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
The instant application is Divisional of U.S. Application No. 16/333,549 (filed 03/14/2019; corresponding to U.S. Patent No. 11,591,570), which was a national stage entry under 35 U.S.C. § 371 of PCT/CA2017/051076 (filed 09/13/2017). Acknowledgement is made of Applicants’ claim for benefit of U.S. Provisional Application No. 62/395,371 (filed 09/15/2016).
Election/Restrictions
Applicant’s election without traverse of Group II (claims 12-27) in the reply filed on 12/18/2025 in response to a Restriction requirement is acknowledged.
Claims 1-28 were previously pending. Claims 1-11, 13, 18, 25, and 28 have been cancelled. Pending claims 12, 14-17, 20-24, and 26-28 read on the elected invention and are examined on the merits herein.
Information Disclosure Statement
The information disclosure statement filed 11/20/2023 fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. It has been placed in the application file, but the information referred to therein has not been considered in its entirety.
References lined through by the Examiner do not have a corresponding copy and, accordingly, have not been considered.
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 19-20 and 27 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 claims under rejection are directed to recombinant cardiomyocytes derived from the cell line designated hMYO-hERG (ATCC Designation No. PTA-123324). The issue at present is the scope of derivatives of said cell line covered by the claims. In giving the terms derived from or derivatives of their broadest reasonable interpretation, the number and types of cells which can be considered derivatives of the hMYO-hERG cell lines is extraordinarily great. The specification of the instant application discloses the generation of the hMYO-hERG cell line, wherein pseudovirus particles containing an expression vector expressing a C-terminal FLAG-tagged hERG were used to transduce adult human ventricular cardiomyocytes (par. 00187). A person having ordinary skill in the art may further transduce these cardiomyocytes with any number of genes to alter these cells. For example, Zhou, et al. teaches HEK 293 cells transiently and stably transfected with loss-of-function hERG mutations, e.g., I593R, Y611H, and G628S mutants (pg. 21062; col. 2, par 1. J Biol Chem. 1998). If one skilled in the art further transduced cells from the hMYO-hERG line with the mutants taught by Zhou, et al., these cells would be derivatives of the hMYO-hERG cell line and therefore encompassed by the scope of the claims under rejection. Alternatively, Zhang, et al. teaches the dedifferentiation of cardiomyocytes (PLoS ONE. 2010). Purified cardiomyocytes were cultured on grid-marked coverslips continuously in mitogen-rich medium for observation, wherein the cells flattened and lost their striations; the inward rectifier potassium current virtually disappeared, resting membrane potential became depolarized, and some cells no longer expressed myofilament cardiac troponin T (pg. 2; par. 3. Figs. 1, 2, 3A). If one skilled in the art dedifferentiated cells from the hMYO-hERG line as taught by Zhang, et al., these cells would be also be derivatives of the hMYO-hERG cell line and therefore encompassed by the scope of the claims under rejection. Thus, derivatives of the hMYO-hERG cell line is a genus of molecules.
To satisfy the written description aspect of 35 U.S.C. 112(a) for a claimed genus of molecules (or in this case, cells), it must be clear that: (1) the identifying characteristics of the claimed molecules (cells) have been disclosed, e.g., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed cor-relation between function and structure, or by a com-bination of such identifying characteristics; or (2) a representative number of species within the genus must be disclosed. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
While Applicants’ claims cover the full genus of derivatives of the hMYO-hERG cell line, Applicants’ disclosure thereof is limited to cells from the hMYO-hERG ATCC Designation No. PTA-123324 cell line, per se.
Regarding (1): A review of the specification fails to provide a definition of what structural characteristics the derivatives encompassed by the current claims must have. Applicants have not identified any particular core chemical structure or function (along with a correlation between function and a specific conserved structure) which must be shared by derivatives of the hMYO-hERG cell line; thus, one of ordinary skill in the art would not immediately envisage all derivatives of the hMYO-hERG cell line, as currently claimed. Therefore Applicants have not disclosed the identifying characteristics of the claimed cells.
(The Examiner acknowledges the specification does provide a definition of the term derivative in par. 0041; however, and as set forth above, this definition fails to identify the structural characteristics or correlation of between function and a specific structure necessary to satisfy the disclosure of identifying characteristics.)
Regarding (2): A review of the specification shows that Applicants have disclosed cells from the hMYO-hERG cell line and progeny thereof, per se, but no specific species of derivatives thereof. Disclosure of a single species does not constitute a representative number for such a broad genus as is encompassed by the breadth of ‘derivatives of the hMYO-hERG cell line’. Therefore Applicants have not disclosed a representative number of species, as would be required to support description and to show possession of the entire genus.
Thus, one of ordinary skill in the art, in looking to the instant specification, would not be able to determine that Applicants were in possession of the invention, as claimed, at the time the invention was made. Accordingly, the claims are considered to lack sufficient written description and are properly rejected under 35 USC 112(a).
Claims 19-20 and 26-27 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The invention appears to employ novel biological materials, specifically recombinant cardiomyocytes derived from the cell line designated hMYO-hERG (ATCC Designation No. PTA-123324). Since the biological material is essential to the claimed invention it must be obtainable by a repeatable method set forth in the specification or otherwise readily available to the public. If it is not so obtainable or available, the requirements of 35 USC 112(a) or pre-AIA 35 USC 112, first paragraph, may be satisfied by a deposit of the cell line.
It is noted that Applicants have deposited biological material at American Type Culture Collection (ATCC) under ATCC Designation No. PTA-123324, but there is no indication in the specification as to the public availability. If the deposit was made and accepted under the Budapest Treaty, then an affidavit or declaration by Applicant, or a statement by the attorney of record over his/her signature and registration number, stating such is required. To satisfy the deposit requirement made herein, the affidavit, declaration, or statement must state that the specific cell line has been deposited and accepted under the Budapest Treaty and that they will be available to the public under the conditions specified in 37 CFR 1.808.
If the deposit has NOT been made under the Budapest Treaty, then in order to certify that the deposit meets the criteria set forth in 37 CFR 1.80-1.809, applicants may provide assurance or compliance by an affidavit or declaration, or by a statement by an attorney of record over their signature and registration number showing that:
(a) during the pendency of this application, access to the invention will be afforded to the Commissioner upon request;
(b) upon granting of the patent the cell line will be available to the public under the conditions specified in 37 CFR 1.808;
(c) the deposit will be maintained in a public depository for a period of 30 years or 5 years after the last request or for the effective life of the patent, whichever is longer;
(d) a test of the validity of the biological material at the time of the deposit will be made (See 37 CFR 1.807); and
(e) the deposit will be replaced if it should ever become inviable.
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.
Claims 12, 14, 19-21, and 27 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.
Regarding claims 12, 14, 21: These instant claims are directed to different methods comprising the use of a recombinant cell line comprising recombinant cardiomyocytes stably expressing hERG. While these claims provide for the use of said recombinant cell line, the claims do not set forth any steps involved in the actual method; thus, it is unclear what method or process Applicants are intending to encompass.
A claim is indefinite where it merely recites a use without any active, positive steps delimiting how this use is actually practiced; see MPEP 2173.05(q). Therefore, claims 12, 14, and 21 are rejected for indefiniteness.
Regarding claims 19-20, 27: For the same reasons set forth above in the rejection of the instant claims for failing to comply with the written description requirement, the metes and bounds of these claims are not clearly or precisely defined. It would not be immediately understood by a person having ordinary skill in the art what cells are encompassed by derivatives of the hMYO-hERG cell line; thus, claims 19, 20, and 21 are rejected for indefiniteness.
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.
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 12 and 14-17 are rejected under 35 U.S.C. 103 as being unpatentable over Houghton, et al. (US 2015/0193575), in view of Teng, et al. (Cardiovasc Res. 2004).
Houghton, et al. teaches systems and methods for selecting compounds that have reduced risk of cardiotoxicity (Abstract).
Teng, et al. teaches repolarization activity in stem cell-derived cardiomyocytes overexpressing hERG N629D (Abstract).
Regarding claims 12, 14-17: Houghton, et al. teaches biological methods for testing the cardiotoxicity of a compound in an in vitro biological assay (par. 0032), such as a Cloe Screen IC50 hERG1 Safety assay (par. 0033). Houghton, et al. teaches the Cloe Screen IC50 hERG Safety assay measures whole-cell current from multiple cells simultaneously using an automated patch clamp system (par. 0300). CHO-hERG cells are dispensed into a PatchPlate, with amphotericin used as a perforating agent to gain electrical access to the cells; the hERG tail current is measured prior to the addition of a test compound by perforated patch clamping, and measured again after the test compound is added; post-compound hERG currents are expressed as a percentage of pre-compound hERG currents (par. 0301).
The Cloe Screen IC50 hERG Safety assay disclosed by Houghton, et al. reads on the method for determining cardiotoxicity of a compound or screening a compound for hERG inhibitory activity limitation recited in claim 12, the method for determining the activity of a compound to inhibit hERG limitation recited in claim 14, the limitations recited in steps b), c), and d) of claim 15, the wherein the test current is measured with electrophysiology techniques limitation recited in claim 16, and the wherein the test current is measured with a patch clamp apparatus limitation recited in claim 17.
Houghton, et al. does not teach the recombinant cardiomyocytes stably expressing or overexpressing hERG limitation recited in these claims.
However, Teng, et al. teaches embryonic stem cell-derived cardiomyocytes overexpressing N629D (pg. 270; col. 1, par. 1), a hERG1 mutation (pg. 268; col. 2, par. 1). Under broadest reasonable interpretation, the term stably expressing hERG recited in claims 12 and 14 is interpreted as any level of expression of hERG, and does not necessarily exclude overexpression of hERG. Therefore, the N629D-overexpressing cardiomyocytes of Teng, et al. read on the recombinant cardiomyocytes stably expressing hERG limitations recited in claims 12 and 14, as well as the recombinant cardiomyocytes overexpressing hERG limitation recited in step a) of claim 15.
It would have been prima facie obvious to a person having ordinary skill in the art to have modified the method of Houghton, et al. by substituting the CHO-hERG cells with the N629D-overexpressing cardiomyocytes of Teng, et al. This conclusion of obviousness is based on the ‘substitution rationale’. The use of the N629D-overexpressing cardiomyocytes in place of the CHO-hERG cells is a predictable use of prior art elements according to their established functions as cells which express hERG, leading to the predictable result of determining hERG inhibition of a test compound in hERG-expressing cells. This rationale aligns with the principle of a simple substitution of one known element for another to obtain predictable results; see MPEP 2143(I)(B). Therefore, claims 12 and 14-17 are rendered obvious over Houghton, et al., in view of Teng, et al.
Claims 21-24 are rejected under 35 U.S.C. 103 as being unpatentable over Benjahad, et al. (WO 2015/144614), in view of Teng, et al. (Cardiovasc Res. 2004).
Benjahad, et al. teaches diazaspiroalkanone-substituted oxazole derivatives that selectively modulate, regulate, and/or inhibit signal transduction mediated by protein kinases (Abstract).
The teachings are Teng, et al. are set forth above.
Regarding claim 21: Benjahad, et al. teaches a WST-1 cell survival/proliferation assay in primary human adult cardiomyocytes, wherein cardiomyocytes were plated in a 96-well plate; after adherence, cells were treated with a drug solution for 48h then incubated with WST-1 reagent before the formation of formazan dye was quantified by its absorbance at 450 nm using a spectrophotometer (pg. 59; lines 1-25).
The WST-1 assay taught by Benjahad, et al. reads on the method for determining the ability of a compound to reduce cell viability limitation recited in claim 21, the limitations recited in steps b), c), and d) of claim 22, the wherein the indicator compound is an indicator dye limitation recited in claim 23, and the wherein the signal of the indicator compound is an absorbance signal limitation recited in claim 24.
Benjahad, et al. does not teach the recombinant cardiomyocytes stably expressing or overexpressing hERG limitation recited in these claims.
However, Teng, et al. teaches embryonic stem cell-derived cardiomyocytes overexpressing N629D (pg. 270; col. 1, par. 1), a hERG1 mutation (pg. 268; col. 2, par. 1). As set forth above, under broadest reasonable interpretation, the term stably expressing hERG recited in claim 21 is interpreted as any level of expression of hERG, and does not necessarily exclude overexpression of hERG. Therefore, the N629D-overexpressing cardiomyocytes of Teng, et al. read on the recombinant cardiomyocytes stably expressing hERG limitation recited in claim 21, as well as the recombinant cardiomyocytes overexpressing hERG limitation recited in step a) of claim 22.
It would have been prima facie obvious to a person having ordinary skill in the art to have modified the method of Benjahad, et al. by substituting the primary cardiomyocytes with the N629D-overexpressing cardiomyocytes of Teng, et al. This conclusion of obviousness is based on the ‘substitution rationale’. The use of the N629D-overexpressing cardiomyocytes in place of the primary cardiomyocytes is a predictable use of prior art elements according to their established functions as cardiac cells, leading to the predictable result of determining cell survival/proliferation of cardiomyocytes in response to a drug. This rationale aligns with the principle of a simple substitution of one known element for another to obtain predictable results; see MPEP 2143(I)(B). Therefore, claims 21-24 are rendered obvious over Houghton, et al., in view of Teng, et al.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GINA PRONZATI whose telephone number is (571)270-5725. The examiner can normally be reached Monday - Friday 9:00a - 5:00p ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, CHRISTOPHER BABIC can be reached at (571)272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/GINA PRONZATI/Examiner, Art Unit 1633
/ALLISON M FOX/Primary Examiner, Art Unit 1633