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 .
Priority
This application claims benefit to US provisional 63/484,677 (filed on 02/13/2023).
Information Disclosure Statement
IDS filed on 09/30/2024 contained two copies of the IDS form. As such, one of the forms has been crossed out and not considered.
Election/Restrictions
Applicants’ election without traverse of invention group I, drawn to a method for producing a population of RV-like cardiomyocytes from hPSCs; population of RV cardiomyocytes; and population of SHF progenitor cells, filed on 06/12/2026, is acknowledged.
Applicants also elected without traverse the species of insulin signaling activator as the additive to the method of producing a population RV-like cardiomyocytes, filed on 06/12/2026, is acknowledged.
Claims Status
Claims 1-37 are pending.
Claims 10-21 and 26-37 are withdrawn per invention and species election.
Claims 1-9 and 22-25 have been examined on the merits.
Claim Interpretation
For clarity of the record the following comments are made regarding claim interpretation under broadest reasonable interpretation:
None of the ‘optionally’ limitation are considered as required by the claims.
Claims 22-25 are product-by-process claims. Product-by-process limitations are considered only insofar as the method of production imparts distinct structural or chemical characteristics or properties to the product. Therefore if the product, as claimed, is the same or obvious over a product of the prior art (i.e. is not structurally or chemically distinct), the claim is considered unpatentable over the prior art, even though the prior art product is made by a different process. See MPEP 2113.
In the instant case, claim 22 is drawn to SHF cardiac progenitor cells made by steps a)-c) of claim 1. Claims 23-25 are drawn to a population of RV cardiomyocytes produced by the method of claim 1. The method of production for both cell populations requires the use of insulin signaling activator. The specification shows that inclusion of insulin signaling activator has appreciable effect on the phenotype of the SHF cardiac progenitor cells and RV cardiomyocytes (See, Example 6, Specification ¶00128, Fig 13).
Claim Rejections - 35 USC § 112
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.
Claims 23 and 24 are 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.
Claims 23 and 24 recite phenotypic properties of the RV cardiomyocytes that would be inherent in the cell population produced by the method of claim 1.
Applicant may cancel the claims, amend the claims to place the claims in proper dependent form, rewrite the claims in independent form, or present a sufficient showing that the dependent claims 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 (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.
Claims 1-9 and 22-25 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Braam et al (US2018/0251734 A1); evidenced by Kempf and Zweigerdt (Advances in biochemical engineering/biotechnology, 2018).
Braam et al disclosed a method of differentiating human pluripotent stem cells (hPSCs) into human stem cell-derived population of cardiomyocytes (See, Abstract).
Regarding claims 1 and 23, Braam et al disclosed a method of differentiating human stem cells into ventricular cardiomyocytes (See, ¶0033). This reads on, a method for producing a population of RV-like cardiomyocytes from hPSCs, of claim 1. Although Braam et al is silent on if the cardiomyocytes are right ventricular, as the active steps of the methods are the same, this would be an inherent property of the ventricular cardiomyocytes generated by the method of Braam et al.
Braam et al disclosed an in vitro method of culturing hPSCs into cardiomyocyte cell population comprising a) hPSC is contacted with a Wnt-signaling agonist in an aqueous media, such as CHIR 99021, this reads on, a method…comprising a)culturing hPSCs with a Gsk3 inhibitor to obtain a first population, as CHIR 99021 is Gsk3 inhibitor.
b) hPSC population is contacted with XAV-939, a Wnt/β-catenin signaling pathway inhibitor, this reads on, c) culturing the first population of cells with Wnt/β-catenin signaling pathway inhibitor to obtain second population of cells comprising SHF cardiac progenitor cells,
c) contacting the cell population with IGF1 and IGF2, this reads on, wherein an insulin signaling activator is added…,
and an optional step d) cells are cultured in an aqueous media for maturing the cardiomyocyte population without CHIR 99021, XAV939 and IWP-L6 (See, ¶ 0048-0128), this reads on, d)culturing second population of cells…without Wnt/β-catenin signaling pathway inhibitor to obtain a third population of cells, of claim 1.
The culturing of steps a) and b) of Braam et al results in progenitor cells population evidenced by Kempf and Zweigerdt. Figure 2 of Kempf and Zweigerdt teaches a time course of the cardiac differentiation protocol for hPSCs (See, Figure 2 p 43). Figure two shows that after induction of hPSCs with CHIR99021, the cells begin to differentiate into a new cell population comparative to primitive streak cells, treating the population with Wnt/β-catenin signaling inhibitors such as, IWP2/4, IWR-1, or XAV939, generates a population of cardiac progenitor cells, then insulin signaling activator, IGF-1 is used to expand the cell populations (See, figure 2 p43). Therefore, the method of Braam et al also reads on, SHF cardiac progenitor cells because the method of Braam et al comprise the same active steps of the instant application, while Braam et al and Kempf and Zweigerdt are silent on the specific subtype of cardiac progenitor cell generated, this characteristic would be inherent to the population generated by the method of Braam et al.
Braam et al disclosed that the IGF (IGF1 and IGF2) can be added at any stage of the differentiation method, as it does not negatively impact the method; it can be added before step a) or b) or after step b) (See, ¶0081). This reads on, wherein an insulin signaling activator is added anytime between step (a) and step (b).
The cell population produced by the method of Braam et al reads on population comprising RV cardiomyocytes produced by the method of claim 1, of claim 23.
Regarding claim 2, following the discussion above, Braam et al disclosed that the media with the insulin signaling activator (IGF) is in medium C, which is contacted with the cell population for at least 1 day or 1-35 days (See, ¶0113). This reads on, wherein the insulin signaling activator is present in culture media for 24 to 48 hours.
Regarding claim 3, following the discussion above, Braam et al disclosed that the IGF (IGF1 and IGF2) can be added at any stage of the differentiation method (See, ¶0081). This reads on, wherein the insulin signaling activator is…IGF-1.
Regarding claim 4, following the discussion above, Braam et al disclosed that the Wnt signaling agonist is preferably CHIR 99021 used in the method, which is also a Gsk3 inhibitor (See, ¶0066-0075). This reads on, wherein the Gsk3 inhibitor is CHIR 99021.
Regarding claim 5, following the discussion above, Braam et al disclosed that XAV939 is a β-catenin inhibitor used in the method (See, ¶0056). This reads on, wherein the Wnt/β-catenin signaling pathway inhibitor is XAV939.
Regarding claim 6, following the discussion above, Braam et al disclosed a method that comprises IGF-1 in the differentiation. Kempf and Zweigerdt teaches that IGF-1 has been shown to enhance the expansion of cardiovascular progenitors (CVP) but not differentiated hPSC-cardiomyocytes at later stages during hPSC to cardiomyocyte differentiation (See, p44 paragraph 3, Figure 2).
As Braam et al disclosed a method that anticipates the method of claim 1, and as Kempf and Zweigerdt evidences IGF-1 enhances the progenitor population, Braam et al implicitly teaches a cell population that reads on the instant claim 6.
Regarding claim 7, following the discussion above, Figure 2 of Braam et al shows hPSCs differentiated for 2 days with CHIR99021, then XAV939 for 2 days, then in differentiation media for 10 days, has approximately 60% of cardiomyocytes with XAV939 and IWP-L6 (See, ¶0167 and Figure 2). This reads on, wherein the RC cardiomyocytes are between 60% and 80% of the third population of cells without cell separation.
Regarding claims 8-9 and 24-25, following the discussion above, the ventricular cardiomyocytes produced by the method of Braam et al has the same active steps as the instant application, therefore, the cardiomyocytes of Braam et al would inherently have the properties in the claims. Therefore, the ventricular cardiomyocytes of Braam et al would have distinct properties such as, sarcomere formation, cell size, spontaneous contraction rate, Ca2+ transient event duration, contraction speed, and relaxation speed.
Regarding claim 22, following the discussion above, the method of Braam et al reads on, SHF cardiac progenitor cells because the method of Braam et al comprise the same active steps of the instant application, while Braam et al and Kempf and Zweigerdt are silent on the specific subtype of cardiac progenitor cell generated, this characteristic would be inherent to the population generated by the method of Braam et al. Therefore, the population is produced and this reads on, a population comprising SHF cardiac progenitor cells produced by step a) to step c) of the method claim 1.
Therefore claims 1-9 and 22-25 are anticipated by Braam et al and evidenced by Kempf and Zweigerdt.
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 and 5 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1,2,3,4, and 12 of U.S. Patent No. 11,136,551 B2 in view of Kempf and Zweigerdt (Advances in biochemical engineering/biotechnology, 2018).
The teachings of Kempf and Zweigerdt are set forth above.
Regarding claim 1, reference patent claim 1 recites, an in vitro method for use in differentiating a human pluripotent stem cell population into a cardiomyocyte cell population, comprising a) contacting the hPSC population with XAV-939 and IWP-L6 in an aqueous media. Reference patent claim 2 recites, wherein the method further comprises b)contacting, prior to step a) the hPSC population with at least a Wnt-signaling agonist in an aqueous media. Reference patent claim 3 recites, wherein the method further comprises contacting the hPSC population with IGF. Reference patent claim 4 recites, wherein the method further comprises c) contacting after step a) hPSC population with aqueous media devoid of XAV-939, IWP-L6, and said Wnt signaling agonist. This all reads on steps a) – d) of instant claim 1 and the scope of the claim because the Wnt signaling agonist is a Gsk-3 inhibitor. While the reference patent claims is silent when the IGF or the insulin signaling is added during the method, Kempf and Zweigerdt provide motivation to add it during the progenitor stage expansion of the method.
Regarding claim 5, reference patent claim 1 recites that the hPSCs are contacted with XAV-939, which is a Wnt/β catenin signaling pathway inhibitor. This reads on instant claim 5.
Therefore, instant claims 1 and 5 are rendered obvious over U.S. Patent No. 11,136,551 B2 in view of Kempf and Zweigerdt (Advances in biochemical engineering/biotechnology, 2018).
Claims 1,4,5, and 7 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1,2,3,9,17, and 18 of U.S. Patent No. 8,951,798 B2 in view of Braam et al (US2018/0251734 A1) and Kempf and Zweigerdt (Advances in biochemical engineering/biotechnology, 2018).
The teachings of Braam et al and Kempf and Zweigerdt are set forth above.
Regarding claims 1, reference patent claim 18 recite, a method for generating human cardiomyocytes, comprising, sequentially inhibiting Gsk-3 in the hPSCs and then inhibiting Wnt signaling in the Gsk-3 inhibited cells; and culturing the sequentially inhibited cells in a culture medium to form a differentiated cell population comprising cardiomyocytes, wherein the culturing is free of exogenous growth factors. This reads on the active steps of instant claim 1. Reference patent claim 1 recites that the activating Wnt/β catenin signaling in hPSCs by inhibiting Gsk-3 to obtain a first population of cells, then inactivating Wnt/β catenin signaling with an inhibitor, indicating that a progenitor population is produced in the active steps of reference patent claim 18.
Reference patent claims is silent on the addition of IGF-1 to the method of culturing hPSCs to cardiomyocytes but Braam et al and Kempf and Zweigerdt provide motivation and evidenced success in adding IGF-1 to the method for improved results during the progenitor expansion stage.
Regarding claims 4, following the discussion above, reference patent claims 2 and 3 recite, wherein the inhibiting Gsk-3…. CHIR 99021.
Regarding claim 5, following the discussion above, reference patent claim 9 recites, wherein the small that stimulates β catenin degradation is XAV-939, thus inhibiting Wnt/β catenin signaling. This reads on instant claim 5.
Regarding claim 7, following the discussion above, reference patent claim 17 recites, wherein the culturing steps comprises culturing in RPMI base medium, wherein at least 70% of the cells in the cell population comprising cardiomyocytes…, wherein no cell separation or selection step was used. This reads on the instant claim.
Therefore, claims 1,4,5, and 7 are rendered obvious by U.S. Patent No. 8,951,798 B2 in view of Braam et al (US2018/0251734 A1) and Kempf and Zweigerdt (Advances in biochemical engineering/biotechnology, 2018).
Claims 1,4,5, and 7 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1,4,9,18,19, and 20 of U.S. Patent No. 9,453,201 B2 in view of Braam et al (US2018/0251734 A1) and Kempf and Zweigerdt (Advances in biochemical engineering/biotechnology, 2018).
The teachings of Braam et al and Kempf and Zweigerdt are set forth above.
Regarding claim 1, reference patent claim 1 recites, a method for generating a cell population of human cardiomyocyte progenitors, comprising inhibiting Wnt/β catenin signaling in the first cell population to obtain a second cell population, comprising cardio myocyte progenitors, wherein inhibiting comprises culturing the first cell population in the presence of an inhibitor of Wnt/β catenin signaling,…, wherein the first cell population is obtained by activating Wnt/β catenin signaling in hPSCs by culturing the hPSCs in the presence of Gsk-3 inhibitor. Reference claim 19 recites, further comprising culturing the second cell population in the substantial absences of exogenous growth factors after ending the inhibition of Wnt/β catenin signaling to obtain a cell population comprising cardiomyocytes.
Reference patent claims is silent on the addition of IGF-1 to the method of culturing hPSCs to cardiomyocytes but Braam et al and Kempf and Zweigerdt provide motivation and evidenced success in adding IGF-1 to the method for improved results during the progenitor expansion stage.
Regarding claim 4, reference patent claim 4 recites, wherein the GSk-3 inhibitor is a small molecule…. CHIR99021. This reads on instant claim 4.
Regarding claim 5, reference patent claim 9 recites, wherein the small molecule that inhibits Wnt/β catenin signaling is… XAV939. This reads on claim 5.
Regarding claim 7, reference patent claim 20 recites, wherein the cell population comprising at least 70% cTnT-positive cells is obtained without cell separation or selection step. This reads on instant claim 7.
Therefore, claims 1,4,5, and 7 are rendered obvious over U.S. Patent No. 9,453,201 B2 in view of Braam et al (US2018/0251734 A1) and Kempf and Zweigerdt (Advances in biochemical engineering/biotechnology, 2018).
Claims 1,4,5, and 7 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1,2,6,11,20, and 21 of U.S. Patent No. 9,663,764 B2 in view of Braam et al (US2018/0251734 A1) and Kempf and Zweigerdt (Advances in biochemical engineering/biotechnology, 2018).
The teachings of Braam et al and Kempf and Zweigerdt are set forth above.
Regarding claim 1, reference patent claim 1 recites, a method for generating a cell population of human cardiomyocytes, comprising inhibiting Wnt/β catenin signaling in a first cell population to obtain a second cell population comprising cardiomyocyte progenitors, wherein the first cell population is obtained by activating Wnt/β catenin signaling in hPSCs; and culturing in a medium….after ending the inhibition of Wnt/β catenin signaling to obtain a cell population comprising human cardiomyocytes. This reads on the active steps of instant claim 1 a)-d).
Reference patent claims is silent on the addition of IGF-1 to the method of culturing hPSCs to cardiomyocytes but Braam et al and Kempf and Zweigerdt provide motivation and evidenced success in adding IGF-1 to the method for improved results during the progenitor expansion stage.
Reference patent claims 20 and 21 have a scope of invention that also reads on instant claim 1 based on the active steps, in view of Braam et al and Kempf and Zweigerdt.
Regarding claim 4, following the discussion above, reference claim 6 recites, wherein the Gsk-3 inhibitor is a small molecule…CHIR 99021. This reads on instant claim 4.
Regarding claim 5, following the discussion above, reference claim 11 recites, wherein the small molecule that inhibits Wnt/β catenin signaling is…XAV939. This reads on instant claim 5.
Regarding claim 7, following the discussion above, reference claims 2 and 21 recite, wherein the cell population comprises at least 70% cTnT-positive cells and is obtained without a cell separation or selection step. This read on instant claim 7.
Therefore, instant claims 1,4,5, and 7 are rendered obvious over U.S. Patent No. 9,663,764 B2 in view of Braam et al (US2018/0251734 A1) and Kempf and Zweigerdt (Advances in biochemical engineering/biotechnology, 2018).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Caroline M Lara whose telephone number is (571)272-4262. The examiner can normally be reached 7:00 to 4:30pm M-Th.
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/CAROLINE M LARA/Examiner, Art Unit 1633 /ALLISON M FOX/Primary Examiner, Art Unit 1633
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