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 .
Election/Restrictions
Applicant’s election without traverse of Group V, claims 8, 9, 11 and 82 in the reply filed on 5/21/2026 is acknowledged.
Applicant has cancelled all non-elected claims.
Applicant has set forth new claims 221-262.
Claims 8, 9, 11, 82 and 221-262 are examined in the instant application.
Claim Rejections - 35 USC § 102
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 (i.e., changing from AIA to pre-AIA ) 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.
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.
Claim(s) 8, 9, 11, 82, 231-235, 239, 241, 242, 245-250 and 253-261 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hebrok et al. (WO 2017 /019702 Al).
Regarding claims 8, 9 and 82, Hebrok et al. teach method of producing an in vitro composition comprising contacting a plurality of PDX1/NKX6.1 positive, insulin negative cells with 0.1-5 mM glutamine (pg. 7 lines 19-37).
Regarding claims 11, 231 and 232, while Hebrok does not explicitly state that there glutamine is a not in a alanine-dipeptide form, it is interpreted that the glutamine of Hebrok is an L-glutamine in a free form (NOT in an alanine-glutamine dipeptide form) since Hebrok uses both glutamine and Glutamax (which is in an alanine-dipeptide form).
Regarding claim 233, Hebrok teaches that the composition further comprises a plurality of insulin-positive endocrine progenitor cells (pg. 83 lines 1-3 and Fig. 5B).
Regarding claims 234 and 235, Hebrok teaches that the composition comprises about 1 mM acetate and 50-1000 nM of acetate (pg. 76 lines 20-35).
Regarding claim 239, Hebrok teaches that the composition can comprise vitamin C (pg. 103 lines 24-29).
Regarding claims 241 and 242, Hebrok teaches that the composition can comprise LDN193189 (pg. 105 lines 21-24).
Regarding claims 245 and 246, Hebrok teaches that the composition can comprise a histone methyltransferase inhibitor such as UNC0638 (pg. 108 lines 5-8).
Regarding claims 247-250, Hebrok teaches that the composition can comprise ALK5 inhibitor II and T3 (pg. 113 lines 10-20).
Regarding claims 253 and 254, Hebrok teaches that the composition can comprise cyclopamine (pg. 6 line 34).
Regarding claims 255 and 256, Hebrok teaches that the composition can comprise EGF (pg. 6 lines 1-22).
Regarding claims 257 and 258, Hebrok teaches that the composition can comprise DAPT (pg. 62 line 5).
Regarding claims, 259 and 260, Hebrok teaches that the composition can comprise ZnSO4 (pg. 76 lines 20-28).
Regarding claim 261, Hebrok teaches that the composition can comprise citrate (an acetyl-CoA related metabolite (pg. 41 line 10 bridge pg. 42 line 3).
Thus the teachings of Hebrok clearly anticipate the invention of claims 8, 9, 11, 82, 231-235, 239, 241, 242, 245-250 and 253-260.
Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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.
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.
Claim(s) 8 and 236 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hebrok et al. (WO 2017 /019702 Al) in view of Sampson et al. (2017, J. Insulin Resistance, Vol. 2(1), pgs. 1-8).
Regarding claim 8, Hebrok et al. teach an in vitro composition comprising a plurality of PDX1/NKX6.1 positive, insulin negative cells with 0.1-5 mM glutamine (pg. 7 lines 19-37).
Hebrok does not teach:
Using β-hydroxybutyrate.
Regarding β-hydroxybutyrate, Sampson et al. teach that β-hydroxybutyrate
can improve pancreatic cell survival and proliferation (see Abstract) and mitochondrial function (Fig. 3).
Thus at the time of filing the ordinary artisan would have found it prima facie obvious to combine the teachings of Hebrok regarding an in vitro composition comprising a plurality of PDX1/NKX6.1 positive, insulin negative cells with the teachings of Sampson regarding the benefits of using β-hydroxybutyrate to arrive at the claimed invention.
One of ordinary skill in the art would have been motivated to make such a combination since Samspson teaches that it was known at the time of filing that β-hydroxybutyrate can improve the survival an proliferation of pancreatic cells.
There would have been a reasonable expectation of success that the composition of Hebrok could comprise β-hydroxybutyrate since Sampson teaches that β-hydroxybutyrate successfully works with pancreatic cells.
Thus the cited art provides the requisite teachings and motivations to make and use the invention as claimed.
Claim(s) 8 and 237 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hebrok et al. (WO 2017 /019702 Al) in view of Idrissi et al. (2009, Adv. Exp. Med. Biol, Vol. 64, Abstract only).
Regarding claim 8, Hebrok et al. teach an in vitro composition comprising a plurality of PDX1/NKX6.1 positive, insulin negative cells with 0.1-5 mM glutamine (pg. 7 lines 19-37).
Hebrok does not teach:
Using taurine.
Regarding taurine, Idrissi et al. teach that taurine can be an important factor for
development of the endocrine pancreas and may reduce apoptosis cytokine-induced apoptosis (see Abstract).
Thus at the time of filing the ordinary artisan would have found it prima facie obvious to combine the teachings of Hebrok regarding an in vitro composition comprising a plurality of PDX1/NKX6.1 positive, insulin negative cells with the teachings of Idrissi regarding the benefits of using taurine to arrive at the claimed invention.
One of ordinary skill in the art would have been motivated to make such a combination since Idrissi teaches that it was known at the time of filing that taurine can improve the development of endocrine cells and prevent their apoptosis.
There would have been a reasonable expectation of success that the composition of Hebrok could comprise taurine since Idrissi teaches that taurine successfully works with pancreatic cells.
Thus the cited art provides the requisite teachings and motivations to make and use the invention as claimed.
Claim(s) 8 and 238 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hebrok et al. (WO 2017 /019702 Al) in view of Nadler et al. (WO 2007/146786 A1).
Regarding claim 8, Hebrok et al. teach an in vitro composition comprising a plurality of PDX1/NKX6.1 positive, insulin negative cells with 0.1-5 mM glutamine (pg. 7 lines 19-37).
Hebrok does not teach:
Using formate.
Regarding formate, Nadler et al. teach that formate is a factor for
development of pancreatic endocrine cells (parags. 20 and 130).
Thus at the time of filing the ordinary artisan would have found it prima facie obvious to combine the teachings of Hebrok regarding an in vitro composition comprising a plurality of PDX1/NKX6.1 positive, insulin negative cells with the teachings of Nadler regarding the role of formate in pancreas development to arrive at the claimed invention.
One of ordinary skill in the art would have been motivated to make such a combination since Nadler teaches that it was known at the time of filing that formate can facilitate the differentiation of cells into pancreatic β cells.
There would have been a reasonable expectation of success that the composition of Hebrok could comprise formate since Nadler teaches that formate successfully works with pancreatic cells.
Thus the cited art provides the requisite teachings and motivations to make and use the invention as claimed.
Claim(s) 8 and 240 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hebrok et al. (WO 2017 /019702 Al) in view of Vega-Monroy et al. (2013, J. Nutritional Biochemistry, Vol. 24, pgs. 169-177).
Regarding claim 8, Hebrok et al. teach an in vitro composition comprising a plurality of PDX1/NKX6.1 positive, insulin negative cells with 0.1-5 mM glutamine (pg. 7 lines 19-37).
Hebrok does not teach:
Using biotin.
Regarding biotin, Vega-Monroy et al. teach that pharmacological
concentrations of biotin enhance insulin secretion and the expression of genes and signaling pathways that favor islet function in vitro (see Abstract).
Thus at the time of filing the ordinary artisan would have found it prima facie obvious to combine the teachings of Hebrok regarding an in vitro composition comprising a plurality of PDX1/NKX6.1 positive, insulin negative cells with the teachings of Vega-Monroy regarding the role of biotin on islet cell function to arrive at the claimed invention.
One of ordinary skill in the art would have been motivated to make such a combination since Vega-Monroy teaches that it was known at the time of filing that biotin is beneficial for cells of the pancreatic islet.
There would have been a reasonable expectation of success that the composition of Hebrok could comprise biotin since Vega-Monroy teaches that biotin successfully works with pancreatic cells.
Thus the cited art provides the requisite teachings and motivations to make and use the invention as claimed.
Claim(s) 8, 243 and 244 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hebrok et al. (WO 2017 /019702 Al) in view of Agulnick et al. (US 2010/0272695 A1).
Regarding claim 8, Hebrok et al. teach an in vitro composition comprising a plurality of PDX1/NKX6.1 positive, insulin negative cells with 0.1-5 mM glutamine (pg. 7 lines 19-37).
Hebrok does not teach:
Using a ROCK inhibitor.
Regarding the ROCK inhibitor Y-27632, Agulnick et al. teach using the ROCK
inhibitor Y-27632 to promote the expansion and survival of differentiated pancreatic progenitor cells (parags. 206-208).
Thus at the time of filing the ordinary artisan would have found it prima facie obvious to combine the teachings of Hebrok regarding an in vitro composition comprising a plurality of PDX1/NKX6.1 positive, insulin negative cells with the teachings of Agulnick regarding the benefits of using a ROCK inhibitor to arrive at the claimed invention.
One of ordinary skill in the art would have been motivated to make such a combination since Agulnick teaches that using a ROCK inhibitor can increase survival and proliferation of pancreatic progenitor cells.
There would have been a reasonable expectation of success that the composition of Hebrok could comprise a ROCK inhibitor since Agulnick teaches combining pancreatic progenitor cells with a ROCK inhibitor.
Thus the cited art provides the requisite teachings and motivations to make and use the invention as claimed.
Claim(s) 8, 251 and 252 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hebrok et al. (WO 2017 /019702 Al) in view of Peterson et al. (US Pat. No. 10,030,229 B2, issued 7/24/2018).
Regarding claim 8, Hebrok et al. teach an in vitro composition comprising a plurality of PDX1/NKX6.1 positive, insulin negative cells with 0.1-5 mM glutamine (pg. 7 lines 19-37).
Hebrok does not teach:
Using staurosporine.
Regarding staurosporine, Peterson et al. teach that staurosporine
can be contacted with cells that are NKX6.1 positive to insulin-positive endocrine cells (col. 65 lines 1-13).
Thus at the time of filing the ordinary artisan would have found it prima facie obvious to combine the teachings of Hebrok regarding an in vitro composition comprising a plurality of PDX1/NKX6.1 positive, insulin negative cells with the teachings of Peterson regarding the role of staurosporine on pancreatic cell differentiation to arrive at the claimed invention.
One of ordinary skill in the art would have been motivated to make such a combination since Peterson teaches that it was known at the time of filing that staurosporine can differentiate NKX6.1 positive cells into insulin expressing cells.
There would have been a reasonable expectation of success that the composition of Hebrok could comprise staurosporine since Peterson teaches that staurosporine successfully works with pancreatic cells.
Thus the cited art provides the requisite teachings and motivations to make and use the invention as claimed.
Claim(s) 8 and 262 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hebrok et al. (WO 2017 /019702 Al) in view of Priyadarshini et al. (2015, Mol. Endocrinol., Vol. 29(7), pgs. 1055-1066).
Regarding claim 8, Hebrok et al. teach an in vitro composition comprising a plurality of PDX1/NKX6.1 positive, insulin negative cells with 0.1-5 mM glutamine (pg. 7 lines 19-37).
Hebrok does not teach:
Using acetate.
Regarding acetate, Priyadarshini et al. teach that 1mM of acetate can regulate
insulin-secretion in endocrine cells (pg. 1061 col. 2 last line bridge pg. 1062 col. 2 lines 1-3 and Fig. 3).
Thus at the time of filing the ordinary artisan would have found it prima facie obvious to combine the teachings of Hebrok regarding an in vitro composition comprising a plurality of PDX1/NKX6.1 positive, insulin negative cells with the teachings of Priyadarshini regarding the role of acetate in insulin-secretion to arrive at the claimed invention.
One of ordinary skill in the art would have been motivated to make such a combination since Priyadarshini teaches that it was known at the time of filing that acetate can stimulate insulin secretion.
There would have been a reasonable expectation of success that the composition of Hebrok could comprise acetate since Priyadarshini teaches that acetate successfully works with pancreatic cells.
Thus the cited art provides the requisite teachings and motivations to make and use the invention as claimed.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID A MONTANARI whose telephone number is (571)272-3108. The examiner can normally be reached M-Tr 8-6.
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/DAVID A MONTANARI/Examiner, Art Unit 1632
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