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 .
DETAILED ACTION
The Applicant’s reply filed on 11/3/25 is acknowledged. Claims 1, 3, 5, 6, 17, 18, 22, 32-34, and 55-65 are pending.
Election/Restrictions
The Restriction Requirement filed 9/3/25 is withdrawn. Upon further consideration, the Examiner agrees that the original election of Compound 101 falls within the scope of claim 1, specifically, as a compound of Formula III-b. The Restriction Requirement filed 9/18/23 is maintained.
Claims 5, 6, 17, 34 and 62-64 are withdrawn. New Claims 63 and 64 are withdrawn as not being directed to Compound 101. Claims 1, 3, 18, 22, 32, 33, 55-61 and 65 are under consideration to the extent that the implantable element comprises the elected species:
(a) a single species of MSFC function from those recited in claim 1: (n) upon introduction, administration, or implantation of the implantable element into a subject a sufficient amount of the polypeptide is produced or released such that an effective concentration of the polypeptide is found in the peripheral bloodstream;
(b) a species of compound of Formula (I) (Compound 101)
(c) a species of polypeptide: insulin
(d) a species of formulation for administration: formulated for implantation into a subject
(e) if the enclosing component is present: yes
(f) and if yes for (e), enclosing component type: a flexible polymer
Withdrawn Rejections
The rejection of Claim 60 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn in view of the amended claim.
Rejections Maintained and New Grounds of Rejections
Information Disclosure Statement
Acknowledgement is made of Applicant’s information disclosure statements (IDS) submitted on 11/3/25. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 3, 18, 22, 32, and 55-61 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites in line 12 “a compound of… Formula (I-b)”. However, the structure shown in line 14 appears to be mislabeled and is actually Formula (I-b-i) as shown on page 71 of the Specification. It is unclear if the claim is limited to the structure shown or to Formula (I-b) which is broader than Formula (I-b-i). Claims 3, 18, 22, 32 and 55-61 are rejected as depending from and not clarifying claim 1.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 32 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 32 recites “wherein the compound of Formulas (I-b), (I-d), or (III-b) is a compound shown in Table 1”. However, Table 1 is not limited to Formulas (I-b), (I-d), or (III-b) and includes structures which are outside of the scope of Claim 1, for example Compounds 103, 104 and 112. Therefore, Claim 32 broadens Claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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, 3, 18, 22, 32, 33, 55-61 and 65 are rejected under 35 U.S.C. 103 as being unpatentable over Anderson et al. (WO 2016/019391; cited in IDS) in view of Weiss (Vitam Horm, 2009; 80: 33-49).
Anderson et al. teach covalently modified alginate polymers (i.e. flexible polymer), possessing enhanced biocompatibility and tailored physiochemical properties, which are useful as a matrix for coating of any material where reduced fibrosis is desired, such as encapsulated cells for transplantation and medical devices implanted or used in the body (e.g. abstract; page 1, lines 11-17).
Anderson et al. teach an implantable element comprising a plurality of engineered mesenchymal stem function cells (MSFCs) (e.g. page 5, lines 11-13, page 105, lines 21-24; Examples) comprising an exogenous nucleic acid which promotes and/or conditions the production of a polypeptide (e.g. page 52-53, lines 30-3; page 106, lines 10-22; page 108, lines 18-end), and the implantable element is modified with a compound of Formula (I):or a pharmaceutically acceptable salt thereof (i.e. derivatives Z1-Y15, Z1-Y19, Z2-Y12) (e.g. page 25). Anderson et al. teach that in some embodiments, the cells are bioengineered to express a recombinant protein, which may be insulin (e.g. comprising an exogenous nucleic acid which promoted the production of insulin, a polypeptide) (e.g. page 45, lines 1-11; page 53, line 29 – page 54, line 2; pages 108-109). As evidenced by Weiss, insulin has both an A- and B-chain (e.g. page 1). Anderson et al. teach that the implantable element is modified with a compound of Formula (I) or a pharmaceutically acceptable salt thereof, which may be that of compound 101 (i.e. Z1-Y15) (e.g. page 25).
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Anderson et al. teach that the results show that encapsulated human cells can achieve glucose responsive, long-term glycemic correction (over 170 days) in an immunocompetent
diabetic animal with no immunosuppression which supports the expectation that human cells encapsulated in the disclosed modified alginates can provide products produced by the encapsulated cells to patients for long periods of time (e.g. Example 9, pages 183-184). This is understood as meeting the limitation, “upon introduction, administration, or implantation of the implantable element into a subject, a sufficient amount of the polypeptide is produced or released such that an effective concentration of the polypeptide is found in the peripheral bloodstream”, because if “an effective concentration of the polypeptide” was not found in the peripheral bloodstream the effect of long-term glycemic correction noted by Anderson would not be achievable.
Regarding Claims 1, 3, 18, 22, 32, 33, 55-59 and 65, while there is not a single example comprising each of the claimed components, the ingredients are included among a short list of preferred ingredients. It would have been obvious to one of ordinary skill in the art at the time of the instant invention to combine the elements as claimed by known methods with no change in their respective functions, and the combination yielding nothing more than predictable results.
Regarding Claim 60, Anderson discloses “[t]he amount and density of cells encapsulated in the disclosed compositions, such as capsules and microcapsules, will vary depending on the choice of cell, hydrogel, and site of implantation. In some embodiments, the single cells are present in the hydrogel at a concentration of 0.1 x106 to 4 x106 cells/ml, preferred 0.5 x106 to 2 x 106 cells/ml” (i.e. at least 10,000, 15,000, or 20,000 cells) (e.g. page 107, lines 21-25).
Regarding Claim 61, Anderson discloses capsules of 150 µm to about 5 cm, including 1-2 mm (e.g. page 78, line 28-page 79, line 3).
Response to Arguments
Applicant's arguments filed 7/7/25 and 11/3/25 have been fully considered but they are not persuasive.
Applicant argues that Anderson is directed to modified alginates with afibrotic properties and their use in preparing generally applicable hydrogel capsules. Anderson is not solely focused on encapsulation of cells and instead teaches modification of various implantable elements such as medical devices, tissues, or macromolecules in addition to cells. In contrast, the instant application is specifically directed to implantable, encapsulated MSFCs rather than afibrotic alginates in the case of Anderson.
This is not found persuasive. It would have been obvious to one of ordinary skill in the art to have selected any of the cell types disclosed by Anderson, including MSFCc. While Anderson discloses more than one option for cell type, “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) (MPEP 2145 D). Anderson et al. teach an implantable element comprising a plurality of engineered mesenchymal stem function cells (MSFCs) (e.g. page 5, lines 11-13, page 105, lines 21-24; Examples) comprising an exogenous nucleic acid which promotes and/or conditions the production of a polypeptide (e.g. page 52-53, lines 30-3; page 106, lines 10-22; page 108, lines 18-end), and the implantable element is modified with a compound of Formula (I):or a pharmaceutically acceptable salt thereof (i.e. derivatives Z1-Y15, Z1-Y19, Z2-Y12) (e.g. page 25). Anderson et al. teach that in some embodiments, the cells are bioengineered to express a recombinant protein, which may be insulin (e.g. comprising an exogenous nucleic acid which promoted the production of insulin, a polypeptide) (e.g. page 45, lines 1-11; page 53, line 29 – page 54, line 2; pages 108-109). The Examiner is not persuaded that the number of potential choices is so great that the conclusion of obviousness is called into question. Merck & Co., Inc. v. Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed. Cir. 1989) ("[D]isclos[ing] a multitude of effective combinations does not render any particular formulation less obvious. This is especially true because the claimed composition is used for the identical purpose taught by the prior art.").
Applicant further argues that Weiss does not disclose implantable elements, afibrotic alginates, mesenchymal stem cells, or the concepts of engineering a mesenchymal stem cell to produce insulin or encapsulating said cell in an implantable device. There is simply no suggestion in Weiss to combine insulin with any of the features of Anderson. A person of ordinary skill in the art would absolutely not think to engineer an MSFC to produce insulin and encapsulate it in an implantable device comprising afibrotic alginates after reading Weiss.
This is not found persuasive. The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). In the instant case Weiss is relied upon simply for evidence that insulin has both an A- and B-chain (e.g. page 1).
Accordingly, the rejection is maintained.
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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NICOLE PLOURDE BABSON whose telephone number is (571)272-3055. The examiner can normally be reached M-Th 8-4:30; F 8-12:30.
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/NICOLE P BABSON/Primary Examiner, Art Unit 1619