Notice of Pre-AIA or AIA Status
The present application, filed on or after 16 Mar 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
Amendments to the claims filed 16 Jul 2026 are acknowledged. Claims 1-9 are withdrawn. Claim 11 is amended. Claims 10 and 13 were previously canceled.
Applicant’s election without traverse to Group III, drawn to claims 11-12, in the reply filed 16 Jul 2026 is acknowledged.
Claims 1-9 and 11-12 are pending. Claims 11-12 are examined on the merits.
Specification
The use of the term Aladdin®, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology, the term should be capitalized wherever it appears, and, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term. Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
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 11-12 are rejected under 35 U.S.C. § 103 as being unpatentable over Gonzalez-Pujana (A. Gonzalez-Pujana, et al. Eur J Pharm Biopharm, 2022) in view of Kim (B.J. Kim, et al. Adv Mater, 2018) and Choi (US 2016/0312175 A1, 2016, cited previously in PTO-892 filed 03 Jun 2026).
Gonzalez-Pujana teaches a method for treating ulcerative colitis (claims 11-12) in which encapsulated mesenchymal stromal cells (MSC, also referred to in the art as mesenchymal stem cells) are administered to mice with acute ulcerative colitis induced by administration of dextran sodium sulfate (DSS) (Abstract, Introduction pp. 31-32, and Materials and Methods § 2.4).
Gonzalez-Pujana further teaches that MSC are commonly delivered by intravenous infusion and that while this approach is regarded as safe and effective for treatment of various diseases, risk of thrombosis (coagulation) is significant (Introduction p. 32). Gonzalez-Pujana further teaches that MSC encapsulation can improve persistence of transplanted cells (Introduction and Materials and Methods § 2.2). Gonzalez-Pujana further teaches that MSC encapsulated in alginate comprising heparin-coated beads are more effective compared to nude MSC in improving stool consistency, inflammation, disease activity index, colon weight: length ratio, histological score, crypt architecture, and epithelium erosion in a mouse DSS model of ulcerative colitis (Results p. 34 and Fig. 2-3).
Gonzalez-Pujana does not teach a method of preparing an anti-coagulant stem cell coating comprising tannic acid, MnCl2·4H2O, and heparin sodium and administering the coating as required by claims 11-12.
However, Kim teaches coating MSC with a metal-polyphenol nanoshell (Abstract and p. 9 § 4.2). Kim further teaches that nanoshell-coated MSC have prolonged survival, protection from sheer stress in the blood stream, enhanced recruitment to injured tissues, and improved efficacy when administered intravenously compared to nude MSC (p. 9 § 4.2). Kim further teaches that such shells are only held intact by metal coordination bonding, which allows for the shells to provides protection but are also degradable, which makes them favorable for cell therapies and allows for cell division (p. 6 § 3.1 and Fig. 5A). Kim further teaches that the metal-polyphenol complex can be formed on virtually any surface, including cells, in a rapid, less than 10 s, single step deposition using a multivalent metal, such as ferric iron) and tannic acid to form a nanoshell coating around a cell, and that this method is favorable over other approaches because of its speed and simple application and because it does not require use of chemicals toxic to the cell (p. 3 § 2.1).
Furthermore, Choi teaches a method for generating a metal-polyphenol coating for mammalian cells comprising tannic acid as the polyphenol and a transition metal salt (Abstract and par. 8 and 46). While Kim teaches using ferric iron as the transition metal, Choi teaches that the choice of transition metal salt for generating metal-polyphenol nanoshells is interchangeable and may be manganese (par. 48). Choi further teaches that the metal may be a salt in the form of a chloride without particular limitation (par. 49). Choi further teaches preparing the coating in aqueous solution, and therefore inherently teaches hydrated MnCl2 (MnCl2·4H2O) (par. 45). Choi further teaches addition of a polyphenol and a transition metal to red blood cells (RBC) with heparin added as an anticoagulant (Example 3 par. 88). The coating is prepared by adding RBC to phosphate buffered saline (PBS) comprising tannic acid and ferric chloride to the RBC solution, incubating for 10 s (mixing evenly to allow incubation to obtain an incubated stem cell solution) followed by washing twice by centrifugation (centrifuging the incubated stem cell solution and collecting a resulting precipitate) to obtain RBC tannic acid-iron-coated nanoshells. Choi further teaches by way of example that the method can be easily applied to multiple cell types, including red blood cells, HeLa cells, a cancer cell line, T lymphocytes, fibroblasts, and yeast (Examples 1-5 par. 76-92).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to improve the method of treating ulcerative colitis by administering encapsulated MSC in a medium comprising heparin as taught by Gonzalez-Pujana by encapsulating the MSC in a metal-polyphenol nanoshell coating comprising ferric iron and tannic acid as taught by Kim and a method of preparing a metal-polyphenol nanoshell coating comprising tannic acid, manganese chloride hydrate, and heparin as taught by Choi to arrive at the claimed invention. One would be motivated to make such a combination as Gonzalez-Pujana teaches that the method of administering MSC for treatment of ulcerative colitis is ready for improvement as MSC delivered intravenously pose a risk of thrombosis and as increased MSC persistence improves efficacy. One would be motivated to use a metal-polyphenol nanoshell coating to make the improvement as Kim teaches that the coating is simple and rapid to prepare, is not cytotoxic, and improves MSC persistence when administered intravenously. One would be motivated to substitute manganese for ferric iron in the coating as Choi teaches that the transition metals are interchangeable. One would be motivated to add heparin to the coating as Gonzalez-Pujana and Choi teach adding heparin as an anticoagulant. One would have a reasonable expectation of success in making the combination as Gonzalez-Pujana teaches that encapsulated MSC have improved efficacy in treating ulcerative colitis, as Kim teaches MSC encapsulated in a metal-polyphenol coating have improved survival and efficacy in a similar disease model.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Eric B Wright whose telephone number is (571) 272-2607. The examiner can normally be reached Mo - Fr, 09:00 a.m. - 05:00 p.m. Eastern. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras can be reached at (571) 272-4517.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant may use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. 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.
Eric B Wright, PhD
Examiner
Art Unit 1632
/Eric B Wright/ Examiner, Art Unit 1632
/VALARIE E BERTOGLIO/Primary Examiner, Art Unit 1632
Prosecution Insights