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 of Group II, claims 10-12, 14 and 68-76 in the reply filed on 3/23/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 43, 47, 48, 51, 53, 54, 56, 58, 60, 61, 63, 64 and 67 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 3/23/2026.
Claim Rejections - 35 USC § 112
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 10-12, 14 and 68-76 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for:
a method of differentiating induced pluripotent stem cells (iPSCs) into induced pancreatic (iPan) ductal cells, comprising:
seeding iPSCs on a solid medium coated with solubilized basement membrane
preparation in the presence of serum-free, stabilized cell culture medium, and optionally a ROCK inhibitor,
culturing the cells in a first culture medium comprising a first base medium, Activin
A, CHIR99021, and a ROCK inhibitor to obtained definitive endoderm cells,
(c) culturing the definitive endoderm cells in a second culture medium comprising the first base medium and Activin A and bFGF (FGF-2) to obtain pancreatic foregut cells,
(d) culturing the pancreatic foregut cells in a third culture medium comprising the first base medium and FGF10, NOGGIN, and CHIRR99021 to obtain bipotent trunk progenitor (BTP) cells,
(e) culturing the BTP cells in a fourth culture medium comprising a second base medium and FGF10, NOGGIN, All-trans Retinoic Acid, and SANT1 for two days to obtain pancreatic progenitor cells,
(f) seeding the pancreatic progenitor cells on a solid medium coated with solubilized basement membrane preparation in the presence of a fifth culture medium comprising a second base medium and a ROCK inhibitor; and
(g) culturing the cells in a sixth culture medium comprising the second base medium and FGF10, EGF, and sDLL-1, wherein iPan ductal cells are produced,
does not reasonably provide enablement for:
culturing BTP cells for any amount of time with FGF10, NOGGIN, All-trans Retinoic Acid, and SANT1 for any amount of time other than two days.
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.
While determining whether a specification is enabling, one considers whether the claimed invention provides sufficient guidance to make and use the claimed invention, if not, whether an artisan would have required undue experimentation to make and use the claimed invention and whether working examples have been provided. When determining whether a specification meets the enablement requirements, some of the factors that need to be analyzed are: the breadth of the claims, the nature of the invention, the state of the prior art, the level of one of ordinary skill, the level of predictability in the art, the amount of direction provided by the inventor, the existence of working examples, and whether the quantity of any necessary experimentation to make or use the invention based on the content of the disclosure is ''undue'' (In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)). Furthermore, USPTO does not have laboratory facilities to test if an invention will function as claimed when working examples are not disclosed in the specification, therefore, enablement issues are raised and discussed based on the state of knowledge pertinent to an art at the time of the invention, therefore skepticism raised in the enablement rejections are those raised in the art by artisans of expertise.
The breadth of the claimed invention encompasses producing iPan cells using any length of time when producing pancreatic progenitor cells from BTP cells.
However, a review of the instantly filed specification teaches that the claimed method
requires a step-by-step differentiation protocol to differentiate iPS cells into iPan cells that requires specific days to of culturing at step (e) (aka Phase III in the specification).
Working Examples
The specification teaches that to produce the claimed iPan cells from iPS cells requires a specific incubation period of two days during Phase III of their culturing protocol. Specifically, the specification teaches in parag. 205 and illustrated in Fig. 1C (reproduced below):
“To confirm that Phase III should be shortened, we tested ductal differentiation protocol with either 2 or 4 days of Phase III treatment, followed by ductal specification in Phase IV, which entailed addition of EGF, FGF110 and sDLL1 to the cultures. After 2 days of Phase III treatment, we found increased levels of ductal markers, whereas a 4-day Phase III treatment was associated with increased levels of the pancreatic endocrine NKX6.1 (Figure 1B). Figure 1C shows the final version of our optimized iPan Ductal differentiation schedule with 4 days of Definitive Endoderm specification, 2 days of Posterior Foregut specification, 2 days of Bipotent Trunk Progenitors specification, then terminal iPan Ductal maturation for 2 weeks or longer.”
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This teaching is further supported by the results in Fig. 7 which teaches that
“Unfortunately, pancreatic endocrine marker C-Peptide was elevated, and no increase in ductal markers were found on Day 21 (Figure 7), indicating that the initiating ductal specification at the pancreatic endoderm stage was too late to effectively elicit ductal phenotype by activation of Notch signaling.” (parag. 203 last 5 lines).
Thus the skilled artisan can conclude from the teachings in the specification that the timing of culturing at Phase III (step (e) in the scope above) is critical to the enablement of the claimed method. Culturing longer than 2 days at step (e) results in producing pancreatic endocrine cells, which are distinct from the claimed iPan ductal cells which are epithelial cells. The art further supports these teachings in the specification that the timing of exposing to growth factors is critical to obtaining a desired cell type.
For example, Cell Guidance Systems (August 2024, 4 page printout attached) teaches:
“Growth factors are critical to many aspects of cell culture including proliferation, differentiation and cell maintenance. While the effects of too-little growth factors, such as lack of proliferation, are readily apparent, adding too much growth factor, though less obvious can be equally important.
Similar to drugs, as well as their desired effects, growth factors can have a myriad of unwanted side effects. Just as drugs have therapeutic windows in which the drug has efficacy and tolerable side effects, there is an optimal range for growth factors used in culture.” (pg. 1 lines 1-7).
Conclusion
Thus, as set forth above, the claimed method is not enabled for its entire breadth. As the specification and the art teaches above, the skilled artisan would find that only through a culturing of BTS cells for two days with FGF10, NOGGIN, All-trans Retinoic Acid, and SANT1 could the claimed iPan cells be obtained by the claimed method. Thus, the claims are not enabled for their entire breadth and thus limiting the claimed invention to the scope set forth above is proper.
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 10-12, 14 and 68-76 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 10 is unclear. Claim 10 appears to recite two distinct methods due to the use of the operator “or” following the step of producing pancreatic progenitors. Thus it is not clear how the iPan cells are produced before the recitation of “or” since only pancreatic progenitors are produced. Further it is not clear how the culture mediums are “fifth” and “sixth” since they should be “first” and “second” mediums if the alternate method starts with pancreatic progenitor cells. Thus it is not clear that the metes and bounds are of the claimed method(s) set forth in claim 10 due to the recitation of “or”.
Claim 70 contains the trademark/trade name MATRIGEL. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe MATRIGEL and, accordingly, the identification/description is indefinite.
Claim 70 contains the trademark/trade name mTeSRTM. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe mTeSRTM and, accordingly, the identification/description is indefinite.
Claim 71 contains the trademark/trade name Glutamax. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe Glutamax and, accordingly, the identification/description is indefinite.
Claim 71 contains the trademark/trade name B27. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe B27 and, accordingly, the identification/description is indefinite.
Claim 72 contains the trademark/trade name Glutamax. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe Glutamax and, accordingly, the identification/description is indefinite.
Claim 72 contains the trademark/trade name B27. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe B27 and, accordingly, the identification/description is indefinite.
Claim 73 contains the trademark/trade name Glutamax. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe Glutamax and, accordingly, the identification/description is indefinite.
Claim 74 contains the trademark/trade name B27. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe B27 and, accordingly, the identification/description is indefinite.
Claim 75 contains the trademark/trade name B27. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe B27 and, accordingly, the identification/description is indefinite.
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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