claim 1), and the inner side of second membrane is formed using a 0.075 w/v% poly-L-ornithine solution followed by a 0.038 w/v% poly-L-ornithine solution and the fourth membrane from the inner side is formed using a 0.038 w/v% poly-L-ornithine solution (Claim 9), for use in the treatment of diabetes (Claim 4). US’082 claims the pancreatic islets are obtained from a one- to three-week-old neonatal pig (Claim 5). It recites the method for producing the formulation comprising steps of: (a) preparing a sodium alginate solution A containing one or more pancreatic islets; (b) adding the sodium alginate solution A to a divalent cation solution dropwise, and collecting gelled particles; (c) adding the particles collected in step (b) to a poly-L-ornithine solution A, followed by stirring for a predetermined period of time and then collecting particles; (d) adding the particles collected in step (c) to a sodium alginate solution B, followed by stirring for a predetermined period of time and then collecting particles; (e) adding the particles collected in step (d) to a poly-L-ornithine solution B, followed by stirring for a predetermined period of time and then collecting particles; (f) adding the particles collected in step (e) to a sodium alginate solution C, followed by stirring for a predetermined period of time and then collecting particles; and (g) adding the particles collected in step (f) to a sodium citrate solution, followed by stirring for a predetermined period of time and then collecting particles (Claim 6, corresponding to the method in instant claim 1). US’082 also specifies that the poly-L-ornithine solution A has a poly-L-ornithine concentration of 0.05 w/v% or more to less than 1 w/v% (Claim 7). It further points out that the method according to claim 6 in step (d), the particles collected in step (c) are added to the sodium alginate solution B after being added to a poly-L-ornithine solution A, stirred for a predetermined period of time, and then collected. Though US’082 does not explicitly mention the formulation is for producing pancreatic islet capsules, the preparation method disclosed above along with the membranes coated on the core of pancreatic islets and the obtained islet diameters reveals that the formulation is for pancreatic islet-containing capsules. The poly-L-ornithine concentrations, diameter of islet formulation with membranes (corresponding to islet capsules in instant claims), pig ages overlap or concur with those in instant claims.
US’082 does not recite the pancreatic islet concentration as 10,000 IEQ/mL or more in the alginate solution A during the pancreatic islet-containing capsule preparation, having a higher glucose responsiveness as compared to capsules produced by using pancreatic islet concentration 8,000 IEQ/mL. US’082 also does not recite concentrations of sodium alginate solution A and B.
As discussed above in greater detail, Williams, Meissner and Villa combined teaching provides the encapsulation of porcine islets at a concentration of 10,000-15,000 IE (islet equivalent, IE or IEQ) per mL of final alginate suspension including the concentrations of sodium alginate solution A 1.8% (w/v), poly-L-ornithine solution A 0.1 % (w/v), poly-L-ornithine solution B 0.05% (w/v), and sodium alginate solution B 0.18%, and that glucose responsiveness would be greater than 8,000 IEQ/mL concentration being used in alginate suspension.
It would have been prima facie obvious for one of ordinary skill in the art to incorporate the islet concentration taught by Meissner and Villa and reagent concentrations taught by Williams into the pancreatic islet preparation method recited in US’082 to arrive at current invention. It would have been prima facie obvious for one of ordinary skill in the art to select the known concentrations taught in prior art with a reasonable expectation of success resulting from an intact method of producing porcine pancreatic islet capsules. Selecting a known component to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle. It is not invention. See Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945). Even though the concentrations or diameter values may appear different, it would have been prima facie obvious for one of ordinary skill in the art to optimize amounts through nothing more than “routine experimentation,” to have a reasonable expectation of success resulting from the optimization. Moreover, “A prima facie case of obviousness typically exists when the ranges of a claimed composition overlap the ranges disclosed in the prior art.” See In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003).
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed on 01/09/2026 have been fully considered.
In light of claim amendment and applicant’s remarks, new ground of rejections has been presented above. Prior art reference Villa has been combined with Williams and Meissner to address the amended claim scope.
Since applicant’s arguments are based upon previous rejections in office action mailed on 08/11/2025, in addition to the response in advisory action mailed on 12/23/2025, this office action has updated and set new ground of rejections. Please refer to the entire office action above as a complete response to the arguments.
Regarding some arguments not directly or thoroughly addressed in the office action, they are responded below.
Art Rejections
Applicant asserts that Williams teaching is to improve the biocompatibility of the capsule formulation, while APA capsule is shown as disadvantageous and inferior as a negative control over modified AP capsules, even though Williams shows the results of APA capsules are equivalent to the improved capsules (Williams Tables 3-7), Williams teaches away from using APA capsules as the basis for further improvement.
As MPEP 2145.D.I states "[a] prior art reference that "teaches away" from the
claimed invention is a significant factor to be considered in determining obviousness. However, "the nature of the teaching is highly relevant and must be weighed in substance. A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use." In re Gurley, 27 F.3d 551, 553, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994)"; Furthermore, "the prior art's mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed .... " In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir.2004). See also UCB, Inc. v. Actavis Labs, UT, Inc., 65 F.4th 679, 692, 2023 USPQ2d 448 (Fed. Cir. 2023)".
The "disadvantage" as applicant alleged in Williams teaching of APA capsule does not lead to prior art "teaches away", and does not make the obvious composition patentable simply because APA capsule has somewhat inferior to AP capsule. Moreover, claim scope being set for successful pancreatic islet-containing capsule preparation, and intended use for transplantation and for having glucose responsiveness compared to lower islet, e.g., 8,000 IEQ/mL in alginate solution during the preparation, not the same as Williams’s purpose of improving biocompatibility. For the pancreatic islet-containing capsule preparation as the instant claimed purpose, islet viability and integrity demonstrates advantage of APA capsules over AP capsules, as Williams provides evidence in Tables 3-7. It is worth noticing that Williams does not indicate the control as a negative control -rather as a standard islet preparation method as reference control, and does not indicate APA capsules as inferior, on the contrary, Williams shows study results of APA capsules are comparable to the modified capsules/methods in viability of encapsulated porcine pancreatic islets, size, uniformity and integrity, and capsule counts containing islets; more importantly, APA has slightly better viability than modified at BR day 9 (Table 3), APA has the best viability at BR day 35 (Table 4), and the best viability at day 13 and 35, as well as best integrity along with the highest level of containing islets (Table 5); the most importantly, as presented in office action above and copied below for reference, Williams concludes that the modified methods/ AP capsules even negatively impact insulin release, which is obviously disadvantageous regarding glucose responsive (Tables 6-7, Pg. 28-29), as copied below the relevant paragraph from the office action for reference:
Williams specifically exhibits glucose responsiveness comparisons from APA capsules and AP capsules treated with Sulfo-NHS-acetate in vitro, using parameter ISI (insulin stimulation index) as the ratio of maximum insulin release to low glucose incubation, or maximum release to high glucose incubation (e.g., Table 6-8), concluding APA insulin release values (ISI1, ISI2, MIR) exhibits equivalent (Pg. 29, Tables 6-7) or even higher levels (Table 8, Pg. 30) compared to the Sulfo-NHS-acetate modified AP capsules (Pg. 28, Lines 15-17; Pg. 29, Lines 15-18). Williams states that the modified AP capsules reduces insulin release may being attributed to diffusion of molecule through capsule wall and coating of the islets (Pg. 29, Lines 15-18), indicating APA capsules present advantage in glucose responsiveness when compared to the Sulfo-NHS-acetate modified AP capsules. Glucose responsiveness is the focused feature in instant claim.
The advanced features that APA capsules provide as presented above would have motivated artisans to choose APA method from Williams to produce APA capsules. In addition to Williams, Meissner and Villa further provide motivation for using more than 8,000 IEQ/mL islets for limiting emptiness of capsules, as a result, suitable for transplantation having higher glucose responsiveness, see the paragraph copied from office action below:
Regarding of higher glucose responsiveness of using islets in higher concentration than 8,000 IEQ/mL, Williams teaches that the islets generated from APA show equivalent or better glucose responsiveness than modified AP capsules, and Villa demonstrates that higher IEQ/mL, e.g., 15,000 IEQ/mL exhibits not only comparable glucose responsiveness compared to naked in transplantation, but also better viability and effective encapsulation with lower empty capsule rate, further affirming the conclusion of Meissner that lower concentration of islets causes empty encapsulation. For an artisan in the field, reducing empty encapsules would logically generate higher glucose responsiveness in transplantation because there are more valid capsules in function when islet numbers count equally. This would have motivated a person with ordinary skills in the art to incorporate the higher islet concentration in encapsulation preparation for the purpose of transplantation, and it would have provided reasonable expectation of success with such optimization or fine tuning of Williams’ method.
Applicant asserts that Williams AP capsule preparation method does not include a step corresponding to step (d) of claim 1, therefore, prior art does not teach the claimed method.
The office action presents above the general capsule preparation and APA capsule preparation methods in Williams as the teaching of the instant method, not the specific AP capsule preparation method as applicant referred to.
Applicant alleges that prior art, e.g., Williams and Meissner, would have been workable to have higher concentration of islet from Meissner in the method of Williams, for just having the same purpose of preparing pancreatic islet encapsulated beads or capsules, while lacking reasonable expectation of success by modifying general islet concentration of about 3,000 islets per mL.
In response, arguments presented by the applicant cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965). Williams does not indicate that islet concentration has to be about 3,000 islets. Williams does not exclude higher islet concentration. There is no evidence in Williams that higher islet concentrations would not work. Objective evidence which must be factually supported by an appropriate affidavit or declaration to be of probative value includes evidence of unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the inventor or at least one joint inventor. See, for example, In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984). Furthermore, Meissner and Villa both show advantages of using higher than 8,000 IEQ/mL islet concentrations, and prior art points out that APA method is well known in the field of art, which means incorporating the higher islet concentration into the method is not only workable, but also advantageous as they demonstrate.
In conclusion, Williams, Meissner, and Villa combined teaching teaches the current invention.
Nonstatutory Double Patenting Rejection
Applicant requests provisional nonstatutory double patenting rejection to be held.
A request to hold a rejection in abeyance is not a proper response to a rejection. Rather, a request to hold a matter in abeyance may only be made in response to an OBJECTION or REQUIREMENTS AS TO FORM (see MPEP §714.02 and 37 CFR 1.111(b)). Thus, the double patenting rejection(s) of record has/have been maintained as no action regarding these rejections has been taken by Applicants at this time.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DONGXIU ZHANG SPIERING whose telephone number is (703)756-4796. The examiner can normally be reached 7:30am-5:00pm (Except for Fridays).
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, SUE X. LIU can be reached at (571)272-5539. 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.
/DX.Z./ Examiner, Art Unit 1616
/SUE X LIU/ Supervisory Patent Examiner, Art Unit 1616
Prosecution Insights