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 1-3, 5, 7, 9, 11-18, 20, 24-26, and 28-32 are currently pending in this application.
Election/Restrictions
Applicant’s election with traverse of Group I, claims 1-3, 5, 7, 9, 12, and 15-16, in the reply filed on Dec. 2, 2025 is acknowledged. The traversal is on the ground(s) that there would not be a serious or undue burden. This is not found persuasive because burden is immaterial to a finding of lack of unity of invention pursuant to Patent Cooperation Treaty (PCT) Rule 13.1. See MPEP 1893.03(d). The requirement is made final. Claims 11, 13-14, 16-18, 20, 24-26, and 28-32 have been withdrawn from consideration as being drawn to non-elected subject matter, and claims 1-3, 5, 7, 9, 12, and 15-16 have been considered on the merits.
Specification Objections
The disclosure is objected to because of the following informalities:
The disclosure is objected to because it contains references to colors within the drawings; however, the drawings lack any color. For example, pg. 6 and pg. 10 refers to “(red)”, “(blue)”, “(orange)”, and “(green)” in FIGs 3 and 9. Appropriate correction is required.
Claim Objections
Claim 12 is objected to because of the following informalities:
Claim 12 recites “PDGFRb+ cells” from “the population of endocardial cells” made by the “producing” step of claim 1, which is unclear as to their NKX2-5 and CD31 status. For clarity, appropriate correction is requested, such as by rephrasing as “PDGFRb+ NKX2-5+ CD31+ cells.”
Claim Interpretation
Although claim 1 mentions culture conditions, claim 1 is not interpreted to require any “culturing” step.
In claim 1, the phrase “the population of endocardial cells is phenotypically NKX2-5+ and CD31+” is interpreted under a broadest reasonable interpretation to encompass the population of cells comprising (1) endocardial cells expressing NKX2-5 and CD31, or (2) a subset of endocardial cells expressing NKX2-5 but not CD31 combined with another subset of cells expressing CD31 but not NKX2-5, or (3) a combination of the aforementioned. Furthermore based on dependent claims 9 and 12, at least some of the endocardial cells produced by claim 1 are inherently (1) GATA4+, GATA5+, NFATC1+, NPR3+ and NRG1+; (2) “ENG(CD105)+ and/or (3) PDGFRb+. Similarly in claim 9, the phrase “the population of endocardial cells is phenotypically GATA4+, GATA5+, NFATC1+, NPR3+ and NRG1+” or “ENG(CD105)+” is interpreted to encompass populations of cells merely further comprising subsets of endocardial cells expressing NKX2-5 and CD105 or CD31 and CD105; and to encompass populations of cells comprising subsets of NKX2-5+ and/or CD31+ endocardial cells expressing less than all five of GATA4, GATA5, NFATC1, NPR3 and NRG1 so long as other subsets of NKX2-5+ and/or CD31+ endocardial cells are present in the population expressing the remainder, either alone or in some alternative combination.
In claim 2, the phrase “pluripotent stem cell-derived” implies the method of claim 1 further requires an additional active step before the “providing” step of deriving cardiovascular progenitor cells from a pluripotent stem cell(s).
In claim 3, the term “cardiovascular mesoderm cell” is not defined by the instant application, but in view of the prior art, a cardiovascular mesoderm cell lineage can be phenotypically identified as Nkx2-5+ Isl1+ and often Mesp1+ Flk1+ or as Tbx5+ and Hand1+, as well as by further lacking neural crest markers (Sendra et al., J Cardiovasc Dev Dis 9: 5 (2021) at pg. 8-10).
In claims 9, 12 and 15, the phenotypes recited as a gene name followed by a plus sign (e.g., GATA4+) is interpreted to mean the cell comprises the named gene, e.g., GATA4, i.e., is positive for the presence of this gene.
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 1-3, 5, 7, 9, 12, and 15-16 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.
The claims are directed to methods of producing NKX2-5+ CD31+ endocardial cells wherein the method comprises the steps of (1) providing cardiovascular progenitor cells and (2) contacting these cells with FGF and BMP in a culture condition. The claims are broad in that no other active step is expressly recited or implied and yet the required NKX2-5+ CD31+ endocardial cell population must be generated. The claims are also broad in that the genus FGF encompasses any concentration of any FGF, with specific description for 5-100 ng/mL bFGF (FGF-2), and any concentration of any BMP, such as 3-100 ng/mL of BMP4 and/or BMP10 (see instant pg. 15, lines 14-16; FIG. 1).
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. In the instant case, the specification fails to provide any other representatives concentration species for the FGF genus and BMP genus other than those noted above (e.g., ranges) with working embodiments specifically using FGF-2 at 50 ng/mL and BMP10 at 10 ng/mL (Example 3).
The prior art teaches the FGF family encompasses various factors, including FGF19, FGF21 and FGF23 which act as hormones instead of growth factors (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 predictability. The FGF concentration guidance is based on a single representative species, FGF-2. The prior art also teaches the BMP family encompasses GDF5, GFD6 and GDF7 and that different BMPs have different activities: with BMP2/4/15 signaling through Alk3 and Alk6; BMP5-8 signaling through Alk2, Alk3, and Alk6; BMP9-10 signaling primarily through Alk1; and GFF5-7 signaling through Alk6 (Gipson et al., Bone 140: 115549 (2020) at pg. 3). Thus, not all BMPs are functionally equivalent with each other or be expected to function in the same manner in the concentration range described for two representative species, 3-20 ng/mL/
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 concentrations of FGFs and BMPs to ensure the predictable production of an NKX2-5+ CD31+ endocardial cell population by the claimed methods.
35 USC § 112(a), Scope of Enablement
Claims 1-3, 5, 7, 9, 12, and 15-16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because while enabling the method of claim 1 that further comprises culturing the cardiovascular cells for a sufficient duration under suitable cell physiological conditions, the specification does not enable any person, skilled in the art to which it pertains, or with which it is most nearly connected to, to produce a population of endocardial cells from cardiovascular progenitor cells merely by contacting the cardiovascular progenitor cells under culture conditions with both FGF and BMP.
Enablement is considered in view of the Wands factors (MPEP 2164.01 (a)). The court in Wands states that "Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is 'undue.' Not 'experimentation;" (Wands, 8 USPQ2d 104). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. "Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighting many factual considerations." (Wands, 8 USPQ2d 1404).
The factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation required is “undue” include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Furthermore, the 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. And thus, skepticism raised in the enablement rejections are those raised in the art by artisans of expertise.
All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Breadth of claims
The claims are directed to methods of producing NKX2-5+ CD31+ endocardial cells wherein the method comprises the steps of (1) providing cardiovascular progenitor cells and (2) contacting these cells with FGF and BMP in a culture condition. The claims are broad in that no other active step is expressly recited or implied and yet the required NKX2-5+ CD31+ endocardial cell population is generated by these two simple steps.
The state of the art:
The prior art teaches that cardiovascular progenitor cells can express Nkx2.5 and CD31 (Moretti et al., Cell 127: 1151-65 (2006), IDS ref.; at Fig. 3A, 4J, 6-7) and in vitro cardiovascular progenitor cells sometimes spontaneously produce Nkx2.5+ endocardial cells after 10 days of coculture on cardiac feeder cells (Moretti at pg. 1159; Fig. 5, 7I). The prior art also teaches FGF-2 signaling and BMP2/4 signaling can induce expression of Nkx2.5 and CD31 through a time-consuming mechanism requiring at least 1-2 hours via activating the PI3K/AKT, MAPK/ERK pathways and/or Smad phosphorylation, which alone takes at least 5-15 minutes.
Thus, the prior art is silent as to instantaneously converting cardiovascular progenitor cells into endocardial cells or by a culturing step without cardiac feeder cells or ECM or with exogenous FGF and/or BMP at duration less than 1 hour. These aspects of using must be shown to a reasonable extent so that one of the ordinary skills in the art would be able to practice the invention without any undue or unreasonable burden being on such artisan.
The amount of direction and guidance as well as any working examples provided:
The instant specification provides working examples of methods of differentiating pluripotent stem cells into cardiogenic mesodermal cells and then into NKX2-5+ CD31+ endocardial cells using a multiday culturing step in a medium comprising FGF-2 at 50 ng/mL and BMP10 at 10 ng/mL or lacking FGF-2 (Example 3, FIG 1-3).
Nowhere does the instant specification show how to perform this method in less than 6 days instead using a method comprising at least 2-3 culturing steps of culturing with FGF-2 for 2 or more days (day3-day5) and culturing with BMP10 for 4 days (day5-day9). Thus, there is no evidence in the instant application or the prior art that the scope of contacting encompassed by the claims could predictably result in a population of NKX2-5+ and CD31+ endocardial cells as recited in the claims.
Undue experimentation would be required to fill these gaps and unpredictability. Undue experimentation is required to differentiate cardiovascular progenitor cells with any FGF and any BMP in the absence of a coculture with cardiac cells. Undue experimentation is required to differentiate cardiovascular progenitor cells with any concentration of the FGF and BMP. Undue experimentation is required to differentiate cardiovascular progenitor cells instantaneously with FGF-2 and BMP-4/10.
In summary, the claims are rejected under 35 U.S.C. 112(a) because the specification does not reasonably provide enablement to a person skilled in the art to produce endocardial cells merely by contacting any cardiovascular progenitor cell population with any FGF and BMP at any concentration as recited in the claims. Given the lack of working examples, the limited guidance provided in the specification, the lack of guidance in the prior art, and the broad scope of the claims, undue and/or unreasonable experimentation would have been required for one skilled in the art to produce the recited result over the full 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 1-3, 5, 7, 9, 12, 15-16, and 24-25 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.
Claim 1 recites the phrase “under appropriate culture conditions” regarding the contacting of cardiovascular progenitor cells with FGF and BMP. A person of ordinary skill in the art reading the claim would not understand the metes and bounds of the “appropriate culture conditions” for contacting a cardiovascular progenitor cell with FGF and BMP as neither the claim nor the instant application provides any definition or standard for the term “appropriate” nor how “culture” conditions relate to the “contacting.” See MPEP 2173.05(b). For example, dependent claim 7 asserts appropriate conditions include the absence of VEGF or a Wnt inhibitor, however this is not clearly a negative definition. Is including VEGF and/or a Wnt inhibitor an inappropriate culture condition for “contacting” cardiovascular progenitor cells with FGF and BMP? Claims 2-3, 5, 7, 9, 12, 15-16, and 24-25 are included in this rejection for depending from indefinite claim 1.
In claims 9, 12 and 15, the symbology for phenotypes recited as a gene name followed by a plus sign (e.g., GATA4+) is not defined by the claims nor the instant application. However in view of the application, the term may be intended to encompass a positive RT-qPCR analysis of RNA expression in a cell (see instant FIGs 3-6 and 10 15). Therefore, the symbology is ambiguous and unclear as to whether the phenotype is for the positive presence of a gene and/or a gene product, such as its RNA or protein product(s). Claim 16 is included in this rejection for depending from indefinite claim 15. Note in claim 1, the terms NKX2-5+ or CD31+ are interpreted as ordinarily used in the art to mean the cells are positive either for the named protein (NKX2-5+ or CD31+) or an mRNA encoding it and as determined by an appropriate assay recognized by ones of ordinary skills in the art.
Claim 9 recites the term “ENG(CD105)+”, which is ambiguous and unclear as to whether the language in the parenthesis is a limitation or optional feature, namely whether the cell must be phenotypically positive for the ENG gene and the CD105 protein product thereof, or just the encoding ENG gene alone.
Claim 12 recites the relative term “like” with regard to a specific cell type (valvular interstitial-like cells (VICs)), but these cell types are not defined in the claims nor the instant specification, with only representative examples described. As the prior art does not provide a standard for measuring a requisite degree of “likeness”, a person of ordinary skill in the art would not understand the metes and bounds of the term “valvular interstitial-like cells.” “When a term of degree is used in the claim, the examiner should determine whether the specification provides some standard for measuring that degree” and if the specification does not provide some standard for measuring that degree, “a determination must be made as to whether one of ordinary skill in the art could nevertheless ascertain the scope of the claim (e.g., a standard that is recognized in the art for measuring the meaning of the term of degree). See MPEP 2173.05(b) (I). As “like” can mean a variety of deviations from actual valvular interstitial cells, a person of ordinary skill in the art would not be appraised of the metes and bounds of the scope of the claim term.
Claim 15 recites the term “MYL2(MLC2V)+”, which is ambiguous and unclear as to whether the language in the parenthesis is a limitation or optional feature, namely whether the cell must be phenotypically positive for the MYL2 gene and the MLC2V protein product thereof, or only the MYL2 gene encoding it.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 9 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 9 further limits the produced population of NKX2-5+ CD31+ endocardial cells of claim 1 to phenotypically being (1) GATA4+, GATA5+, NFATC1+, NPR3+ and NRG1+; or (2) ENG(CD105)+ without reciting or implying any limitation to the method of claim 1. Thus, absent evidence to the contrary, the result of performing the method of claim 1 inherently produces such cells. If it does not, then claim 9 fails to adequately describe all essential features of the invention of claim 9.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 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.
(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 1-3, 5, and 9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Misfeldt (Misfeldt et al., Dev Biol 333: 78-89 (2009), IDS ref.) as evidenced by EU330531 (GenBank Accession EU330531, NCBI (2016)).
Regarding claim 1, Misfeldt discloses culturing for 6-7 days in bFGF (30 ng/mL) and BMP4 (50 ng/mL) isolated mesodermal cardiovascular progenitor cells (E-cadherin+ Flk1+) to produce cell populations comprising Nkx2.5+ cardiomyocytes and CD31+ endocardial cells (pg. 84, left col., last para., to pg. 85, right col., last para; Fig. 6-7).
Regarding claim 2, Misfeldt discloses the progenitor cells are descended from pluripotent stem cells (embryonic stem cells (ESCs)) (pg. 84, left col., last para., to pg. 85, right col., last para; pg. 79, right col., 2nd para.).
Regarding claim 3, Misfeldt discloses the progenitor cells are mesodermal and cardiogenic, i.e., can differentiate into mesodermal cardiovascular cells, e.g., Nkx2.5+ isl1+ and often Flk1+ or Tbx5+ (pg. 84, left col., last para., to pg. 85, right col., last para; Fig. 6-7).
Regarding claim 5, Misfeldt discloses the BMP is BMP4 (pg. 85).
Regarding claim 9, Misfeldt discloses wherein the cells are derived from FVB mouse cells (pg. 79, left col., 1st para.; pg. 84, left col., last para., to pg. 85, right col., last para; Fig. 6-7). Although Misfeldt does not expressly disclose the resulting population of endocardial cells are ENG+ or GATA4+, GATA5+ NFATC+, NPR3+ and NRG1+ all nucleated FVB mouse cells inherently comprise these genes, e.g., ENG, as evidenced by EU330531. Thus, Misfeldt anticipates the claimed invention.
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 1-3 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Misfeldt.
The claims are interpreted as set forth in a previous section.
Misfeldt teaches a method of producing a population of cells comprising CD31+ and Nkx2.5+ endocardial cells from cardiovascular progenitor cells by culturing embryonic stem cells into embryoid bodies to day 8-11 (Fig. 3). Misfeldt teaches culturing mesodermal cardiovascular progenitor cells isolated from day 3-4 embryoid bodies on feeder cells for at least 6 days in media comprising bFGF and BMP4 to produce cell populations comprising Nkx2.5+ cardiomyocytes and CD31+ endocardial cells (Fig. 6-7; pg. 84, left col., last para., to pg. 85, right col., last para.).
As set forth above, Misfeldt anticipates claims 1-3 and 5, and thus, Misfeldt renders obvious the subject matter of claims 1-3, and 5. Thus, the claimed invention as a whole is prima facie obvious prior to the earliest effective filing date in the absence of evidence to the contrary.
Claims 1-3, 5 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Misfeldt as applied above, and further in view of EU330531.
As set forth above, Misfeldt as evidenced by EU330531 anticipates claim 9, and thus, Misfeldt in view of EU330531 renders obvious the subject matter of claims 1-3, 5, and 9. Thus, the claimed invention as a whole is prima facie obvious prior to the earliest effective filing date 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-2 and 5-7 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 12 and 25 of copending Application No. 17/922,731 (reference application) as evidenced by Misfeldt (Misfeldt et al., Dev Biol 333: 78-89 (2009)).
Although the claims at issue are not identical, they are not patentably distinct from each other because claims 12 and 25 of the reference application teach methods of culturing pluripotent stem cells into cardiomyocytes via first making embryoid bodies and culturing the cells of the embryoid bodies in a medium comprising BMP and FGF to generate cardiovascular mesoderm cells. As evidenced by Misfeldt, populations of cells derived from cardiovascular progenitor cells by culturing with exogenous BMP and FGF for at least 6 days comprise not only cardiomyocytes but also NKX2-5+ endocardial cells and CD31+ endocardial cells (pg. 83, right col; Fig. 4, pg. 84, left col., last para., to pg. 85, right col., last para; Fig. 6-7). Regarding instant claim 2, reference claim 12 teaches the cardiovascular progenitor cells are derived from pluripotent stem cells (hPSCs). Regarding instant claim 5, reference claims 12 and 25 teach wherein the BMP comprises BMP4. Regarding instant claim 6, reference claims 12 and 25 teach wherein the FGF is bFGF. Regarding instant claim 7, reference claim 12 never teaches including a VEGF or Wnt inhibitor.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERIC J ROGERS whose telephone number is (571)272-8338. The examiner can normally be reached Monday - Friday 9:00-6:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Tracy Vivlemore can be reached on (571) 272-2914. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ERIC J ROGERS/Examiner, Art Unit 1638
/KEVIN K HILL/Primary Examiner, Art Unit 1638