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 64-75 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.
Claim Objections
Claims 64, 66, 69, and 73-75 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 as synonymous (see instant [0097]). 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.
Claim Interpretation
In claim 64, the phrase “thereby generating a first population of cells” is interpreted as meaning merely producing a population of PDX.1-positive, NKX6.1-positive pancreatic progenitor cells which have been contacted with an FGF family growth factor, such as after a millisecond of contacting.
It is noted that in claims 67 and 73-75, there is no limitation as to any order of the method steps (see MPEP 2111.01(II)), meaning the cells may be contacted with the FGF or serum albumin protein in any order or simultaneously for claim 67 and 73, and that the cells may be contacted with the FGF or the recited inhibitor/activator/modifier in any order or simultaneously for claim 74 and 75. It is also noted that none of the contactings in claims 64, 66-69 and 73-75 recite any minimum amount.
Due to the recitation of the transition phrase “further comprises,” claim 68 is interpreted as requiring contacting the first population of cells with at least one agent in addition to the FGF family growth factor even if that FGF family growth factor is encompassed by the functionally described agent(s) recited in claim 68.
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.
In claim 71, the term “insulin-positive” cell is interpreted as meaning a cell that expresses a detectable amount of insulin protein (see [0092]), and thus, in claim 70, the term “insulin-negative” is interpreted as meaning no detectable insulin protein.
In claim 72, the term “C-peptide positive” is interpreted as meaning a cell that expresses C-peptide.
Claim 75 is interpreted as encompassing merely wherein the method of claim 69 is performed with the FGF family growth factor is selected from FGF1-10 and FGF 15-23, as these each may function as a PKC activator.
Claim Rejections - 35 USC § 112(a) - Written Description
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 64 and 66-75 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the 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 claimed invention.
The claimed invention as a whole is not adequately described if the claims require essential or critical elements that are not adequately described in the specification and that is not conventional in the art as of applicant’s effective filing date. Possession may be shown by actual reduction to practice, clear depiction of the invention in a detailed drawing, or by describing the invention with sufficient relevant identifying characteristics such that a person skilled in the art would recognize that the inventor had possession of the claimed invention. Pfaff v. Wells Electronics, Inc., 48 USPQ2d 1641,1646 (1998).
In making a determination of whether the application complies with the written description requirement under 35 U.S.C. 112(a) or 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant is claiming and what Applicant has possession of.
Claims 64 and 69 are directed to methods of (1) contacting PDX.1-positive NKX6.1-positive cells in a cell population with an FGF family growth factor. When analyzed in light of the specification, the claims are broad in that “FGF family growth factor” encompasses a broad genus of factors. Claims 66, 68, and 74 are dependent claims of the aforementioned that are broad as explained below in that the methods also comprise contacting the cell population with an agent selected from: a “TGF-β pathway inhibitor,” “BMP signaling pathway inhibitor,” “protein kinase inhibitor,” “epigenetic modifier,” “SHH pathway inhibitor,” and “PKC activator.”
The term “FGF family growth factor” is not defined by the claims or the instant application (see [0359]-[0363]) and, thus, takes its ordinary meaning in the art. The prior art teaches the FGF family encompasses various factors, including the FGF11 subgenus which don’t bind FGF receptors as well as the FGF19 subgenus which act as hormones instead of growth factors (see e.g., Xie et al., Signal Transduct Target Ther 5: 181 (2020) at pg. 16, right col.). Thus, not all FGFs are functionally equivalent with each other and, thus, do not a priori provide predictable results. Furthermore the instant application provides no hint of a nexus amongst all FGF family members and all working examples are based solely on FGF2.
Similarly, the terms “TGF-β pathway inhibitor,” “BMP signaling pathway inhibitor,” “protein kinase inhibitor,” “epigenetic modifier,” “SHH pathway inhibitor,” and “PKC activator” are not defined beyond their eponymic functional definitions. However each of the aforementioned terms encompasses a broad genus due to specific guidance in the instant specification.
(1) A “TGF-β pathway inhibitor” is described as encompassing any analog or derivative of an ALK5 inhibitor II ([0352]; [0328]).
(2) A “BMP signaling pathway inhibitor” is described as encompassing any derivative, analogue, or variant of DMH-1 or LDN193189 ([0346]-[0348]; [0328]).
(3) A “protein kinase inhibitor” is described as encompassing any analog of staurosporine and any derivative, analogue or variant of, inter alia, bisindolylmaleimide I, bisindolylmaleimide II, bisindolylmaleimide Ill, hydrochloride, pseudohypericin, and indorublin-3-monoximc 5-Iodo ([0390]-[0394]).
(4) A “epigenetic modifier” is described as any chemical compound that can make epigenetic changes without changing DNA sequences ([0100]) as well as encompassing any variant of vorinostat, romidepsin (Istodax), chidamide, panobinostat (farydak), belinostat (PXD101), panobinostat (LBH589), valproic acid, mocetinostat (MGCD0103), abexinostat (PCI-24781), entinostat (MS-275), SB939, resminostat (4SC-201), givinostat (ITF2357), quisinostat (JNJ-26481585), HBI-8000, (a benzamide HDI), kevetrin, CUDC-101, AR-42, CHR-2845, CHR-3996, 4SC-202, CG200745, ACY-1215, ME-344, and sulforaphane ([0388]).
(5) A “SHH pathway inhibitor” is described as encompassing Sonic hedgehog antagonists and any derivative of Sant1, Sant2, Sant4, Sant4, Cur61414, forskolin, tomatidine, AY9944, triparanol, or cyclopamine ([0328]).
(6) A “PKC activator” is described as a kinase, DAG-binding molecule, or PS-binding molecule, such as a phorbol ester, polyunsaturated fatty acid, bryostatin or any derivative of bryostatin 1, any DAG derivative, or even FGF-18 ([0375]-[0376]; [0328]).
Thus, these claims encompass any derivative of, inter alia, an ALK5 inhibitor II, DMH-1, LDN193189, bisindolylmaleimide I, vorinostat, Sant1, bryostatin, and/or DAG.
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their structure. In the instant case, nowhere does the instant specification describe any derivatives, analogs, or variants, leaving the skilled artisan unguided to investigate the prior art for such species. Although the specification sufficiently describes representative species of “TGF-β pathway inhibitor,” “BMP signaling pathway inhibitor,” “protein kinase inhibitor,” “epigenetic modifier,” “SHH pathway inhibitor” (Shh antagonist), and “PKC activator.” The instant specification is silent as to any limits on the scope a derivative, analogue, analog, or variant. Furthermore, the specification fails to provide guidance as to how to determine whether a given compound is a species of the genus encompassing any derivative, analogue, analog, or variant of said agents. The prior is silent as to any standard bounds for such derivatives, analogues, analogs, and variants, either structurally or functionally.
Thus, this limited descriptive information is not deemed sufficient to reasonably convey to one skilled in the art that applicant is in possession of the methods recited any derivative, analog, or variant of the recited agents. The skilled artisan could not rely upon the disclosure in the specification such that the specification would sufficiently describe that Applicant was in possession of the entire scope of the claimed methods.
Claim Rejections - 35 USC § 112(b)
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 64-75 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.
The claims are interpreted as set forth in a previous section.
In claims 64 and 66, the term “progenitor cell” is defined by the instant specification as a cell that has a cellular phenotype that is more primitive (e.g., is at an earlier step along a developmental pathway or progression than is a fully differentiated cell) relative to a cell which it can give rise to by differentiation (e.g., pancreatic cell) (see [0084]; [0095]). Claims 64 and 66 are indefinite because the term “pancreatic progenitor cells” definition relies on the relative term “more” / ”earlier” and there is no definition provided for any “primitive” or “earlier” pancreatic cellular phenotype(s) and, thus, a person of ordinary skill in the art reading the claim would not understand the metes and bounds of a “more” primitive pancreatic cell versus a fully differentiated pancreatic cell or an “earlier” developmental step versus a later developmental step. Claims 65 and 67-68 are included in this rejection for depending from indefinite claim 64.
Claims 66 and 74 each recites a “TGF-β pathway inhibitor,” which is functionally defined in the claim and described in the instant specification as encompassing any analog or derivative of an ALK5 inhibitor II ([0352]). A person of ordinary skill in the art reading the claim would not understand the metes and bounds of the relative term “analog” or “derivative” because neither the claim nor the instant application provides any definition or standard for determining whether a giving compound structure is an analog or not, or similarly is a derivative or not. See MPEP 2173.05(b). Thus, one of ordinary skill in the art would not be reasonably appraised of the scope of this claim limitation.
Claims 66 and 74 each recites a “BMP signaling pathway inhibitor,” which is functionally defined in the claim and described in the instant specification as encompassing any derivative, analogue, or variant of DMH-1 or LDN193189 ([0346]-[0348]). A person of ordinary skill in the art reading the claim would not understand the metes and bounds of the relative terms “derivative,” “analogue” and “variant” because neither the claim nor the instant application provides any definition or standard.
Claims 66 and 74 each recites a “epigenetic modifier,” which is functionally defined in the claim and described in the instant specification as encompassing any variant of vorinostat, romidepsin, chidamide, panobinostat, belinostat, panobinostat, valproic acid, mocetinostat, abexinostat, entinostat, SB939, resminostat, givinostat, quisinostat, HBI-8000, kevetrin, CUDC-101, AR-42, CHR-2845, CHR-3996, 4SC-202, CG200745, ACY-1215, ME-344, and sulforaphane ([0388]). A person of ordinary skill in the art reading the claim would not understand the metes and bounds of the relative term “variant” because neither the claim nor the instant application provides any definition or standard.
Claims 66 and 74 each recites a “protein kinase inhibitor,” which is functionally defined in the claim and described in the instant specification as encompassing any analog of staurosporine and any derivative, analogue or variant of, inter alia, bisindolylmaleimide I, bisindolylmaleimide II, bisindolylmaleimide Ill, hydrochloride, pseudohypericin, and indorublin-3-monoximc 5-Iodo ([0390]-[0394]). A person of ordinary skill in the art reading the claim would not understand the metes and bounds of the relative terms “analog,” “derivative,” “analogue” and “variant” because neither the claim nor the instant application provides any definition or standard.
Claims 66 and 74 each recites the same list of agents defined only functionally therein involved in a contacting step, which is incoherent, ambiguous and unclear as to whether an additional contacting step is required or if all limitations of the claim can be fulfilled by the FGF family growth factor “contacting” step of the independent claim from which it depends. For example, claims 66 and 74 recite a “TGF-β pathway inhibitor,” which encompasses members of the FGF family (inhibit TGF-β-induced Smad activation, often via ERK1/2 phosphorylation) (Xie et al., at pg. 15, left col., 1st para.). Claims 66 and 74 recite a “BMP signaling pathway inhibitor,” which encompasses members of the FGF family (e.g., ones that inhibit SMAD1 in neural precursor cells or mesoderm development) (Bilican et al., PLoS One 3: e2863 (2008) at abstract). Claims 66 and 74 recite a “SHH pathway inhibitor,” which encompasses members of the FGF family (e.g., ones that inhibit Shh signaling in neural precursor cells) (Fogarty et al., PNAS 104: 2973-8 (2007) at abstract). Claims 66 and 74 recite a “protein kinase inhibitor,” which encompasses members of the FGF family (e.g., ones that drive MKP3 activity that inhibits kinases such as ERK1/2) (Li et al., Development 134: 167-76 (2007) at abstract). Claims 66 and 74 recite a “epigenetic modifier,” which encompasses members of the FGF family (e.g., ones that modify Histone H3 K27 methylation status in some situations) (Xie et al., at pg. 5, right col., 1st para.). These claims are each incoherent, ambiguous and unclear as to whether an additional contacting step is required or if all limitations of the claim can be fulfilled by a subset of the “contacting” step of the independent claim from which it depends based on the scope of FGF family growth factors encompassed. Therefore, a person of ordinary skill in the art reading the claim would not understand the metes and bounds of theses ambiguous limitations.
Claim 69 recites the term “population of PDX.1-positive and NKX6.1-positive,” which is incoherent and unclear as to what constitutes this population. Claims 70-75 are included in this rejection for depending from indefinite claim 69.
Claim 73-75 each recites the term “the population of PDX.1-positive, NKX6.1-positive cells,” which lacks sufficient antecedent basis in the claims.
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 64-65, 67, and 69-73 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Donadel (Donadel et al., Int J Mol Sci 18: 2234 (2017)).
The claims are interpreted as set forth in a previous section.
Regarding claims 64-65 and 69, Donadel discloses methods of contacting cell populations comprising PDX-1+ Nkx6.1+ pancreatic precursor cells (PANC-1 derived) with the FGF family growth factor FGF2 in cell culture (pg. 3, pg. 4, 2nd para., Fig. 2-3).
Regarding claims 67 and 73, Donadel discloses wherein the cell population is contacted with a serum albumin protein (bovine serum albumin (BSA)) (pg. 12, 3rd para.).
Regarding claim 70, although Donadel discloses wherein the cell population comprises insulin-expressing cells, not all the cells in the population exhibited insulin expression via immunofluorescence (Fig. 2).
Regarding claims 71-72, Donadel discloses wherein the cell population comprises insulin-expressing cells and C-peptide expressing cells (Fig. 2-3).
Thus, Donadel anticipates claims 64-68.
Claims 64-75 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Donadel (Donadel et al., Int J Mol Sci 18: 2234 (2017)) as evidenced by Xie (Xie et al., Signal Transduct Target Ther 5: 181 (2020)).
Regarding claims 66, 68 and 74, FGF2 is a TGF-β pathway inhibitor as evidenced by Xie (pg. 15, left col., 1st para.) and, thus, the method of Donadel comprises contacting the cells in the population with a TGF-β pathway inhibitor.
Regarding claim 74, FGF2 and classical FGFR signaling comprises PKC activation and FGF2 is a PKC activator as evidenced by Xie (Fig. 2) and, thus, the method of Donadel comprises contacting the cells in the population with a PKC activator.
Conclusion
No claim is allowed.
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/ERIC J ROGERS/Examiner, Art Unit 1638
/KEVIN K HILL/Primary Examiner, Art Unit 1638