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 .
Claim Status
Claims 64, 67, 69-73, 75, and 191-206 are currently pending in this application.
Election/Restriction
Applicant’s election without traverse of Group III, claims 64-75, in the reply filed on Jan. 16, 2026 is acknowledged.
Priority
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63/059,563, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for claim 75. Therefore, the earliest effective filing date of claim 75 is the filing date of the instant application, 1/30/2023. If applicant believes the earlier applications provide support for this disclosure, applicant should point out such support with particularity by paragraph and line number in the reply to this Action.
Claim Objections
Claims 64, 67, 69-73, 75, and 191-206 are objected to because of the following informalities: These claims inconsistently use either the term “PDX.1-positive, NKX6.1-positive” cells or “PDX.1-positive, and NKX6.1-positive” cells, which are defined in the instant specification as synonymous ([0097]). Claim 69 as currently amended recites “PDX.1-positive, [[ and ]] NKX6.1-positive” as an underlining denotes added text (see MPEP 714(c)(2)). For clarity and consistency, one of these alternatives should be chosen and used consistently throughout the claims, or should be clearly distinguished for having different meanings, if that is the intent. Appropriate correction is required.
Status of Rejections
Status of the rejections: previous claim rejections under 35 USC §§ 112(a) and 102 are withdrawn in view of the claim amendments.
Claim Interpretation
It is noted that in claims 64, 67, 73, 75 and 191-206, there is no limitation as to any order of the method steps as a matter of grammar or required logic (see MPEP 2111.01(II)), meaning the cells may be contacted with the FGF (and one or more other recited agent) or serum albumin protein in any order or simultaneously for claim 67 and 73, and that the cells may be contacted with the FGF (and one or more other recited agent) or the recited PKC activator in any order or simultaneously for claim 75 and so forth. It is noted that markings such as ‘(a), (b), (c),’ etc. do not automatically denote any claim limitation as to the order of method step performance.
While claim 69 requires a cell population comprising cells that are both PDX.1-positive and NKX6.1-positive, for dependent claims 70-72 the respectively insulin-negative, insulin-positive, or C-peptide positive cells present need not necessarily be PDX.1-positive and/or NKX6.1-positive due to the cell population being open-ended.
In claim 71, the term “insulin-positive” cell is interpreted as meaning a cell that expresses a detectable amount of insulin protein (see [0092]) by any method, and thus, in claim 70, the term “insulin-negative” is interpreted as meaning no detectable insulin protein, such as by methods known in the prior art as of the earliest effective filing date.
In claim 72, the term “C-peptide positive” is interpreted as meaning a cell that expresses a detectable amount of C-peptide by any method.
Claim Rejections - 35 USC § 112(a), New Matter, (new)
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.
Claim 75 is rejected 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. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the invention of claim 75, comprising contacting cells in a population of PDX.1 and NKX6.1-positive cells with one or more of phorbol 12, 13-dibutyrate (PDBU), TPB, phorbol 12-myristate 13-acetate, or bryostatin 1. This lacks support in the application as filed and thus constitutes new matter.
37 CFR 1.118(a) states “No amendment shall introduce new matter into the disclosure of an application after the filing date of the application”. In the instant case, the recitation of the limitation “one or more of phorbol 12, 13-dibutyrate (PDBU), TPB, phorbol 12-myristate 13-acetate, or bryostatin 1” is considered new matter. Upon review of the instant specification, examiner could not find explicit or implicit support for this limitation in the instant filing or in any priority document. Rather, the specification only seems to mention the terms “phorbol 12,” “phorbol 12-myristate” and “13-acetate” at [0317] to specifically recite they are not present (“no exogenous small molecules or signaling pathway agonists or antagonists”). Further, there is no support for all of phorbol 12, 13-dibutyrate (PDBU), TPB, phorbol 12-myristate 13-acetate, and bryostatin 1.
Thus, at the time the application was filed, an Artisan of skill would not recognize from the disclosure that Applicant was in possession of the method of instant claim 75.
MPEP 2163.06 notes “If new matter is added to the claims, the examiner should reject the claims under 35 U.S.C. 112, first paragraph-written description requirement”. In re Rasmussen, 650 F.2d 1212, 211 USPQ 323 (CCPA 1981) teaches that “Whenever the issue arises, the fundamental factual inquiry is whether a claim defines an invention that is clearly conveyed to those skilled in the art at the time the application was filed…If a claim is amended to include subject matter, limitation or terminology not present in the application as filed, involving a departure from, addition to, or deletion from the disclosure of the application as filed, the examiner should conclude that the claimed subject matter is not described in that application.
In claim 75 as currently amended, Applicant appears to be cherry-picking disparate, unconnected, method step parameter species and combinations and/or subcombinations thereof, which are not supported by the originally filed disclosure.
Claim Rejections - 35 USC § 112(b), (modified)
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 69-75 and 201-206 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 69 recites the term “population of PDX.1-positive,[[ and]] NKX6.1-positive cells” which is incoherent and unclear as to what constitutes this cell population. Claims 70-75 and 201-206 are included in this rejection for depending from indefinite claim 69. Further, claims 70-72 each recites the term “cells” of an antecedent population which is ambiguous as to which cells in the population are being referred to as “cells” as the antecedent for “the population” could be PDX.1-positive, NKX6.1-positive cell population in step a) and/or b), and furthermore because b) recites “contacting cells in the population” encompasses contacting only a subset of cells therein, imply some cells in the population are different from others, such as having changed their PDX.1-positive and/or NKX6.1 status, such as being already contacted with one or more other recited agents and cultured for a sufficient duration permitting gene expression changes.
Claim Rejections - 35 USC § 102, (new)
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 64, 67, 69-73, 75, 191-195, 197-204 and 206 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Peterson (US20150218522A1, IDS ref.).
Regarding claim 64, 69, 191-195, 197-204 and 206, Peterson discloses a method of making PDX.1-positive, NKX6.1 positive cells (e.g., insulin+ endocrine or SC-β cells and their progenitors) in a culture medium comprising FGF selected from FGF2, FGF8B, FGF10, and FGF21 ([0007], [0018]-[0019], [0031], [0040]-[0048]) as well as comprising items (i)-(v) and (vii)-(x) recited in claim 64 ([0405]-[00466]):
XXI or DAPT ([0031], [0044], [0294]);
Alk5 inhibitor II, A83-01, SB431542, D4476, GW788388, LY364947, LY580276, GW6604, SB-525334, SD-208, or SB-505124 ([0407]-[0421]);
T3 or GC1 (GC-1) ([0454]);
LDN193189 ([0019], [0046], [0253]);
staurosporine ([0048], [0326], [0339], [0299]);
Sant1, Sant2, Sant4, Cur61414, forskolin, tomatidine, AY9944, triparanol, or a cyclopamine derivative ([0440]);
retinoic acid, CD1530, AM580, TTHPB, CD437, Ch55, BMS961, AC261066, AC55649, AM80, BMS753, tazarotene, adapalene, and CD2314 ([0443]);
EGF and/or betacellulin ([0046], [0048], [0276], [0339]); and/or
Y-27632, Fasudil/HA1077, and H-1152 ([0619], [0068]).
Peterson discloses the contacting the cell population with the FGF and culturing for one day or longer (e.g., 5 days or 7-14 days), such as with medium exchanges/replenishment ([0018], [0046]-[0047]).
Regarding claim 67 and 73, Peterson discloses wherein the cell population is contacted with a serum albumin protein (e.g., 10% fetal bovine serum) ([0007], [0042], [0341], Tables 4-5).
Regarding claims 70-71, Peterson discloses wherein the cell population comprises insulin-negative cells in the form of NKX6-1+ and Pdx1+ pancreatic progenitor cells (insulin+ endocrine or SC-β cells progenitor cells) as well as insulin-expressing cells induced therefrom ([0004]-[0007], [0018]-[0019], [0031], [0040]-[0048], FIG. 2-3, 6, 9-10, 12, 14, and 16).
Regarding claim 72, Peterson discloses wherein the cell population comprises cells expressing C-peptide ([0004], [0007], [0042], FIG. 5-8, 11-13, 15-16).
Regarding claim 75, Peterson discloses including in the culture medium 13-dibutyrate (PdbU), TPB, or bryostatin 1 ([0019], [0046], [0449], [0257]).
Thus, Peterson anticipates claims 64, 67, 69-73, 75, 191-195, 197-204, and 206.
Response to Arguments
Applicant’s remarks filed regarding the previous 102 rejections have been fully considered and found persuasive; however, applicant’s claim amendments resulted in new grounds of rejection laid out above.
Claim Rejections - 35 USC § 103, (new)
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.
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 64, 69, 196, and 205 are rejected under 35 U.S.C. 103 as being unpatentable over Semma (WO2020033879A1).
Regarding claim 64, Semma teaches a method comprising contacting PDX. 1-positive pancreatic progenitor cells in a cell population as follows to induce NKX6.1 expression to produce a PDX.1-positive, NKX6.1 positive cell population ([0253]): with at least one of FGF2 (bFGF), FGF8B, FGF10, and FGF21 for a period of at least five days ([0235]-0239], [0244]), and with one or more of: (i) XXI or DAPT ([0275], [0280]); (ii) Alk5 inhibitor II, A83-01, SB431542, D4476, GW788388, LY364947, LY580276, GW6604, SB-525334, SD-208, and SB-505124 ([0254]-[0255]); (iii) T3 or GC1 (GC-I) ([0255]); (iv) LDN193189 ([0259], [0275]); (v) staurosporine ([0262], [0275]); (vi) DZNep (Deazaneplanocin A hydrochloride) ([0285]); (vii) Sant1 (Sant 1), Sant2, Sant4, Cur61414, forskolin, tomatidine, AY9944, triparanol, or cyclopamine ([0237]-[0238], [0246]-[0248]); (viii) retinoic acid ([0236]-[0237], [0257]); (ix) EGF or betacellulin ([0261], [0275]); and (x) thiazovivin, Y-27632 or Fasudil/HA1077([0237], [0240]-[0248]; [0217], [0236], [0239]).
Regarding claim 196, although Semma does not teach with particularity that FGF8B, FGF10, or FGF21 is necessarily present in the medium with DZNep, Semma teaches adding the histone methylation inhibitor DZNep to aid in gene expression changes, such as in differentiating beta-cells, along with specifically including a keratinocyte growth factor ([0191], [0030], [0046]-[0049]), which includes the “keratinocyte growth factor FGF2” ([0235]).
It would have been prima facie obvious to one of ordinary skill in the art before the earliest effective time of filing to combine into a single medium culturing PDX.1-positive, NKX6.1 positive cell both FGF2 and DZNep to induce pancreatic cell differentiation. One of ordinary skill in the art with the goal of differentiating PDX.1-positive, NKX6.1 positive pancreatic cells from PDX.1-positive progenitor cells would be motived by the teachings of Semma that (1) FGF2 (bFGF) is a "routine" tissue culture component and (2) DZNep for promoting stronger differentiation, e.g., to mature beta-cell.
Regarding claim 69, Semma discloses a method comprising contacting PDX. 1-positive pancreatic progenitor cells in a cell population as follows to induce NKX6.1 expression to produce a PDX.1-positive, NKX6.1 positive cell population ([0253]): with at least one of FGF2 (bFGF), FGF8B, FGF10, and FGF21 for a period of at least five days ([0235], [0244]), and with one or more of: (i) Alk5 inhibitor II, A83-01, SB431542, D4476, GW788388, LY364947, LY580276, GW6604, SB-525334, SD-208, and SB-505124 ([0254]-[0255]); (ii) T3 or GC1 (GC-I) ([0255]); (iii) LDN193189 ([0259], [0275]); (iv) staurosporine ([0262], [0275]); (v) DZNep (Deazaneplanocin A hydrochloride) ([0285]); and (x) thiazovivin, Y-27632 or Fasudil/HA1077([0237], [0240]-[0248]; [0217], [0236], [0239]).
Regarding claim 205, although Semma does not teach with particularity that FGF8B, FGF10, or FGF21 is necessarily present in the medium with DZNep, Semma teaches adding the histone methylation inhibitor DZNep to aid in gene expression changes, such as in differentiating beta-cells, along with specifically including a keratinocyte growth factor ([0191], [0030], [0046]-[0049]), which includes the keratinocyte growth factor FGF2 ([0235]).
It would have been prima facie obvious to one of ordinary skill in the art before the earliest effective time of filing to combine into a single medium culturing PDX.1-positive, NKX6.1 positive cell both FGF2 and DZNep to induce pancreatic cell differentiation. One of ordinary skill in the art with the goal of differentiating PDX.1-positive, NKX6.1 positive pancreatic cells from PDX.1-positive progenitor cells would be motived by the teachings of Semma that (1) FGF2 (bFGF) is a "routine" tissue culture component and (2) DZNep for promoting stronger differentiation, e.g., to mature beta-cell.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERIC J ROGERS whose telephone number is (571)272-8338. The examiner can normally be reached Monday - Friday 9:00-6:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Tracy Vivlemore can be reached on (571) 272-2914. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ERIC J ROGERS/Examiner, Art Unit 1638
/KEVIN K HILL/Primary Examiner, Art Unit 1638
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