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
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.
Election/Restrictions
Applicant’s election without traverse of Invention I, claims 1-8, 11-21, 25-27, 32-34, 38-39, and 43-47, in the reply filed on Mar. 18, 2026 is acknowledged. Applicant’s election without traverse of the species of PDX1-positive cells, NKK6.1 positive cells as recited in claims 14 and 118 without traverse is acknowledged.
Claims 1-8, 11-21, 25-27, 32-34, 38-39, 43-47 and 144 remain pending in the current application, claims 20, 21, 25, 32-34, 38-39, 43-45, and 144 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention or species.
Based on the results of the search, the species election requirement between the species of Groups a, b, d, e and f has been withdrawn. The species election between these Groups (a, b, d, e and f) and Group c is maintained.
The requirement for the restriction of Inventions I-VI is still deemed proper and is therefore made FINAL.
Claims 1-8, 11-19, 26-27, 32-34, 38-39, and 43-47 have been considered on the merits.
Status of the Claims
Claims 1-8, 11-21, 25-27, 32-34, 38-39, 43-47 and 144 are currently pending.
Claims 25 and 32 are amended.
Claims 20, 21, 25, and 144 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species or Invention, there being no allowable generic or linking claim.
Claims 9-10, 22-24, 28-31, 35-37, 40-42, 48-143 and 145 are cancelled.
Claims 1-8, 11-19, 26-27, 32-34, 38-39, and 43-47 have been considered on the merits.
Specification
The disclosure is objected to because of the following informalities: the use of trademarks.
The use of the term Gibco Synth-a-Freeze™ in 0245, 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; furthermore the term should be capitalized wherever it appear or, 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.
Appropriate correction is required.
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 5 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 5 recites the broad recitation “about 0.005% to about 0.5% (w/v)”, and the claim also recites “about 0.01% to about 0.2% (w/v), about 0.02% to about 0.1% (w/v), or about 0.03% to about 0.08% (w/v)” which are the narrower embodiments of the range. The claim is 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.
Appropriate correction is required.
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, 8, 13-16, 26, 27, 32-34, 38, 39, and 43-47 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Vallier et al. (US 2015/0225698 A1).
With respect to claims 1, 3 and 4, Vallier teaches an in vitro composition containing a plurality of pancreatic β cells or precursor cells and a culture medium containing polyvinyl alcohol (CDM-PVA) (0008-0014 and 0042). With respect to claim 5, Vallier teaches 1 mg/ml of PVA (polyvinyl alcohol) or 0.1% w/v (0042).
With respect to claims 2, 8 and 14, Vallier teaches the pancreatic β cells express insulin and NKX6.1, the pancreatic β precursor cells express NKX6.1 and PDX1 and that INS (insulin), PDX1, are NKX6.1 are pancreatic markers (Fig. 1, 0108, 0116, 0162 and 0217).
With respect to claims 13, 15 and 16, Vallier teaches a stage 1 medium containing Activin-A and bFGF; a stage 2 medium containing SB-431542, FGF10, all-trans retinoic acid and Noggin; a stage 3 medium containing FGF10, all-trans retinoic acid, KAAD-cyclopamine and Noggin; a stage 4 medium containing FGF10; and maturation medium containing B27™ and DAPT (0201).
With respect to claim 26, Vallier teaches the composition where the pancreatic β precursor cells are FOXA2-positive primitive foregut cells (0099). With respect to claim 27, Vallier teaches the composition where the FOXA2-positive primitive foregut cells are in a medium containing the second or third pancreatic induction medium (stage 2 or stage 3) medium. Stage 2 contains SB-431542 (TGF-β singling pathway inhibitor), FGF10, all-trans retinoic acid (retinoic acid signaling pathway activator) and Noggin and stage 3 contains FGF10, all-trans retinoic acid, KAAD-cyclopamine and Noggin (0201).
With respect to claim 32, Vallier teaches the composition where the pancreatic β precursor cells are SOX17-positive definitive endoderm cells (Fig. 1 and 0010-0011). With respect to claims 33 and 34, Vallier teaches the composition where the SOX17-positive definitive endoderm cells are in a medium containing the stage 1 or stage 2 medium (Fig. 1). Stage 1 medium contains Activin-A and bFGF and stage 2 contains SB-431542, FGF10, all-trans retinoic acid and Noggin (0010-0011 and 0201).
With respect to claims 38 and 44, Vallier teaches the composition where the pancreatic β precursor cells are pluripotent stem cells (Fig. 1, 0007, 0009). With respect to claim 39, Vallier teaches the composition where the pluripotent stem cells are in a definitive induction medium containing TGF-β, FGF, BMP, a PI3K inhibitor, BMP and optionally a GSK3 β inhibitor (0009-0010). With respect to claim 43, Vallier teaches the composition containing SOX17-positive definitive endoderm cells which would include pluripotent stem cells as they differentiate (Fig. 1 and 0093). With respect to claim 44, Vallier teaches the composition where the pancreatic β precursor cells are human pluripotent stem cells (Fig. 1 and 0018). With respect to claim 45, Vallier teaches the composition where the pluripotent stem cells are embryonic stem cells or induced pluripotent stem cells (0020).
With respect to claims 46 and 47, Vallier teaches the culture medium not containing any albumin (0040).
Therefore, the reference anticipates the claimed subject matter.
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.
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 1-8, 13-18, 26, 27, 32-34, 38, 39, and 43-47 are rejected under 35 U.S.C. 103 as being unpatentable over Vallier et al. (US 2015/0225698 A1) as evidenced and in view of Kuriyama et al. (US 2017/0009200 A1).
With respect to claims 1, 3 and 4, Vallier teaches an in vitro composition containing a plurality of pancreatic β cells or precursor cells and a culture medium containing polyvinyl alcohol (CDM-PVA) (0008-0014 and 0042). With respect to claim 5, Vallier teaches 1 mg/ml of PVA (polyvinyl alcohol) or 0.1% w/v (0042).
With respect to claims 2, 8 and 14, Vallier teaches the pancreatic β cells express insulin and NKX6.1, the pancreatic β precursor cells express NKX6.1 and PDX1 and that INS (insulin), PDX1, are NKX6.1 are pancreatic markers (Fig. 1, 0108, 0116, 0162 and 0217).
With respect to claims 13, 15 and 16, Vallier teaches a stage 1 medium containing Activin-A and bFGF; a stage 2 medium containing SB-431542, FGF10, all-trans retinoic acid and Noggin; a stage 3 medium containing FGF10, all-trans retinoic acid, KAAD-cyclopamine and Noggin; a stage 4 medium containing FGF10; and maturation medium containing B27™ and DAPT (0201).
With respect to claim 26, Vallier teaches the composition where the pancreatic β precursor cells are FOXA2-positive primitive foregut cells (0099). With respect to claim 27, Vallier teaches the composition where the FOXA2-positive primitive foregut cells are in a medium containing the second or third pancreatic induction medium (stage 2 or stage 3) medium. Stage 2 contains SB-431542 (TGF-β singling pathway inhibitor), FGF10, all-trans retinoic acid (retinoic acid signaling pathway activator) and Noggin and stage 3 contains FGF10, all-trans retinoic acid, KAAD-cyclopamine and Noggin (0201).
With respect to claim 32, Vallier teaches the composition where the pancreatic β precursor cells are SOX17-positive definitive endoderm cells (Fig. 1 and 0010-0011). With respect to claims 33 and 34, Vallier teaches the composition where the SOX17-positive definitive endoderm cells are in a medium containing the stage 1 or stage 2 medium (Fig. 1). Stage 1 medium contains Activin-A and bFGF and stage 2 contains SB-431542, FGF10, all-trans retinoic acid and Noggin (0010-0011 and 0201).
With respect to claims 38 and 44, Vallier teaches the composition where the pancreatic β precursor cells are pluripotent stem cells (Fig. 1, 0007, 0009). With respect to claim 39, Vallier teaches the composition where the pluripotent stem cells are in a definitive induction medium containing TGF-β, FGF, BMP, a PI3K inhibitor, BMP and optionally a GSK3 β inhibitor (0009-0010). With respect to claim 43, Vallier teaches the composition containing SOX17-positive definitive endoderm cells which would include pluripotent stem cells as they differentiate (Fig. 1 and 0093). With respect to claim 44, Vallier teaches the composition where the pancreatic β precursor cells are human pluripotent stem cells (Fig. 1 and 0018). With respect to claim 45, Vallier teaches the composition where the pluripotent stem cells are embryonic stem cells or induced pluripotent stem cells (0020).
With respect to claims 46 and 47, Vallier teaches the culture medium not containing any albumin (0040).
Vallier does not teach the composition where the water-soluble polymer is at a concentration of about 0.04-0.06% w/v in the culture medium as recited in claim 6 or at a concentration of about 0.05% w/v in the culture medium as recited in claim 7. However, one of ordinary skill in the art would recognize that the concentration of the water-soluble polymer in the culture medium is a result effective variable and that the concentration of the water-soluble polymer would be matter of routine optimization as evidenced by Kuriyama. Kuriyama teaches a cell culture medium for stem cells containing a water-soluble polymer which can be polyvinyl alcohol as a substitute for albumin (0009, 0015, and 0023). Kuriyama teaches that the amount of a medium additive, water-soluble polymer, that is added to the basal medium is determined depending on desired effect and the kind of water-soluble polymer added (0067). Kuriyama further teaches that when the concentration of the water-soluble polymer is too low there may be affect and when it is too high it might cytotoxic (0062). Generally, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation" In re Aller, 220 F.2d 454,456, 105 USPQ 233,235 (CCPA 1955) -MPEP § 2144.05.
Vallier is silent with respect to the percentage of hydrolyzed PVA and does not teach the composition where the PVA is more than 85% hydrolyzed as recited in claim 17 or where the PVA is about 87-89% hydrolyzed as recited in claim 18.
However, Kuriyama teaches a cell culture medium for stem cells containing a water-soluble polymer which can be polyvinyl alcohol as a substitute for albumin (0009, 0015, and 0023). Kuriyama further teaches PVA with hydrolysis ratio of 88% and a hydrolysis ratio of 86.5-89% (0077, 0080 and 0082). Kuriyama teaches the PVA with a hydrolysis of 75-90% and when the hydrolysis ratio is too low, water-solubility is not sufficient and, when it is too high, hydroxyl groups of polymers form a hydrogen bond to lower the solubility and dispersibility in water.
Accordingly, at the effective time of filing of the claimed invention one of ordinary skill in the art would have been motivated to modify the cell culture medium of Vallier so that the PVA included has a percentage of hydrolyzed PVA that is greater than 85% and/or between 87-89%, for the benefit of effectively culturing the cells as taught by Kuriyama. It would have been obvious to one of ordinary skill in the art to use PVA with these percentages of hydrolysis, since these percentages were known in the art to culture cells in medium without albumin as taught by Kuriyama. Additionally, one of ordinary skill in the art would have had a reasonable expectation of success in making such a modification to Vallier, since these were known percentages for cell culture as taught by Kuriyama.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claims 1-8, 11-16, 19, 26, 27, 32-34, 38, 39, and 43-47 are rejected under 35 U.S.C. 103 as being unpatentable over Vallier et al. (US 2015/0225698 A1) as evidenced by Kuriyama et al. (US 2017/0009200 A1) and in view of Harb et al. (US 2022/0090020 A1) (ref. of record).
With respect to claims 1, 3 and 4, Vallier teaches an in vitro composition containing a plurality of pancreatic β cells or precursor cells and a culture medium containing polyvinyl alcohol (CDM-PVA) (0008-0014 and 0042). With respect to claim 5, Vallier teaches 1 mg/ml of PVA (polyvinyl alcohol) or 0.1% w/v (0042).
With respect to claims 2, 8 and 14, Vallier teaches the pancreatic β cells express insulin and NKX6.1, the pancreatic β precursor cells express NKX6.1 and PDX1 and that INS (insulin), PDX1, are NKX6.1 are pancreatic markers (Fig. 1, 0108, 0116, 0162 and 0217).
With respect to claims 13, 15 and 16, Vallier teaches a stage 1 medium containing Activin-A and bFGF; a stage 2 medium containing SB-431542, FGF10, all-trans retinoic acid and Noggin; a stage 3 medium containing FGF10, all-trans retinoic acid, KAAD-cyclopamine and Noggin; a stage 4 medium containing FGF10; and maturation medium containing B27™ and DAPT (0201).
With respect to claim 26, Vallier teaches the composition where the pancreatic β precursor cells are FOXA2-positive primitive foregut cells (0099). With respect to claim 27, Vallier teaches the composition where the FOXA2-positive primitive foregut cells are in a medium containing the second or third pancreatic induction medium (stage 2 or stage 3) medium. Stage 2 contains SB-431542 (TGF-β singling pathway inhibitor), FGF10, all-trans retinoic acid (retinoic acid signaling pathway activator) and Noggin and stage 3 contains FGF10, all-trans retinoic acid, KAAD-cyclopamine and Noggin (0201).
With respect to claim 32, Vallier teaches the composition where the pancreatic β precursor cells are SOX17-positive definitive endoderm cells (Fig. 1 and 0010-0011). With respect to claims 33 and 34, Vallier teaches the composition where the SOX17-positive definitive endoderm cells are in a medium containing the stage 1 or stage 2 medium (Fig. 1). Stage 1 medium contains Activin-A and bFGF and stage 2 contains SB-431542, FGF10, all-trans retinoic acid and Noggin (0010-0011 and 0201).
With respect to claims 38 and 44, Vallier teaches the composition where the pancreatic β precursor cells are pluripotent stem cells (Fig. 1, 0007, 0009). With respect to claim 39, Vallier teaches the composition where the pluripotent stem cells are in a definitive induction medium containing TGF-β, FGF, BMP, a PI3K inhibitor, BMP and optionally a GSK3 β inhibitor (0009-0010). With respect to claim 43, Vallier teaches the composition containing SOX17-positive definitive endoderm cells which would include pluripotent stem cells as they differentiate (Fig. 1 and 0093). With respect to claim 44, Vallier teaches the composition where the pancreatic β precursor cells are human pluripotent stem cells (Fig. 1 and 0018). With respect to claim 45, Vallier teaches the composition where the pluripotent stem cells are embryonic stem cells or induced pluripotent stem cells (0020).
With respect to claims 46 and 47, Vallier teaches the culture medium not containing any albumin (0040).
Vallier does not teach the composition where the water-soluble polymer is at a concentration of about 0.04-0.06% w/v in the culture medium as recited in claim 6 or at a concentration of about 0.05% w/v in the culture medium as recited in claim 7. However, one of ordinary skill in the art would recognize that the concentration of the water-soluble polymer in the culture medium is a result effective variable and that the concentration of the water-soluble polymer would be matter of routine optimization as evidenced by Kuriyama. Kuriyama teaches a cell culture medium for stem cells containing a water-soluble polymer which can be polyvinyl alcohol as a substitute for albumin (0009, 0015, and 0023). Kuriyama teaches that the amount of a medium additive, water-soluble polymer, that is added to the basal medium is determined depending on desired effect and the kind of water-soluble polymer added (0067). Kuriyama further teaches that when the concentration of the water-soluble polymer is too low there may be affect and when it is too high it might cytotoxic (0062). Generally, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation" In re Aller, 220 F.2d 454,456, 105 USPQ 233,235 (CCPA 1955) -MPEP § 2144.05.
Vallier is silent to whether the pancreatic endocrine cell are ISL1-positive and does not teach the in vitro composition further containing NKX6.1-positive, ISL1-positive pancreatic endocrine cells as recited in claim 11.
However, Harb teaches a similar in vitro composition containing pancreatic β cells or precursor cells in a culture medium (abstract, 0004 and 00044-0045). Harb teaches the composition can including pancreatic endocrine cells that include NKX6.1-positive, ISL1-positive pancreatic endocrine cells (0006 and 0229).
Accordingly, at the effective time of filing of the claimed invention, one of ordinary skill in the art would have been motivated to modify the composition of Vallier so that the pancreatic β cells and/or precursor cells further include NKX6.1-positive, ISL1-positive pancreatic endocrine cells, for the benefit of culturing additionally known pancreatic endocrine cells as taught by Harb. It would have been obvious to one of ordinary skill in the art to include additionally known pancreatic cell types in the pancreatic cell composition of Vallier, since these cells were known in the art to be included in culture medium as taught by Harb. Additionally, one of ordinary skill in the art would have had a reasonable expectation of success in making such a modification to Vallier, since these were known pancreatic cell types which are included in in vitro cultures as taught by Harb.
Additionally, Vallier does not teach the in vitro composition containing where the composition further comprises pancreatic α cells, pancreatic δ cells, pancreatic F cells, pancreatic ɛ cells, enterochromaffin cells, or any combination thereof as recited in claim 12.
However, Harb teaches an in vitro composition containing pancreatic endocrine cells including pancreatic β cells, pancreatic α cells, pancreatic δ cells, and enterochromaffin (EC) cells (abstract).
Accordingly, at the effective time of filing of the claimed invention, one of ordinary skill in the art would have been motivated to modify the composition of Vallier so that the pancreatic β cells and/or precursor cells further include pancreatic β cells, pancreatic α cells, pancreatic δ cells, and EC cells, for the benefit of culturing additionally known pancreatic cells as taught by Harb. It would have been obvious to one of ordinary skill in the art to include additionally known pancreatic cell types in the pancreatic cell composition of Vallier, since these cells were known in the art to be included in culture medium as taught by Harb. Additionally, one of ordinary skill in the art would have had a reasonable expectation of success in making such a modification to Vallier, since these were known pancreatic cell types which are included in in vitro cultures as taught by Harb.
Vallier does not teach the in vitro composition where the precursor cells of the pancreatic β cells further contain NKX6.1-positive, ISL1-positive cells as recited in claim 19.
However, Harb teaches an in vitro composition containing pancreatic precursor cells including NKX6.1-positive, ISL1-positive cells (0017).
Accordingly, at the effective time of filing of the claimed invention, one of ordinary skill in the art would have been motivated to modify the composition of Vallier so that the pancreatic β cells and/or precursor cells further include pancreatic precursor cells including NKX6.1-positive, ISL1-positive cells, for the benefit of culturing additionally known pancreatic precursor cells as taught by Harb. It would have been obvious to one of ordinary skill in the art to include additionally known pancreatic cell types in the pancreatic cell composition of Vallier, since these cells were known in the art to be included in culture medium as taught by Harb. Additionally, one of ordinary skill in the art would have had a reasonable expectation of success in making such a modification to Vallier, since these were known pancreatic cell types which are included in in vitro cultures as taught by Harb.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-8, 11-19, 26, 27, 32-34, 38, 39, and 43-47 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-4, 7-14 and 142 of copending Application No. 18/647137 as evidenced by Kuriyama et al. (US 2017/0009200 A1) in view of Harb et al. (US 2022/0090020 A1) (ref. of record) and Vallier et al. (US 2015/0225698 A1). Although the conflicting claims are not identical, they are not patentably distinct from each other because the instant claims encompass those of the copending patent application. In addition, both claim in vitro compositions containing a population of pancreatic progenitor cells and the culture medium contains a water-soluble synthetic polymer.
Claims 1 and 10 of application No. 18/647137 recites the limitations of instant claims 1, 2, 8 and 14, of an in vitro composition containing a population of pancreatic progenitor cells in a culture medium where the pancreatic progenitor cells are PDX1-positive and NKX6.1 positive and the medium contains a water-soluble synthetic polymer. Claim 11 of application No. 18/647137 recites the limitations of instant claim 3, where the water-soluble synthetic polymer comprises polyvinyl alcohol, poloxamer, polyvinylpyrrolidone, polyethylene glycol (PEG), PEG copolymers, poly(N-isopropylacrylamide), or polyacrylamide. Claim 12 of application No. 18/647137 recites the limitations of instant claim 4, where the water-soluble synthetic polymer comprises polyvinyl alcohol.
Claim 13 of application No. 18/647137 recites the limitations of instant claim 5, where the water- soluble synthetic polymer is present at a concentration of about 0.005% to about 0.5% (w/v), about 0.01% to about 0.2% (w/v), about 0.02% to about 0.1% (w/v), or about 0.03% to about 0.08% (w/v) in the culture medium.
The claims of application No. 18/647137 do not recited the limitations of instant claim 6, where the water- soluble synthetic polymer is present at a concentration of about 0.04% to about 0.06% (w/v) in the culture medium. The claims of application No. 18/647137 do not recited the limitations of instant claim 7, where the water- soluble synthetic polymer is present at a concentration of about 0.05% (w/v) in the culture medium. However, one of ordinary skill in the art would recognize that the concentration of the water-soluble polymer in the culture medium is a result effective variable and that the concentration of the water-soluble polymer would be matter of routine optimization as evidenced by Kuriyama. Kuriyama teaches a cell culture medium for stem cells containing a water-soluble polymer which can be polyvinyl alcohol as a substitute for albumin (0009, 0015, and 0023). Kuriyama teaches that the amount of a medium additive, water-soluble polymer, that is added to the basal medium is determined depending on desired effect and the kind of water-soluble polymer added (0067). Kuriyama further teaches that when the concentration of the water-soluble polymer is too low there may be affect and when it is too high it might cytotoxic (0062).
Claims 2, 3, 8 and 9 of application No. 18/647137 recites the limitation of the in vitro composition further containing a PKC activator, γ-secretase inhibitor, RA (retinoic acid)(a retinoic acid (RA) signaling pathway activator), a sonic hedgehog (SHH) pathway inhibitor, a Rho-associated, coiled-coil containing protein kinase (ROCK) inhibitor, as disclosed in instant claims 13 and 15. Claims 4, 7-9 and 142 of application No. 18/647137 recites the limitations of the in vitro composition further containing a y-secretase inhibitor comprising XXI or DAPT, retinoic acid, Thiazovivin, SANT1, protein kinase C activator selected from the group consisting of: phorbol 12,13- dibutyrate (PDBU), TPB, phorbol 12-myristate 13-acetate, and bryostatin 1 as disclosed in instant claim 16.
Claim 14 of application No. 18/647137 recites the limitations of instant claim 17, where the water-soluble synthetic polymer comprises polyvinyl alcohol that is more than 85% hydrolyzed. The claims of application No. 18/647137 do not recited the limitations of instant claim 18, where the water- soluble synthetic polymer comprises polyvinyl alcohol that is about 87% to 89% hydrolyzed. However, one of ordinary skill in the art would recognize that the percentage of hydrolysis of the PVA in the culture medium is a result effective variable and that the percentage of hydrolysis of PVA would be matter of routine optimization as evidenced by Kuriyama. Kuriyama teaches a cell culture medium for stem cells containing a water-soluble polymer which can be polyvinyl alcohol as a substitute for albumin (0009, 0015, and 0023). Kuriyama teaches that the amount of a medium additive, water-soluble polymer, that is added to the basal medium is determined depending on desired effect and the kind of water-soluble polymer added (0067). Kuriyama teaches the PVA with a hydrolysis of 75-90% and when the hydrolysis ratio is too low, water-solubility is not sufficient and, when it is too high, hydroxyl groups of polymers form a hydrogen bond to lower the solubility and dispersibility in water.
The claims of application No. 18/647137 do not recited the limitations of instant claim 11, where the composition further comprises NKX6.1-positive, ISL1-positive pancreatic endocrine cells. The claims of application No. 18/647137 do not recited the limitations of instant claim 12, where the composition further comprises pancreatic α cells, pancreatic δ cells, pancreatic F cells, pancreatic ɛ cells, enterochromaffin cells, or any combination thereof. The claims of application No. 18/647137 do not recited the limitations of instant claim 19, where the precursor cells of the pancreatic β cells further comprise NKX6.1-positive, ISL1-positive cells.
However, Harb teaches a similar in vitro composition containing pancreatic β cells or precursor cells in a culture medium (abstract, 0004 and 00044-0045). Harb teaches the composition can including pancreatic endocrine cells that include NKX6.1-positive, ISL1-positive pancreatic endocrine cells (0006 and 0229). Harb teaches an in vitro composition containing pancreatic endocrine cells including pancreatic β cells, pancreatic α cells, pancreatic δ cells, and enterochromaffin (EC) cells (abstract). Harb teaches an in vitro composition containing pancreatic precursor cells including NKX6.1-positive, ISL1-positive cells (0017).
Accordingly, at the effective time of filing of the claimed invention, one of ordinary skill in the art would have been motivated to modify the composition of application No. 18/647137 so that the pancreatic β cells and/or precursor cells further include NKX6.1-positive, ISL1-positive pancreatic endocrine cells; further include pancreatic α cells, pancreatic δ cells, pancreatic F cells, pancreatic ɛ cells, enterochromaffin cells, or any combination thereof; or further include pancreatic precursor cells including NKX6.1-positive, ISL1-positive cells, for the benefit of culturing additionally known pancreatic endocrine types as taught by Harb. It would have been obvious to one of ordinary skill in the art to include additionally known pancreatic cell types in the pancreatic cell composition of application No. 18/647137, since these cells were known in the art to be included in culture medium as taught by Harb. Additionally, one of ordinary skill in the art would have had a reasonable expectation of success in making such a modification to application No. 18/647137, since these were known pancreatic cell types which are included in in vitro cultures as taught by Harb.
The claims of application No. 18/647137 do not recited the limitations of instant claim 26, where the composition comprises precursor cells of the pancreatic β cells which comprise a plurality of FOXA2-positive primitive gut cells. Similarly, the claims of application No. 18/647137 do not recited the limitations of instant claim 27, where the culture medium of the composition containing FOXA2-positive primitive gut cells further comprises one or more agents selected from the group consisting of: a protein kinase C activator, a growth factor from transformation growth factor 3 (TGF-(3) superfamily, a bone morphogenetic protein signaling pathway inhibitor, a growth factor from fibroblast growth factors (FGF) family, a retinoic acid (RA) signaling pathway activator, a Rho-associated, coiled- coil containing protein kinase (ROCK) inhibitor, and a sonic hedgehog (SHH) pathway inhibitor.
The claims of application No. 18/647137 do not recited the limitations of instant claim 32, where the composition comprises precursor cells of the pancreatic β cells which comprise a plurality of SOX17-positive definitive endoderm cells. Similarly, the claims of application No. 18/647137 do not recited the limitations of instant claims 33 and 34, where the culture medium of the composition containing SOX17-positive definitive endoderm cells further comprises a growth factor from fibroblast growth factors (FGF) family or where the FGF is selected from the group consisting of: keratinocyte growth factor (KGF), FGF2, FGF10, FGF21, and FGF8B.
The claims of application No. 18/647137 do not recited the limitations of instant claims 38, 44 or 45, where the composition comprises precursor cells of the pancreatic β cells which comprise a plurality of pluripotent stem cells (PSCs), where the PSCs are human or where the PSCs are embryonic stem cells or iPSCs. Similarly, the claims of application No. 18/647137 do not recited the limitations of instant claim 39, where the culture medium of the composition containing pluripotent stem cells further comprises a growth factor from transformation growth factor p (TGF-(3) superfamily, a WNT signaling pathway activator, or both. The claims of application No. 18/647137 do not recited the limitations of instant claim 39, where the composition comprising the plurality of PSC further contains SOX17-positive cells.
However, Vallier teaches an in vitro composition containing a plurality of pancreatic β cells or precursor cells and a culture medium containing polyvinyl alcohol (CDM-PVA) (0008-0014 and 0042). With respect to claim 26, Vallier teaches the composition where the pancreatic β precursor cells are FOXA2-positive primitive foregut cells (0011-0012 and 0099). With respect to claim 27, Vallier teaches the composition where the FOXA2-positive primitive foregut cells are in a medium containing the second or third pancreatic induction medium (stage 2 or stage 3) medium. Stage 2 contains SB-431542, FGF10, all-trans retinoic acid and Noggin and stage 3 contains FGF10, all-trans retinoic acid, KAAD-cyclopamine and Noggin (0011 and 0201). With respect to claim 32, Vallier teaches the composition where the pancreatic β precursor cells are SOX17-positive definitive endoderm cells (Fig. 1 and 0010-0011). With respect to claims 33 and 34, Vallier teaches the composition where the SOX17-positive definitive endoderm cells are in a medium containing the stage 1 or stage 2 medium (Fig. 1). Stage 1 medium contains Activin-A and bFGF and stage 2 contains SB-431542, FGF10, all-trans retinoic acid and Noggin (0010-0011 and 0201). With respect to claims 38 and 44, Vallier teaches the composition where the pancreatic β precursor cells are pluripotent stem cells (Fig. 1, 0007, 0009). With respect to claim 39, Vallier teaches the composition where the pluripotent stem cells are in a definitive induction medium containing TGF-β, FGF, BMP, a PI3K inhibitor, BMP and optionally a GSK3 β inhibitor (0009-0010). With respect to claim 43, Vallier teaches the composition containing SOX17-positive definitive endoderm cells which would include pluripotent stem cells as they differentiate (Fig. 1 and 0093). With respect to claim 44, Vallier teaches the composition where the pancreatic β precursor cells are human pluripotent stem cells (Fig. 1 and 0018). With respect to claim 45, Vallier teaches the composition where the pluripotent stem cells are embryonic stem cells or induced pluripotent stem cells (0020).
Accordingly, at the effective time of filing of the claimed invention, one of ordinary skill in the art would have been motivated to modify the composition of application No. 18/647137 so that the pancreatic β cells and/or precursor cells further include the additional pancreatic cell types and additional culture components listed in claims 26-27, 32-34, 38-39, and 43-45 with these pancreatic cell types, for the benefit of culturing additionally known pancreatic cell types as taught by Vallier. It would have been obvious to one of ordinary skill in the art to include additionally known pancreatic cell types in the pancreatic cell composition of application No. 18/647137, since these cells were known in the art to be included in culture medium with the claimed factors as taught by Vallier. Additionally, one of ordinary skill in the art would have had a reasonable expectation of success in making such a modification to application No. 18/647137, since these were known pancreatic cell types which are included in in vitro cultures with the claimed factors as taught by Vallier.
The claims of application No. 18/647137 do not recited the limitations of instant claim 46, where the culture medium does not comprise an albumin protein. Similarly, The claims of application No. 18/647137 do not recited the limitations of instant claim 47, where the culture medium does not comprise a human serum albumin (HSA).
However, Vallier teaches an in vitro composition containing a plurality of pancreatic β cells or precursor cells and a culture medium containing polyvinyl alcohol (CDM-PVA) (0008-0014 and 0042). Vallier teaches the culture medium not containing any albumin so that the medium is chemically defined and there are no unknown components (0040).
Accordingly, at the effective time of filing of the claimed invention, one of ordinary skill in the art would have been motivated to modify the composition of application No. 18/647137 so that the medium does not include albumin protein or human serum albumin, for the benefit of having chemically defined medium as taught by Vallier. It would have been obvious to one of ordinary skill in the art to exclude albumin in the culture medium composition of application No. 18/647137, since these cells were known in the art to be included in culture medium that do not contain albumin as taught by Vallier. Additionally, one of ordinary skill in the art would have had a reasonable expectation of success in making such a modification to application No. 18/647137, since similar compositions containing pancreatic cells and a culture medium with a water-soluble synthetic polymer as taught by Vallier.
Conclusion
No claims are allowed.
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/EMILY A CORDAS/Primary Examiner, Art Unit 1632
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