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 .
Status of Claims
Receipt of Arguments/Remarks filed on 5/21/2026 is acknowledged. Claims 1, 5, 8-15, and 17-22 are pending. Claims 1, 5, and 8-9 were amended. Claims 2-4, 6-7, and 16 were canceled. Claims 10-15 and 17-22 are withdrawn as being directed to a non-elected invention.
Priority
The certified copies of the foreign priority documents are not in English. Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
The effective filing date is considered to be 4/5/2021.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 5/21/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
New rejections necessitated by amendment
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, 5, and 8-9 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
In the present instance, claim 1 recites the broad recitation “inflammatory cytokines”, and the claim also recites “including TNF-α having a molecular weight of about 20 kDa” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 1 recites “inflammatory cytokines including TNF-α having a molecular weight of about 20 kDa”. It is not clear if this means that TNF-α specifically has a molecular weight of about 20 kDa, or that the hydrogel structure inhibits diffusion of any inflammatory cytokine that has a molecular weight of about 20 kDa, and TNF-α is an example of such a cytokine.
Claim 1 recites “wherein adjacent layers of three or four pairs of alternating layers hydrogel encapsulation structure are enzymatically crosslinked”. This limitation is unclear. Specifically, it is unclear whether this refers to the pairs of adjacent layers being crosslinked, i.e. the first pair of chitosan/HA being crosslinked to the second pair of chitosan/HA; or if this refers to crosslinking between each individual chitosan and HA layer. Further, the phrasing “alternating layers hydrogel encapsulation structure” is grammatically unclear. It appears that this should instead read “alternating layers of the hydrogel encapsulation structure”. For these reasons, this limitation is unclear. Claim 1 should be amended to clarify these issues.
Claims 5 and 8-9 additionally recite “the three or four alternating layers hydrogel encapsulation structure”, which is unclear as set forth above.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 5, and 8-9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kim et al., Layer-by-layer Cell Coating with Hydrogel Film for Cell Therapy, August 2019, Pages 1-65.
Regarding claim 1, Kim teaches a multilayered hydrogel for cell encapsulation comprising layers of chitosan and hyaluronic acid (Kim p. 12 section 2.1). Kim teaches a hydrogel with 6 layers of chitosan and HA, i.e. three pairs of alternating layers of chitosan and hyaluronic acid (Kim p. 39 first partial para.). The chitosan and HA layers are phenol-functionalized, with 4-Hydroxyphenylacetic acid being used for chitosan and tyramine being used for HA (Kim p. 19 section 2.3.1; p. 21 Fig. 2.2). Kim teaches that the layers are enzymatically crosslinked using Streptomyces avermitilis tyrosinase, or SA-tyr, to form covalent bonds between phenolic functional groups of adjacent layers (Kim p. 12 section 2.1; p. 20 Fig. 2.1). Kim teaches that the thickness of the 6-layer (or 3 pairs of alternating layers) hydrogel is 139.4 nm (Kim p. 39 first partial para.). Kim teaches that β-cell spheroids are encapsulated in the chitosan-HA hydrogel (Kim p. 47 section 3.3.1). Kim teaches that the encapsulation structure is configured to secrete (permit diffusion) of insulin (Kim p. 53 section 3.3.3; p. 55 Fig. 3.6).
Kim teaches the structure of the claimed cell encapsulation multilayered hydrogel: three pairs of alternating layers of phenol-functionalized chitosan (4-Hydroxyphenylacetic acid) and hyaluronic acid (tyramine), wherein the layers are crosslinked by Streptomyces avermitilis tyrosinase to form covalent bonds between layers, and wherein the film has a thickness of 100-200 nm, as set forth above. As understood based on the instant specification, a hydrogel that has these structural features is considered to be configured to selectively permit diffusion of insulin while inhibiting diffusion of inflammatory cytokines. Based on Examples 6 and 8 in the instant specification, it appears that the function of insulin diffusion and inhibited cytokine diffusion is an inherent feature of a hydrogel with the structural features as claimed. It is therefore considered that any hydrogel having this same structure, absent any unclaimed essential features, is capable of performing the claimed function of selective diffusion of insulin while inhibiting diffusion of inflammatory cytokines such as TNF-α. Thus, the hydrogel structure of Kim, which has the same structural features as the claimed hydrogel, anticipates claim 1.
Regarding claims 5, 8, and 9, these claims are directed to functional features of the claimed hydrogel or the cells encapsulated within the hydrogel: the hydrogel encapsulation structure exhibits restricted diffusion of FITC-dextrans while not interfering with insulin secretion (claim 5); the β-cell spheroid exhibits lower expression of p53 and Caspase-3 when treated with TNF-α (claim 8); contact between the β-cell and NK-92 cells is reduced when the encapsulated β-cell spheroid is incubated with NK-92 cells and a spheroid area is maintained over 48 hours (claim 9).
The instant claims are directed to a hydrogel encapsulation structure. Kim teaches the structural features of the hydrogel, as discussed above. Kim further teaches that the hydrogel structure is used to encapsulate β-cell spheroids. It is considered that any hydrogel having this same structure, absent any unclaimed essential features, is capable of performing the claimed function, restricted diffusion of FITC-dextrans. It is further expected that any β-cell encapsulated in such a structure would be capable of the same functional features as claimed: p53 and Caspase-3 expression when treated with TNF-α or contact between NK-92 cells when incubated with NK-92 cells. Thus, the multilayered hydrogel of Kim anticipates claims 5, 8, and 9, as Kim teaches the same structure as set forth in instant claim 1.
Response to Arguments
In light of amendments to the claims, the rejections of claims 1-2, 5, and 9 under 35 U.S.C. § 103 have been withdrawn. However, upon further consideration, new grounds of rejection of claims 1, 5, 8, and 9 are made under 35 U.S.C. § 102 in view of Kim et al. as set forth above. Given these new grounds of rejection, the arguments presented regarding claims rejected under 35 U.S.C. § 103 are moot.
Regarding the Declaration submitted under 37 C.F.R. § 1.132, this declaration refers to teachings of references which are no longer applied, and thus the arguments presented regarding previously applied references are moot. Further, regarding the arguments directed to unexpected results, Kim teaches the structural features of the claimed hydrogel nanofilm, and it is therefore expected that a hydrogel having this structure is capable of performing the recited functions.
Conclusion
Claims 1, 5, and 8-9 are rejected. No claims are 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EMILY F EIX whose telephone number is (571)270-0808. The examiner can normally be reached M-F 8am-5pm ET.
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, Sharmila Landau can be reached at (571)272-0614. 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.
/EMILY F EIX/Examiner, Art Unit 1653
/JENNIFER M.H. TICHY/Primary Examiner, Art Unit 1653
Prosecution Insights