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
This action is in response to the papers filed February 12, 2026.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 02/12/2026 has been entered.
Claim Amendments
Applicant’s amendment to the claims filed 02/12/2026 is acknowledged.
Claims 2, 5-8, 11-14 have been cancelled.
Claims 1, 3 and 9 are amended.
Claim 15 is newly added.
Claims 1, 3-4, 9-10 and 15 are pending.
Claims 1, 3-4, 9-10 and 15 are under examination.
Election/Restrictions
The following is a summary of the restriction/election requirements in the application. See Requirement for Restriction/Election mailed 11/13/2023.
In the reply filed 01/05/2024, applicant elected without traverse:
Invention I, directed to a method of enriching for pancreatic endocrine cells expressing NKX6.1 and insulin; and
a ligand that binds to CD26, as the species of ligand that binds to a negative cell surface marker.
As explained in the prior Office action mailed 08/15/2024, claim 3, previously withdrawn from consideration pursuant to 37 CFR 1.142(b) as being directed to a non-elected species, has been rejoined in view of applicant’s amendment to the claims filed 05/29/2024. In this case, claim 3 has been amended to recite that selection from the Markush grouping of negative cell surface markers is optional, and, therefore, amended claim 3 broadly embraces applicant’s elected species of CD26.
As explained in the prior Office action mailed 08/15/2024, the non-elected species of a ligand binding to CD340, as the ligand that binds to a negative cell surface marker, has been rejoined. A ligand binding to CD340 is claimed as an optional feature of claim 3.
Priority
The instant application 18/137,455 was filed on 04/21/2023. This application is a continuation (CON) of U.S. Application No. 15/780,153 filed 05/30/2018 (now, U.S. Patent No. 11,679,133 B2); claiming priority based on international application PCT/IL2016/051274 filed 11/28/2016; U.S. Provisional Application No. 62/366,651 filed 07/26/2016; and U.S. Provisional Application No. 62/260,669 filed 11/30/2015.
Terminal Disclaimer
As discussed in the prior Office action mailed 08/15/2024, the terminal disclaimer filed on 05/29/2024 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of U.S. Patent No. 11,679,133 B2 has been reviewed and accepted.
Withdrawal of Prior Rejections/Objections
Rejections and/or objections not reiterated from the previous Office action mailed
08/14/2025 are hereby withdrawn. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application. In particular, the previous claim rejections under 35 U.S.C. 103, relying on Kelly (US 2013/0122520 A1) and Rezania (US 2015/0329828 A1), have been withdrawn for the following reasons:
The declaration of Micheal Walker under 37 CFR 1.132, filed on 02/12/2026, is acknowledged. Micheal Walker is a co-inventor of the present application. The declarant concludes that the cell surface expression of the CD49a protein is undetectable in naturally occurring human beta cells. The declaration cites the publication of Sharivkin et al. (2015) “Functional proteomics screen enables enrichment of distinct cell types from human pancreatic islets” PLoS One, 10(2), e0115100, 13 pages. For completeness of the record, a paper copy and PTO-892 citation of the publication have been provided with this Office action.
Applicant’s remarks filed on 02/12/2026, and the traversal of the previous claim rejections under 35 U.S.C. 103, are also acknowledged. Applicant argues that Kelly’s Stage 5 cells expressing CD49a are structurally-distinct from Rezania’s Stage 7 cells co-expressing MAFA, NKX6.1 and insulin, which uses an AXL inhibitor to induce maturation into said MAFA+NKX6.1+INS+ pancreatic endocrine cells. Therefore, the expression of CD49a on the surface of Stage 7 cells co-expressing MAFA, NKX6.1 and insulin would have been unknown and unpredictable. Applicant concludes the inventors were the first to demonstrate that CD49a is expressed on the surface of Stage 7 cells co-expressing MAFA, NKX6.1 and insulin, and such a finding would have been unexpected because naturally-occurring mature human β cell do not express CD49a at detectable levels.
Allowable Subject Matter
Claim 15 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and in independent form by including all of the limitations of the base claim and any intervening claims.
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.
Claim 15 is 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.
The term “beta cell-like” in claim 15 is a relative term which renders the claim indefinite. The term “beta cell-like” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. For example, it is unclear what standard or minimally-sufficient characteristics are required by applicant to categorize a cell as “like” a beta cell, or what characteristics would necessarily categorize a cell as “unlike” a beta cell. The specification further does not provide a definition for the term, nor does the specification describe what cell phenotypes are “beta cell-like” cell phenotypes. For these reasons, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention as claimed.
Amending claim 15 by deleting the phrase “of a beta cell-like population” would be remedial. Moreover, claim 15 would be allowable if the examiner’s suggestion were to be adopted and the claim rewritten in independent form to include all of the limitations of claim 1.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 3-4, 9-10 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
This is a scope of enablement rejection.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The factors listed below have been considered in the analysis of enablement:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Claim 15 recites a process of enriching NKX6.1+MAFA+INS+ pancreatic endocrine cells from a cell population by selecting for surface expression of CD49a. The NKX6.1+MAFA+INS+ pancreatic endocrine cells may be obtained from any source or process, broadly including pancreatic endocrine cells induced from any ex vivo differentiation protocol and naturally-occurring pancreatic endocrine cells isolated from the body.
The working examples in the specification describe CD49a-enrichment of NKX6.1+MAFA+INS+ pancreatic endocrine cells derived from Stage 7 of a particular differentiation protocol comprising a series of culturing steps, each step requiring a specific combination of biologically-active agents to drive cell specification towards the target cell type and away from alternative cell fates. See, e.g., Examples 1 and 7 on pages 31-32 and 39-43 of the specification. The specification does not describe CD49a-enrichment of NKX6.1+MAFA+INS+ pancreatic endocrine cells derived from any other ex vivo differentiation protocol, nor the enrichment of naturally-occurring mature β cells by CD49a selection. Accordingly, the working examples are not commensurate in scope with the present claims.
The declaration of Micheal Walker under 37 CFR 1.132, filed on 02/12/2026, concludes that the cell surface expression of CD49a is undetectable in naturally-occurring human beta cells. Accordingly, applying the claimed process to naturally-occurring mature β cells would not have been enabled based on the evidence of record. Further, in remarks filed on 02/12/2026, applicant argues that Stage 5 pancreatic endocrine cells derived from Kelly’s differentiation protocol (US 2013/0122520 A1) are structurally-distinct from the Stage 7 pancreatic endocrine cells derived from Rezania’s differentiation protocol (US 2015/0329828 A1) and that of the present application (Examples 1 and 7), which uses an AXL inhibitor to induce maturation into said MAFA+NKX6.1+INS+ pancreatic endocrine cells. Accordingly, the expression of CD49a on the surface of pancreatic endocrine cells, derived from any other ex vivo differentiation protocol or from nature, would have been unpredictable at the time of the invention.
The teachings of the instant specification do not resolve the unpredictability in the art of enriching mature pancreatic endocrine cells from any heterologous cell population by selecting for surface expression of CD49a that is commensurate in scope with the present claims, and considering the lack of teachings or guidance provided by the specification to overcome the art-recognized unpredictability, and for the specific reasons cited above, it would have required undue experimentation for one of skill in the art to practice the claimed invention. Dependent claims 3-4, 9-10 are included in the basis of the rejection because they do not correct the deficiencies of the claim upon which they depend.
Claim 15 is not included in the basis of this rejection because the claim corrects the deficiencies of the claim upon which it depends.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAMES J GRABER whose telephone number is (571)270-3988. The examiner can normally be reached Monday-Thursday: 9:00 am - 4:00 pm.
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, James D Schultz can be reached on (571)272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JAMES JOSEPH GRABER/Examiner, Art Unit 1631
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