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 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 2 and 4 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.
Claims 2 and 4 recite a cell density of 2.0x105 to 5.0x105 cells/cm2, “and preferably 2.0x105 to 4.0x105 cells/cm2,” a narrow range lying within the broader one. MPEP 2173.05(c) instructs, “Use of a narrow numerical range that falls within a broader range in the same claim may render the claim indefinite when the boundaries of the claim are not discernible. If stated in a single claim, examples and preferences lead to confusion over the intended scope of the claim. In those instances where it is not clear whether the claimed narrower range is a limitation, a rejection under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph should be made.” Such is the case here because it is unclear whether claims 2 and 4 permit 5x105 cells/cm2 or is limited to the narrower preferred range.
Claim Rejections - 35 USC § 102 and 103
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.
(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.
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.
Claims 1, 2, 10, 11, 23, and 24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lancaster et al. (US 2016/0250384). This rejection addresses the interpretation of claim 1 in which the phrase “seeded at a cell density of 0.1x105 to 5.0x105 cells/cm2 in a culture solution” refers to the “culturing” step.
Lancaster teaches seeding 1.3x105 to 2.7x106 cardiomyocytes per cm2 in a culture medium. (Paragraph 50.) Regarding claim 10, Lancaster teaches that the cardiomyocytes are derived from iPSCs. (Paragraph 49.) Regarding claim 24, Lancaster teaches that the resulting culture is for therapeutic use. (Paragraph 50.) Lancaster carries out the same active step as that claimed, so the method inherently results in proliferation of cardiomyocytes (claim 1, lines 4-5; claim 11, lines 1 and 4-5). See MPEP 2112.02.
Claims 1, 2, 11, 23, and 24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nakayama et al. (US 2019/0040359). This rejection addresses the interpretation of claim 1 in which the phrase “seeded at a cell density of 0.1x105 to 5.0x105 cells/cm2 in a culture solution” refers to the “culturing” step.
Nakayama teaches seeding cardiomyocytes at a cell density of 2.5x105/cm2. (Paragraphs 1384-1385; Table 4.) Regarding claims 13 and 24, Nakayama’s starting material is a suspension of cardiomyocytes and is therefore a “transplantation material.” (See as-filed specification at page 40, lines 9-15.) Nakayama carries out the same active step as that claimed, so the method inherently results in proliferation of cardiomyocytes (claim 1, lines 4-5; claim 11, lines 1 and 4-5). See MPEP 2112.02.
Claims 1, 2, 9-11, 23, and 24 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Sueta et al. (WO 2019/131806, published 7/4/19, effectively filed 12/26/17; on 12/7/22 IDS) as evidenced by Hikita et al. (US 20130196369). Sueta was published in Japanese, but US 2021/0372993 is the publication of its US national-stage application and therefore serves as an English translation. This rejection addresses the interpretation of claim 1 in which the phrase “seeded at a cell density of 0.1x105 to 5.0x105 cells/cm2 in a culture solution” refers to the “culturing” step.
Sueta teaches seeding 4x104 to 8x104 cardiomyocytes differentiated from human iPS cells per well of a 96-well plate and culturing for 7 days to produce beating sheets. (Paragraph 321.) Hikita is cited solely as evidence that the surface area of each well in a 96-well plate is inherently 0.32cm2 (paragraph 33), meaning Sueta seeded 1.25 x105 to 2.0x105 cardiomyocytes per cm2. Regarding claims 13 and 24, Sueta’s starting material is a suspension of cardiomyocytes and is therefore a “transplantation material.” (See as-filed specification at page 40, lines 9-15.) Sueta carries out the same active step as that claimed, so the method inherently results in proliferation of cardiomyocytes (claim 1, lines 4-5; claim 11, lines 1 and 4-5). See MPEP 2112.02.
Claims 1, 2, 8-11, 23, and 24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Uosaki et al. (2013, Circulation: Cardiovascular Genetics 6: 624-633; on 12/7/22 IDS) as evidenced by Hikita et al. (US 20130196369). This rejection addresses the interpretation of claim 1 in which the phrase “seeded at a cell density of 0.1x105 to 5.0x105 cells/cm2 in a culture solution” refers to the cardiomyocytes themselves, i.e., it is a product-by-process limitation.
Uosaki teaches seeding 500 embryonic-stem-cell derived cardiomyocytes per well in a 96-well plate. (Page 625, column 1.) Hikita is cited solely as evidence that the surface area of each well in a 96-well plate is inherently 0.32cm2 (paragraph 33), meaning Uosaki seeded 1.6 x103 cardiomyocytes per cm2. Uosaki teaches that ES-derived cardiomyocytes (mESCM) cultured in this way proliferate in the culture and then begin to beat. (Page 625, column 2.) Uosaki further teaches that his mESCM express the cardiac marker troponin-T, are largely binuclear, and generate cardiomyocyte-like action potentials. (Page 626; page 628, column 2, through page 629, column 1.) Regarding claim 9, Uosaki discloses that cardiomyocytes derived from human iPSCs spontaneously beat and show clear sarcomere formation and action potentials. (Page 630.) Regarding claim 24, Uosaki’s starting material is a suspension of cardiomyocytes and is therefore a “transplantation material.” (See as-filed specification at page 40, lines 9-15.)
The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process. Once a product appearing to be substantially identical is found and a prior-art rejection is made, the burden shifts to the applicant to show a nonobvious difference between the claimed product (proliferating cardiomyocytes seeded at a particular cell density) and the prior art’s (proliferating cardiomyocytes seeded at a different cell density). Uosaki’s cultured cardiomyocytes, which were derived from cultured pluripotent stem cells, show the properties and abilities of cardiomyocytes just as applicant’s do. The burden therefore shifts to the applicant to show that the seeding density and, for claim 8, the use of serial subculturing, affects the properties of cardiomyocytes. This rejection would also be overcome by amending claim 1 to require an active step of seeding cardiomyocytes a cell density of 0.1x105 to 5.0x105 cells/cm2 in a culture solution.
Claims 1-11, 23, and 24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Shim et al. (WO 2015/119575; on 4/12/23 IDS). This rejection addresses the interpretation of claim 1 in which the phrase “seeded at a cell density of 0.1x105 to 5.0x105 cells/cm2 in a culture solution” refers to the cardiomyocytes themselves, i.e., it is a product-by-process limitation.
Shim teaches seeding embryoid bodies (EBs) from human iPSC/hESC cells in a vessel and culturing them with, among other things, (a Wnt agonist; page 18, line 4) or AG1478 (an EGF receptor inhibitor; page 25, line 5) in DMEM-F12 medium supplemented with fetal bovine serum. (Page 20, line 12, through page 21, line 10.) Shim teaches that EBs treated in this way differentiate into begin to beat. (Page 21, lines 6-10.) Shim teaches that the beating occurs between days 10-14 and that AG1478 or CHIR99021 was added from days 4-14 (page 21, lines 4-8), meaning that from days 10-14, Shim’s culture comprises cardiomyocytes and either AG1478 or CHIR99021. Regarding claim 24, Shim teaches dissecting the beating areas from the culture, which generates patches (layers) of cardiomyocytes and is therefore a “transplantation material.” (See as-filed specification at page 40, lines 9-15.)
The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process. Once a product appearing to be substantially identical is found and a prior-art rejection is made, the burden shifts to the applicant to show a nonobvious difference between the claimed product (proliferating cardiomyocytes seeded at a particular cell density) and the prior art’s (proliferating cardiomyocytes seeded at a different cell density). Shim’s cultured cardiomyocytes, which were derived from cultured pluripotent stem cells) show the properties and abilities of cardiomyocytes just as applicant’s do. The burden therefore shifts to the applicant to show that the seeding density affects the properties of cardiomyocytes. This rejection would also be overcome by amending claim 1 to require an active step of seeding cardiomyocytes a cell density of 0.1x105 to 5.0x105 cells/cm2 in a culture solution.
Claim 5 is rejected under 35 U.S.C. 103 as obvious over each of Lancaster, Nakayama, Uosaki, and Shim in view of Sueta (WO 2019/131806, published 7/4/19, effectively filed 12/26/17; on 12/7/22 IDS).
The teachings of Lancaster, Nakayama, Uosaki, and Shim are applied as set forth above.
Lancaster, Nakayama, Uosaki, and Shim do not teach culturing such that the distance between a liquid surface of the culture solution and the culture-vessel bottom surface (“liquid-surface distance”) is 3-30mm.
Sueta teaches that in culturing cardiomyocytes, the liquid-surface distance is 5.0 mm or less. (Paragraph 105 of US 2021/0372993.) Sueta further teaches that this distance can be varied by changing the amount of the culture medium. (Paragraph 109.)
It would have been obvious to vary the liquid-surface distance in each of Lancaster, Nakayama, Uosaki, and Shim to between 3-30mm because Sueta teaches a distance within the claimed range and teaches that optimizing the distance could be achieved by varying the amount of culture medium employed. Sueta’s liquid-surface distance of “5mm or less” overlaps with the claimed range of “3-30mm,” so Sueta establishes prima facie obviousness of the claimed range. In the alternative, the liquid-surface distance is a result-effective variable that can be changed according to routine optimization. See MPEP 2144.05(I) and (II).
Claim 5 is rejected under 35 U.S.C. 103 as obvious over Sueta (WO 2019/131806, published 7/4/19, effectively filed 12/26/17; on 12/7/22 IDS).
The teachings of Sueta are applied as set forth above. In addition, Sueta teaches that in culturing cardiomyocytes, the liquid-surface distance is 5.0 mm or less. (Paragraph 105 of US 2021/0372993.) Sueta further teaches that this distance can be varied by changing the amount of the culture medium. (Paragraph 109.)
It would have been obvious to vary the liquid-surface distance in each of Sueta to between 3-30mm because Sueta teaches a distance within the claimed range and teaches that optimizing the distance could be achieved by varying the amount of culture medium employed. Sueta’s liquid-surface distance of “5mm or less” overlaps with the claimed range of “3-30mm,” so Sueta establishes prima facie obviousness of the claimed range. In the alternative, the liquid-surface distance is a result-effective variable that can be changed according to routine optimization. See MPEP 2144.05(I) and (II).
Claims 12 and 13 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Olivetti et al. (1996, Journal of Molecular and Cellular Cardiology 28: 1463-1477; reference U).
Claim 12 refers to human multinucleated cardiomyocytes with three or more nuclei, derived in some way from pluripotent stem cells. The limitations “human” and “derived from pluripotent stem cells” define the cells by their source material rather than by any structural requirement. See MPEP 2113: “The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” The phrase “derived from pluripotent stem cells” does not particularly limit the nature of the derivation; it does not require, for example, that the cardiomyocytes be differentiated in vitro from cultured pluripotent stem cells. Cardiomyocytes are inherently “derived from pluripotent stem cells,” namely the pluripotent cells found within the blastocyst that give rise to the entire human body during embryonic development.
Olivetti teaches enzymatically dissociated human cardiomyocytes (i.e., a cardiomyocyte population) and indicates that 0.4% of them are trinucleated. (Abstract; page 1469, column 1.) Regarding claim 13, Olivetti’s solution is a suspension of cardiomyocytes and is therefore a “transplantation material.” (See as-filed specification at page 40, lines 9-15.) There is nothing in the record to suggest that human cardiomyocytes isolated directly from heart muscle are structurally different from human cardiomyocytes derived from pluripotent stem cells, so the burden shifts to applicant to show a patentable difference.
Claims 14 and 15 are rejected under 35 U.S.C. 102(a) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Soonpaa et al. (1997, Journal of Clinical Investigation 99: 2644-2654; reference V).
Claims 14 and 15 refer to human multinucleated cardiomyocytes with five or more nuclei. The limitation “human” defines the cells by their source material rather than by any structural requirement. See MPEP 2113: “The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.”
Soonpaa teaches cyclin D1-overexpressing mouse multinucleated cardiomyocytes with five nuclei. (Page 2649, column 2; Figure 6C and 6G.) Soonpaa teaches that translocations involving the cyclin D1 locus are associated with tumorigenesis in humans. (Page 2645, column 1.) There is nothing in the record to suggest that mouse cells overexpressing cyclin D1 are structurally different from human tumor cells that overexpress cyclin D1, so the burden shifts to applicant to show a patentable difference.
Claim 25 is rejected under 35 U.S.C. 103 as obvious over Shim et al. (WO 2015/119575; on 4/12/23 IDS).
Shim teaches culturing embryoid bodies (EBs) in a medium comprising either CHIR99021 (a Wnt agonist) or AG1478 (an EGF receptor inhibitor), thereby yielding cardiomyocytes after 4-14 days. (Page 20, line 12, through page 21, line 10.) Shim does not teach replacing the medium once cardiomyocytes differentiate from the EBs at days 10-14, so the culture on those days contains all components that were originally added plus the cardiomyocytes that have differentiated during that time.
Shim does not teach a composition containing both a Wnt agonist and an EGF receptor inhibitor. Shim teaches, however, that both CHIR99021 (a Wnt agonist) or AG1478 (an EGF receptor inhibitor) stimulate cardiomyocyte differentiation from EBs. Shim therefore demonstrates that these compounds are functional equivalents for each other. Combining equivalents known for the same purpose is prima facie obvious. See MPEP 2144.06(I) (quoting In re Kerkhoven, 626 F.2d 846, 850, 205 U.S.P.Q. 1069, 1072 (C.C.P.A. 1980)). There is no limiting definition in the examined specification for the word “kit,” so the term does not require any particular structural properties or configurations, so Shim renders the claimed kit obvious.
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, 2, 5, 9-11, and 23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 11,726,083. Although the claims at issue are not identical, they are not patentably distinct from each other.
The ’083 patent claims a method comprising testing a drug response of cardiomyocytes wherein the cell density of the cardiomyocytes is, for example, greater than or equal to 2.5x105 cells/cm2 and the distance from the liquid surface of the culture medium to the bottom surface of the culture vessel is 1.5mm or less. (Claim 1; element (i).) The ’083 patent claims the same active step as that claimed, so the method inherently results in proliferation of cardiomyocytes (claim 1, lines 4-5; claim 11, lines 1 and 4-5). See MPEP 2112.02.
Regarding claims 9 and 10, the ’083 patent is silent as to the source of the cardiomyocytes, but the limitations of “human” and “obtained by inducing differentiation of pluripotent stem cells into cardiomyocytes” are product-by-process limitations. See MPEP 2113: “The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” The phrase “obtained by inducing differentiation of pluripotent stem cells into cardiomyocytes” does not particularly limit the nature of the derivation; it does not require, for example, an active step in which cardiomyocytes be differentiated in vitro from cultured pluripotent stem cells. Cardiomyocytes are inherently “derived from pluripotent stem cells,” namely the pluripotent cells found within the blastocyst that give rise to the entire human body during embryonic development.
Claim Objections
Claims 16-22 are 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 the base claim and any intervening claims.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LORA E BARNHART DRISCOLL, whose telephone number is (571)272-1928. The examiner can normally be reached M-F 7:00-4:00 p.m. ET.
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/Lora E Barnhart Driscoll/Primary Examiner, Art Unit 3991