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 .
Election/Restrictions
Applicant’s election without traverse of Group II, claims 52 and 85-103 in the reply filed on 10/21/2025 is acknowledged.
Claims 1, 2, 10, 13, 14, 26, 28-30, 32, 33, 35-38, 61, 70, 76 and 80 have been cancelled. Claim 52 has been amended. Claims 85-103 have been added. Upon entry of
the amendments, claims 52 and 85-103 are pending in the application.. Election was made without traverse in the reply filed on 10/21/2025.
Claims 52, and 85-103 are currently under examination.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 62964477, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. For example, application No. 62964477 does not provide support for the inducible promoter recited in claim 1. However, support for these limitations are found in the prior-filed application 16953002. Therefore, the priority date for the instant claims is 11/19/2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted was filed before the mailing date of the non-final first action on the merits. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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 87 and 89 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 87 and 89 recite inherent characteristics that flow from performing the steps of the method. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 52, 86-87, 90, and 92-97 are rejected under 35 U.S.C. 103 as being unpatentable over Wakatsuki et al (US 2014/0094388 A1) .
Regarding claims 52, Wakatsuki et al teach an engineered cardiac tissue construct and methods of using these constructs. ( See abstract). The cardiac construct of Wakatsuki et al comprises of two cell populations including cardiomyocytes (i.e. second population/parenchymal), and fibroblasts (i.e. non-parenchymal cells/ first population/stromal cells), as well as extracellular matrix component ([0023]). Wakatsuki et al teach that the cells for making the cardiac construct may be derived from any suitable animal, including but not limited to, human, mouse, rat, pig, cow, dog, guinea pig, etc. (i.e., mammalian cell populations) ([0025]). Wakatsuki et al state that “the fibroblasts can overwhelm the cardiomyocytes by replication such that the resulting tissue does not have the functional properties of cardiac tissue. Thus, the growth of the fibroblasts may need to be limited” ([0032]). According to Wakatsuki et al, the growth ability of the fibroblast cells can be limited by several methods or any means known to those of skill in the art ([0023], [0027]). Among the methods that Wakatsuki et al suggest to limit the growth of the fibroblast cells is by genetically engineering the fibroblast cells to express a suicide gene that can be activated by a small molecule to induce cell killing or inhinting their growth, this reads on step (a) ([0029]). For example, Wakatsuki et al state that “ the fibroblasts may be transfected with the thymidine kinase gene from Herpes Simplex Virus such that the fibroblast cells become sensitive to an antiviral such as ganciclovir” ([0029]). It should be noted that the thymidine kinase gene is an apoptosis-inducing polypeptide that reads on instant claim. Wakatsuki et al also state that “The cardiac tissues may be formed on a scaffold support disposed within a well”, this reads on step (b) ([0003]).
Taken together, Wakatsuki et al teach a method of producing engineered heart construct comprising of non-parenchymal cell population (i.e. fibroblast) and a second population (i.e. cardiomyocytes). Wakatsuki et al further suggest that the non-parenchymal cells can be eliminated from the tissue construct by genetically engineering the non-parenchymal cells to express a suicide gene. Wakatsuki et al do not specifically exemplify the method of elimination (i.e. step (c)). However, claim 1 would have been obvious to one of ordinary skill in the art at the time the invention was filed, as there was some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. Because Wakatsuki et al teach a method for making tissue construct comprising of two cell populations, and clearly suggest that the non-parenchymal cell population in the tissue construct can be eliminated by genetically engineering the cells to express a suicidal gene such as thymidine kinase, wherein the cells are eliminated by contacting the tissue construct with an antiviral (e.g. ganciclovir). There is a reasonable expectation of success, when making a tissue construct, to genetically engineer the non-parenchymal cells to express a suicide gene because doing so which would provide the system with a temporal control, such as controlling the growth of the non-parenchymal cell population in the tissue construct.
Regarding claim 86, Wakatsuki et al further teach that the tissue construct may further comprises co-culturing the cells with a third cell population comprising endothelial cells. (See claim 12).
Regarding claim 87, Wakatsuki et al do not explicitly state that the endothelial cells self-assemble into vasculature. However, such result is an inherent property as it recites functional outcome. This functional outcome is considered inherent, because the active step of the claims (i.e. coculturing parenchymal cell (cardiomyocytes) with non-parenchymal cell populations including fibroblast and endothelial cells) is taught by Wakatsuki et al, and there is nothing in applicants' disclosure that shows that these functional outcomes come from something other than the claimed method step. The method of Wakatsuki et al involves the same active step of instant application. Therefore, the method of coculturing cardiomyocytes with fibroblast and endothelial cells will inherently result in this functional outcome i.e. the self-assembly of the endothelial cells into vasculature.Regarding claims 90, 92-97, Wakatsuki et al’s tissue construct comprises of two or more cell populations including cardiomyocytes, fibroblast, and may further contain endothelial cells, wherein the cardiomyocytes represent the “parenchymal cell population” and the fibroblast and endothelial cells represent the stromal/non-parenchymal cells. ( See claims 1 and 12).
Claim(s) 85, and 98-103 are rejected under 35 U.S.C. 103 as being unpatentable over Wakatsuki et al as applied to claims 52, 86, 90, and 92-96 above, and further in view of Slawin et al (US 2016/0151465 A1).
Regarding claims 85, 98-103, the teaching of Wakatsuki et al are set forth above. Wakatsuki et al teach a tissue construct comprising a non-parenchymal cell population that is engineered to express a suicide gene in order to control their growth within the construct. However, Wakatsuki et al do not teach the use of a suicide gene, wherein the gene is an inducible caspase 9, nor do they teach contacting the cells with a small molecule to activate apoptosis-inducing polypeptide in vivo.
Slawin et al teach a method for partial apoptosis of cells that express an inducible caspase polypeptide or a modified version of it (Abstract). The method involves engineering therapeutic cells, such as T cells, to express a caspase or a modified version whose activation can be externally triggered, allowing for the tuned elimination of only caspase-expressing cells. Slawin et al utilize an inducible caspase-9 system, in which caspase 9 may have an inducible dimerization domain. (See abstract, [0008],[0010], and [0012]). Slawin et al also demonstrate in vivo contacting the cells with the small molecule to induce the killing of the cells expressing the inducible caspase 9 ( [0353]).
Therefore, claims 85, and 98-103 would have been obvious to one of ordinary skill in the art at the time the invention was filed, as there was some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. Because Wakatsuki et al teach a method for making tissue construct comprising of two cell populations, and clearly suggest that the non-parenchymal cell population in the tissue construct can be eliminated by genetically engineering the cells to express a suicidal gene such as thymidine kinase, wherein the cells are eliminated by contacting the tissue construct with an antiviral (e.g. ganciclovir). Slawin et al teach a method for engineering therapeutic cells expressing inducible caspase-9, allowing for the tuned elimination of only a subset of caspase-expressing cells. Slawin et al additionally teach that thymidine kinase, as taught by Wakatsuki, can result in adverse immune responses ([0320]). Therefore, an ordinary skill in the art would be motivated would to use a suicide gene that does not have adverse immunological effects. There would be a reasonable expectation of success in using the inducible caspase 9 of Slawin, instead of the thymidine kinase as taught by Wakatsuki, because Slawin et al demonstrate that caspase-9 can be used in cells to induce apoptosis. One would expect similar results since both references use suicide genes to induce cell apoptosis.
Claims 86-97 are rejected under 35 U.S.C. 103 as being unpatentable over Wakatsuki et al as applied to claims 52, 86, 90, and 92-96 above, and further in view of Chen et al (WO 2017/062757 A1).
Regarding claims 86-97, the teaching of Wakatsuki et al are set forth above. Wakatsuki et al teach a tissue construct comprising an engineered non-parenchymal cells that express a suicide gene, allowing for the tuned elimination of only a subset of caspase-expressing cells . However, Wakatsuki et al do not teach a tissue construct wherein the parenchymal cells are hepatocyte or hepatocytes precursor.
Chen et al teach a tissue construct comprising of: a first cell population of primary human hepatocytes (i.e. parenchymal cell) ; a second cell population of human fibroblasts (i.e. first non-parenchymal cell) ; a third cell population of primary human endothelial cells (i.e. second non-parenchymal cell) ; and a biocompatible hydrogel scaffold ( See claim 1). Chen et al also teach that the tissue construct is suitable for implantation into a host (claim 1). Chen et al further teach that the third cell population (i.e. endothelial cells) is seeded into a pre-templated
vessels in the substrate to promote vascularization of the engineered tissue construct. (See claims 18-19, and section “ Vascular Cell and Endothelial Cell Cords” on page 25-26). Chen et al do not teach a tissue construct wherein one of the non-parenchymal cell population express a suicide gene. However, claims 86-97 is combining prior art elements according to known methods to yield predictable results, namely the predictable result being a tissue construct comprising of parenchymal and non-parenchymal cell populations, and wherein the non-parenchymal cell population is engineered to express suicide gene. Because Wakatsuki et al teach a method for making tissue construct comprising of parenchymal cells and non-parenchymal cell populations, wherein the parenchymal cell population comprising of cardiomyocytes, but fails to teach a construct comprising of hepatocytes. Chen et al teach a tissue construct that is suitable for transplantation into a host, wherein the construct comprises of primary human hepatocytes; human fibroblasts ; and a third cell population of primary human endothelial cells. Therefore, an ordinary skill in the art who had reviewed Wakatsuki et al could have come across Chen et al and immediately noticed the strong possibility that making a tissue construct comprising of hepatocytes as the parenchymal cell type, instead of cardiomyocytes of Wakatsuki et al, would have the predictable result of generating a tissue construct suitable for transplantation into a host.
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 52, and 83-103 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1,26,28,30,32-33,36-38,86-95 of copending Application No. 16953002. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of copending Application No. 16953002 are directed to a tissue construct comprising of one parenchymal cell population, and one or more non-parenchymal cell populations, wherein the growth of one of the non-parenchymal cell population is controlled by engineering the cells to express a suicide gene such as inducible caspase 9.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FATIMAH KHALAF MATALKAH whose telephone number is (703)756-5652. The examiner can normally be reached Monday-Friday,7:30 am-4:30 pm EST.
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/FATIMAH KHALAF MATALKAH/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638