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 .
Claims 1-16 are pending as originally filed and are considered herein.
Specification
The specification is objected to. Page 42 and page 70, in table 3, discloses sequences requiring sequence identifiers. See attached PTO-2301
Claim Objections
Claim 2 is objected to because of the following informalities: Claim 2 identifies "CD172a" and "CD172". It is clear that Applicant means "CD172a" in each instance. Appropriate correction is required.
Applicant is advised that should claim 4 be found allowable, claim 5 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). Claim 5 differs from Claim 4, in that it is proclaims itself to be a method of determining if a dose of PSC-CM is likely to cause arrhythmia upon transplant, but utilizes the same step as Claim 4, even to the point of referring to Claim 4 for such step. The sole difference is whether you are determining if arrhythmogenic PSC-CM is present, or whether it causes arrhythmia. The realization is not a measurable quantity, as it exists in the mind of the Artisan, not as a physical characteristic. Thus, these two claims have substantially the same scope.
Applicant is advised that should claim 2 be found allowable, claims 6 and 7 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). Claim 2 requires the steps of providing the PSC-CM population, determining if CD200 is present on the cell surface of at least some cells in the population, and removing the PSC-CM that are CD200+ from the population. (I.e., the “optionally” steps are not required of the claim, as they are optional.) Claim 6 requires eliminating or reducing arrhythmia following transplant of a dose of PSC-CM, but explicitly requires the method be performed before administration. The seps include identifying if arrhythmogenic PSC-CM are present, via Clim 4, which is the determination of CD200 on some portion of the cells of PSC-CM, then removing the arrhythmogenic PSC-CM from the dose. This is necessarily a removal of CD200+ cells, as implied by determining the CD200+ cells, as well as the arrythmic cells being CD200+. Thus, despite distinct proposed purposes and realizations, the steps and structure of these claims substantially the same. With regard to Claim 7, the method states a purpose of providing PSC-CM substantially free of arrhythmogenic PSC-CM, with the same steps as Claim 6. Thus, again the structure of the claim is identical to Claims 2 and 6.
Applicant is advised that should claim 4 be found allowable, claim 8 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). Claim 4 identifies an arrhythmogenic PSC-CM cell, by determining if CD200+ is expressed on the cell surface, and if it is so-expressed, it is an arrhythmogenic PSC-CM. Claim 8 differs in identifying a PSC-PM, by determining if CD200 is similarly expressed, and if it is, it is a PSC-PM. Looking to the specification, these cells are derived from the same population originally, i.e., paragraphs 124 and 155 of the Application publication 2026/0158074. Thus, the difference in these claims is the particular realization that CD200+ are both PSC-CM and PSC-PM, which is not a measurable quantity, but a realization. Therefore, despite a slight difference in wording, these claims have substantially the same scope.
Applicant is advised that should claims 2, 6, and 7 be found allowable, claim 9 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). Similar to the reasoning above for the distinction between Claims 4 and 8, Claim 9 is related to Claims 2, 6, and 7, through the label PSC-CM and PSC-PM, but the structure of the steps is identical between Claims 9 and Claims 2, 6, and 7. However, Claim 7 removes implies the keeping of CD200+ cells, while claims 2 and 6 imply the keeping of the CD200- cells. However, the separation occurs in either case. Thus the distinctions are simply realizations, and that is not a measurable property. Thus, these claims have substantially the same scope.
Applicant is advised that should claims 4 and 5 be found allowable, claim 10 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). Claim 10 teaches identifying PSC-VM, by the presence of CD200 on th surface of the iPSC derived cardiac cell. As seen by paragraph 124 of the specification publication 2026/0158074, these are the same pool of cells in the claims, and the steps are the same. The distinct is the realization, which is not measurable. Thus, despite a slight distinction in wording, these claims have substantially the same scope.
Applicant is advised that should claim 2, 6, 7, and 9 be found allowable, claim 11 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). In similar logic to that between 2, 6, 7, and 9 being substantially identical, Claim 11 isolates the CD200+ cells, which yields the isolation of CD200- from CD200+ cells, thereby providing the same scope, the distinction only being the realization of a property of the particular cell intended to be kept. The realization is not a measurable property, and thus, the structure of the claims is identical. Therefore despite a slight difference in wording, these claims have substantially the same scope.
Applicant is advised that should claim 12 be found allowable, claim 13 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). Claims 12 and 13 contain the same structure, the distinction being only realization lowered arrhythmia or free of arrhythmogenic PSC-CMs. The realization is not measurable, and thus, these claims have substantially the same scope.
Claim Rejections - 35 USC § 112
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.
Claim 12 is 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 12 provides an intent to reduce arrhythmia post-transplant, but there is no transplant, which precludes actually a reducing chance of arrhythmia. The Artisan would not know if the claim is complete, or requires more steps.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 4-5 rejected under 35 U.S.C. 101 because the claimed invention is directed to a law of nature without significantly more. The claim(s) recite(s) “if CD200 is expressed on the surface of the PSC-CM, the PSC-CM is an arrhythmogenic PSC-CM” and “if the dose contains arrhythmogenic PSC-CMs, the dose is likely to cause arrhythmia upon transplantation”. This judicial exception is not integrated into a practical application because it is merely an instruction to understand the realization in each case. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional elements, i.e., determining whether CD200 is expressed (i) occurs before the realization; and (ii) is one of the basic tools of science: identifying cell markers on cells.
Claims 6-7 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a law of nature without significantly more. The claim(s) recite(s) “eliminating or reducing arrhythmia following transplantation of a dose containing a plurality of PSC-CMs in a subject” and “providing a dose containing a plurality of PSC-CM which is substantially free of arrhythmogenic PSC-CMs”. This judicial exception is not integrated into a practical application because the claims are merely an instruction to realize the relationships. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional step of removing arrhythmogenic PSC-CMs is one of the basic tools of science: isolating populations of single cell types.
Claims 8 and 10 are rejected under 35 U.S.C. 101 because the claimed invention is directed to laws of nature without significantly more. The claim(s) recite(s) “identifying … (PSC-PM)” and “identifying … (PSC-VM)”. This judicial exception is not integrated into a practical application because it is merely an instruction to realize the relationship in each case . The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because (i) the step of identifying occurs before the realization and (ii) the identification of markers on a cell is one of the basic tools of science to characterize cells.
Claims 9 and 11 are rejected under 35 U.S.C. 101 because the claimed invention is directed to laws of nature without significantly more. The claim(s) recite(s) “providing a substantially pure dose of PSC-PM” or “providing a substantially pure dose of PSC-VM” due to the presence of CD200 in each case. This judicial exception is not integrated into a practical application because the identification is merely an instruction to realize the relationship in each case, being PSC-PM or PSC-VM. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because (i) determining step occurs before any realization takes place, and (ii) the isolating step is the basic tools of science: purification of single cell types.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-2 and 4-11 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Veevers, et al. (2018) “Cell-Surface Marker Signature for Enrichment of Ventricular Cardiomyocytes Derived from Human Embryonic Stem Cells”, Stem Cell Reports, 11: 828-24.
Claims 1-2: Veevers teaches identification and isolation of a CD200- cell population from hESC-derived VCMs (p. 833).
Claims 4-11: Veevers teaches idenfication and isolation of CD200+ cell population from the hESC-derived VCMs (pp. 833-34).
Further, it is noted in each case (the CD200- and CD200+ isolations) the isolation causes each to be isolated from the other, and thus, in each case they apply to all of Claims 1-2 and 4-11.
Claim Rejections - 35 USC § 112
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 15 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nakamura, et al. (2021 Oct 12) “Pharmacologic therapy for engraftment arrhythmia induced by transplantation of human cardiomyocytes”, Stem Cell Reports, 16: 2473-87.
Claim 15: Nakamura teaches administration of amiodarone and ivabradine administered to subjects that have engraftment arrhythmia (e.g., ABSTRACT, Figure 1, and p. 2477).
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 16 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Romagnuolo, et al. (2019) “Human Embryonic Stem Cell-Derived Cardiomyocytes Regnerate the Infarcted Pig Heart but Induce Ventricular Tachyarrhythmias”, Stem Cell Reports, 12: 967-87.
Claim 16: Romagnuolo teaches catheter ablation of engrafted hESC-CM graft recipients (e.g., p. 978, col. 1, paragraph 1).
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.
Claim 1 is 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.
Claim 1, when compared with Claim 2, indicates that Claim 1 can be obtained from other methods other than the growth and selection steps of Claim 2.
The specification is written in open-ended language indicating the same (e.g., page 81 of the specification). However, the only showing is the standard method of growing the cells from PSCs, and selection by way of the marker (e.g., paragraph 211 and 220).
The Art fails to provide another method of obtaining these, but it does demonstrate the ability to screen out with CD200 (e.g., Veevers, et al. (2018) “Cell-Surface Marker Signature for Enrichment of Ventricular Cardiomyocytes Derived from Human Embryonic Stem Cells”, Stem Cell Reports, 11: 828-24).
Given the great many possible conditions to make the PSC-CM that does not express CD200 from PSCs, and limited showing by Applicant and the Art, the Artisan would not have understood Applicant to have been in possession of the invention as claimed.
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 12-13 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.
Claims 12-13 are generic for providing PSC-CMs where they are grown in conditions that reduce the prevalence of arrhythmogenic PSC-CMs (i.e., those that express CD200 on the surface).
The specification provides antecedent basis for the same (e.g., paragraph 53). Moreover, description is provided by way of example, in the use of retinoic acid to activate the pathways for retinoic acid in pluripotent stem cells from days 2-6 of culturing (e.g., paragraph 221), in the standard protocol Applicant utilized (e.g., paragraph 237). This is in the context that current cardiac differentiation protocols yield heterogeneous cellular output populations (e.g., paragraph 88).
The Art at the time of invention generally recognized the difficulty in developing protocols to enrich for distinct cell types, including a lack of marker knowledge (e.g., Veevers, et al. (2018) “Cell-Surface Marker Signature for Enrichment of Ventricular Cardiomyocytes Derived from Human Embryonic Stem Cells”, Stem Cell Reports, 11: 828-24, p. 828, paragraph bridging columns). Through such methods, Veevers developed a protocol to enrich for cardiomyocytes that are CD77+/CD200- (e.g., Id.).
Thus, given the single showing of the use of retinoic acid in normal CM differentiation from pluripotent stem cells, the Artisan would not know what other compounds and/or in combination with what other medias and methods, could be used to obtain the same reduced levels of arrhythmogenic PSC-CMs, from PSCs.
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.
Claim 14 is 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.
Claim 14 is generic to the conditions of culturing PSCs effective to increase PSC-CM that do not express CD200 on their surface.
CD200- cells are taught to be non-arrhythmogenic CMs that have been isolated by Applicant from a standard cardiac differentiation protocol from PSCs. Thus, they are referred to as PSC-CMs that are CD200- (e.g., paragraph 88).
In the specification is described that the use of RA at days 2-6 of their protocol increases the prevalence of CD200+ cells (e.g., p. 62), and in view of that, the original protocol Applicant has utilized for differentiation of CMs would be considered to produce less CD200+ cells, thereby theoretically increasing CD200- CM cells, but that is not axiomatic, as it is also recognized that exist several cell types in the mixture (e.g., p. 62). Moreover, one of these must be the standard against which “increased” or “decreased” amounts is produced, and the whole the specification teaches that the “increase” is relative to the original differentiation protocol utilized (e.g., pp. 61-63). Thus, the Artisan left to find out what compounds would increase CD200- cell population size, versus the original protocol utilized.
The Art at the time of invention generally recognized the difficulty in developing protocols to enrich for distinct cell types, including a lack of marker knowledge (e.g., Veevers, et al. (2018) “Cell-Surface Marker Signature for Enrichment of Ventricular Cardiomyocytes Derived from Human Embryonic Stem Cells”, Stem Cell Reports, 11: 828-24, p. 828, paragraph bridging columns). Through such methods, Veevers developed a protocol to enrich for cardiomyocytes that are CD77+/CD200- (e.g., Id.). However, Veevers protocol did not change the proportion of these cells, but instead, purified out these CD200- cells.
Thus, give the broad range of molecules which may have an influence on increasing this population of cells in the protocol, and lack of description of a single molecule that does so, and recognition in the art that the markers and metabolism of the cells present is not even well characterized, The Artisan would not have understood Applicant to have been in possession of the invention as claimed.
Allowable Subject Matter
Claim 3 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of base claim 2 and any intervening claims.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT M KELLY whose telephone number is (571)272-0729. The examiner can normally be reached M-F: 8a-5p.
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ROBERT M. KELLY
Examiner
Art Unit 1638
/ROBERT M KELLY/Primary Examiner, Art Unit 1638
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