FINAL 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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/14/2025 has been considered by the examiner and initialed copies of the IDS are included with the mailing of this office action.
Status of the Claims
This action is in response to papers filed 11/14/2025 in which claims 2-3 were canceled; and claims 6-8 were withdrawn; and claim 1 was amended. All the amendments have been thoroughly reviewed and entered.
Claims 1, 4 and 5 are under examination.
Modified Rejection
Necessitated by Applicant’s Claim Amendments
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.
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.
Claim(s) 1 and 4-5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hillberg et al (Journal of Biomedical Materials Research B: Applied Biomaterial, February 2013, 101B(2): 258-268) in view of Agarwal et al (US 2015/0283287 A1) and Anderson et al (US 2019/0254975 A1).
Regarding claim 1, Hillberg teaches a capsule having a core containing pancreatic islet, wherein the core is an alginate bead containing pancreatic islet, wherein the alginate bead is coated with a layer of polyornithine, and followed by another layer of alginate (Abstract; Introduction; pages 259-260).
While the capsule of Hillberg is not a five-layered membrane, it would have been obvious to modify the capsule of Hillberg to contain additional bilayer coating of polyornithine/alginate around the outermost layer of alginate in view of the guidance from Agarwal.
Agarwal teaches the encapsulation of cells such as pancreatic cells by a multilayer polymer matrix formed by alternating layers of at least one positively charge polyelectrolyte and at least one negatively charge polyelectrolyte, wherein the positively charged polyelectrolyte includes poly(ornithine) and the negatively charge polyelectrolyte include an alginate (Abstract; [0013], [0018], [0058]-[0059], [0140], [0165], [0193], [0201], [0204], [0293], [0296], and [0302]). Agarwal teaches the multilayer polymer matrix can be designed to have at least 4 alternating layers ([0193]). Agarwal teaches the multilayer polymer matrix have excellent mechanical strength ([0106] and [0319]).
It would have been obvious to one of ordinary skill in the art to modify the to modify the capsule of Hillberg to contain additional bilayer coating of polyornithine/alginate around the outermost layer of alginate, and produce the claimed five-layered membrane that cover the core containing pancreatic islet. One of ordinary skill in the art would have been motivated to do so because Agarwal provide the guidance to do so by teaching that the encapsulation of pancreatic cells can tailor to have at least 4 alternating layers of positively charged polyelectrolyte such as polyornithine and negatively charged polyelectrolyte such as alginate, and such resultant multilayer polymer matrix have excellent mechanical strength. One of ordinary skill in the art would have reasonable expectation of success in making said modification to Hillberg because one of the objective of Hillberg is to provide polymeric capsules having excellent mechanical properties (Hillberg: Abstract & Introduction). As such, an ordinary artisan would have looked to modifying the capsule of Hillberg to contain additional bilayer coating of polyornithine/alginate around the outermost layer of alginate so as achieve a desired multilayer capsule with enhanced mechanical strength, and achieve Applicant’s claimed invention with reasonable expectation of success.
However, Hillberg and Agarwal do not teach the formulation has an average diameter of 400 µm or more to 500 µm or less of claim 1.
Regarding the formulation has an average diameter of 400 µm or more to 500 µm or less of claim 1, Anderson teaches encapsulation of pancreas cells such as pancreatic islet using alternating layers of anionic polymer such as alginate and polycationic polymer such as polyornithine (Abstract; [0013]-[0105]). Anderson teaches the encapsulation is in microcapsules having mean diameter of 300 µm to about 750 µm, preferably, about 200 μm to about 500 μm, most preferably from about 400 µm to about 500 µm ([0018]; claim 5).
It would have been obvious to one of ordinary skill in the art to optimize the capsule of Hillberg in view of Agarwal to an average diameter of 400 µm or more to 500 µm or less, and produce the claimed invention. One of ordinary skill in the art would have been motivated to do so because Anderson provided the guidance to do by teaching that capsules for encapsulation of pancreatic cells can be routinely fabricated to have mean diameter of 300 µm to about 750 µm, and most preferably from about 400 µm to about 500 µm, and such mean diameter is suitable for administration to a patient in the treatment of diabetes. It is noted that Hillberg is also using the encapsulated pancreatic islet for the treatment of diabetes (Hillberg: Abstract; Introduction; pages 259-260). Thus, an ordinary artisan would have looked optimizing the capsule of Hillberg in view of Agarwal to mean diameter of from about 400 µm to about 500 µm, a particle size that is suitable for use in the treatment of diabetes, and achieve Applicant’s claimed invention with reasonable expectation of success.
Regarding claim 4, Hillberg teaches the encapsulated pancreatic islet is used for the treatment of diabetes (Abstract; Introduction; page 259).
Regarding claim 5, Hillberg teaches the pancreatic islet was obtained from seven to 10 day old neonatal piglets (page 259, bottom of left column to top of right column).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of Applicant’s invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed 11/14/2025 in have been fully considered but they are not persuasive.
Applicant argues by alleging that “Anderson shows that capsules with a single layer of alginate have a diameter in the range of 400-500 µm and Hillberg shows that three-layered capsules have a diameter of about 700 µm. Based on these teachings, one of ordinary skill in the art would have reasonably expected that capsules having more than three layers of coating would have a diameter much greater than 700 µm, which is above the diameter Anderson identified for effective microcapsule function. Thus, even if one of ordinary skill in the art would have modified the capsule of Hillberg by adding additional bilayer coating to obtain a five-layered capsule as alleged by the Office, which Applicant does not conceive, the skilled person would not have had a reasonable expectation of success that the resulting capsule would have an average diameter smaller than 700 µm, such as 400 µm or more to 500 µm or less as recited in the present claims.” (Remarks, pages 5-6).
In response, the Examiner disagrees. As discussed in the pending 103 rejection, Anderson teaches the encapsulation of pancreas cells such as pancreatic islet using alternating layers of anionic polymer such as alginate and polycationic polymer such as polyornithine (see 103 rejection, page 5 of this office action), particularly paragraph [0067] of Anderson teaches a multi-layer alginate/polylysine-alginate/alginate-cells microcapsule. Thus, contrary to Applicant’s allegation, Anderson does not teach a single layer but rather multi-layer encapsulation of pancreas cells such as pancreatic islet. Thus, given that Anderson is in line with Hillberg with respect to multi-layer microcapsules, it is maintained as discussed in the pending 103 rejection, that it would have been obvious to one of ordinary skill in the art to optimize the capsule of Hillberg in view of Agarwal to an average diameter of 400 µm or more to 500 µm or less because Anderson provided the guidance to do by teaching that capsules for encapsulation of pancreatic cells can be routinely fabricated to have mean diameter of 300 µm to about 750 µm, and most preferably from about 400 µm to about 500 µm, and such mean diameter is suitable for administration to a patient in the treatment of diabetes. It is that the capsule size disclosed in Hillberg (i.e., 700 µm) falls within the optimizable parameter of 300 µm to about 750 µm of Anderson. It is noted that Hillberg is also using the encapsulated pancreatic islet for the treatment of diabetes (Hillberg: Abstract; Introduction; pages 259-260). Thus, an ordinary artisan would have looked optimizing the capsule of Hillberg in view of Agarwal to mean diameter of from about 400 µm to about 500 µm, a particle size that is suitable for use in the treatment of diabetes, and achieve Applicant’s claimed invention with reasonable expectation of success.
As such, contrary to Applicant’s allegation, based on the combined teachings of Hillberg and Anderson, one of ordinary skill in the art would have had reasonable expectation that capsules having more than three layers of coating can be routinely optimize to have mean diameter of from about 400 µm to about 500 µm, a particle size that is suitable for use in the treatment of diabetes, and achieve Applicant’s claimed invention with reasonable expectation of success.
As a result, for at least the reasons discussed above, claims 1, 4 and 5 remain rejected as being obvious and unpatentable over the combined teachings of the cited prior arts in the pending 103 rejection as set forth in this office action.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/DOAN T PHAN/ Primary Examiner, Art Unit 1613