DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
This application was filed 8/17/2022. Twenty-eight original claims were presented. It appears papers (preliminary amendment to claims, spec and response to a restriction requirement) intended for a different application were inadvertently filed in this application on 8/17/2022. The “amended” claims filed on 8/17/2022 include 49 claims that are not related to the originally filed claims. The 8/17/2022 “amendment” is not being considered for this application.
On 6/14/2023 a [proper] preliminary amendment was filed in this application. This preliminary amendment is vis-à-vis the originally filed claims. Claims 1-3, 5-11, 15-23, and 25 are presented. All of these claims have been considered on the merits.
Priority
Acknowledgement is made of Applicants’ claim for benefit as a continuation under 35 USC 120 of prior filed US application No. 16/243592 (filed 1/9/2019, now US Patent 11452797), which claims benefit under 35 USC 121 as a divisional of prior-filed US Application No. 14/777360 (filed 9/15/2015, now US Patent 10213525), which is a national stage entry of PCT/US2014/026363 (filed 3/13/2014), which claims benefit of prior-filed US Provisional Application No 61/789927 (filed 3/15/2013).
Claim Objections
Claims 1, 7, and 25 are objected to for minor informalities:
In claim 1, at lines 13-14 “re endothelialized” should be hyphenated or a single word.
In claim 7, the full term “induced pluripotent stem cells” should precede the abbreviation iPS (the full term should precede the first use of the abbreviation).
The formatting of claim 25 makes it difficult to understand. It appears there are three separate embodiments/alternatives claimed. It is recommended to enumerate the options with a), b) and c), or the like, e.g.25. A method to enhance insulin control in a mammal that lacks or has reduced insulin control, comprising:
providing a re-endothelailized extracellular matrix …., and
introducing to a mammal that lacks or has reduced insulin control the re-endothelialized matrix ….; or
providing a re-endothelialized extracellular matrix…,
introducing to a mammal that lacks or has reduced insulin control the re-endothelialized matrix, and
introducing to the mammal having the re-endothelialized matrix a population of cells including….; or
providing a mammal that lacks or has reduced insulin control and has an implanted re-endothelialized matrix of a mammalian liver,…, and
introducing into the mammal a population of cells including…
In claim 25 at lines 20-21 “re endothelialized” should be hyphenated or a single word.
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 1-3, 5-11, 15-23 and 25 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 claim 1: There are two issues with claim 1 that render it indefinite:
First: A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
In the present instance, claim 1 at lines 3-4, recites the broad recitation “selecting a perfusion decellularized extracellular matrix of a mammalian liver, a liver lobe, or a portion thereof…” (permitting for the perfusion decellularized ECM (dECM) to be any of a liver, a liver lobe or a portion thereof), yet, at lines 9-11, the claim also recites the narrower limitation “the selected perfusion dECM is a portion… of a liver lobe (limiting the perfusion dECM to be a portion of a liver lobe). The claim is considered indefinite because it is unclear if the perfusion dECM can be the full mammalian liver or a liver lobe, or if it must be only a portion of a liver lobe measuring >8 cm3 in size.
Second: It is unclear what “insulin like cells” encompasses. “Insulin like cells” is not a term of the art, and no definition is provided in the specification. It cannot be determined what cells could be considered “insulin like” and thus the metes and bounds of the claim are unclear.
Claims 2, 3, 5-11, 15-23 depend from claim 1, inherit the deficiency and are rejected on the same basis.
Regarding claim 8: It is unclear how a decellularized ECM contains an intact vascular network? An intact vascular network would include endothelial cells. A decellularized ECM would contain no cells. The graft, following re-endothelialization, may contain an intact vascular network.
Regarding claim 16: There is insufficient antecedent basis for the limitation “the insulin producing cells” in line 2.
Regarding claim 25: There are two issues with claim 2 that render it indefinite.
First: At line 8, it is unclear what “the population” refers to. It appears to be a typographical error for “the population of mammalian cells”, but even then it is unclear if it is referring to the population of mammalian cells including islet cells, beta cells, islet like cells or stem cells or progenitor cells capable of differentiation into islet cells or beta cells, or to the population of mammalian endothelial cells.
Second: it is unclear what an “islet like cell” encompasses. “Islet like cells” is not a term of the art, and there is no definition provided in the specification. It cannot be determined what cells could be considered “islet like” and thus the metes and bounds of the claim are unclear.
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 2 and 3 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 2 and 3 appear to attempt to further limit the perfusion dECM to a liver or a liver lobe, respectively. But for the reasons set forth above under 35 USC 112(b), claim 1 already limits the perfusion dECM to a portion of a liver lobe. Thus claims 2 and 3 do not appear to properly further limit parent claim 1.
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 § 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 1-3, 5-11, 15-22, and 25 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification fails to provide enablement for the full scope of the claims.
Generally, claim 1 is drawn to a method to prepare a graft comprising a recellularized ECM of a mammalian liver. The method generally comprises (i) selecting a perfusion dECM, a first population of cells, and a second population of cells, wherein the first population of cells is endothelial cells, or stem or progenitor cells capable of differentiating into endothelial cells, and the second population is islet cells, beta cells, insulin like cells, or stem or progenitor cells capable of differentiating into islet or beta cells; then (ii) contacting the perfusion dECM with the first and second populations of cells under conditions that will result in re-endothelialization of the dECM with endothelial cells, and recellularization of the dECM with islet cells, beta cells, or insulin like cells.
The scope of claim 1 permits for either the first and/or second populations of cells to be stem or progenitor cells, and for the ‘contacting’ to be under conditions effective to cause differentiation of the stem or progenitor cells to endothelial cells and/or islet cells or beta cells, respectively.
The scope of claim 1 permits for the first and/or second populations of cells to be provided to the perfusion dECM (i.e. the ‘contacting’) to be ex vivo or in vivo. Claims 19-22 specify embodiments where at least one cell population is ‘contacted’ with the dECM in vivo.
Generally, claim 25 is drawn to a method to enhance insulin control in a mammal that lacks or has reduced insulin control, comprising providing to the individual a recellularized ECM of a mammalian liver. Claim 25 provides for three different embodiments, for ease of reference, they will be referred to as a)-c) (as set forth in the Claim Objection section).
In embodiment a), the method generally comprises: (i) providing a re-endothelialized dECM of mammalian liver, said re-endothelialized dECM further including a second cell population, wherein the second cell population includes beta cells, islet like cells, or stem or progenitor cells capable of differentiating into islet cells or beta cells. Then (ii) introducing the re-endothelialized dECM containing the islet cells, beta cells, islet like cells, or stem or progenitor cells capable of differentiating into islet cells or beta cells into the mammal.
In embodiment b), the method generally comprises: (i) providing a re-endothelialized dECM of mammalian liver; (ii) introducing the re-endothelialized dECM into the mammal; and then (iii) introducing to the mammal a second cell population, wherein the second cell population includes beta cells, islet like cells, or stem or progenitor cells capable of differentiating into islet cells or beta cells.
In embodiment c), the method generally involves: (i) providing a mammal that has implanted within them, a re-endothelialized dECM of mammalian liver; then (ii) introducing to the mammal a second cell population, wherein the second cell population includes beta cells, islet like cells, or stem or progenitor cells capable of differentiating into islet cells or beta cells.
For all three embodiments, emphasis is placed on re-endothelialized dECM because it means that mature endothelial cells are present on the dECM that is provided in step (i). All three embodiments permit for (and embodiments b) and c) require)) ‘delivery’ of the second cell population to the endothelialized dECM after placement in vivo.
The specification is enabling for all claim embodiments where the first and second cell populations are mature endothelial cells or islet or beta cells, respectively. These mature cells can be provided to the dECM ex vivo, or supplied to the dECM following implantation of the dECM into a subject.
The issue at hand is for the claim embodiments wherein the first and/or second cell populations comprise stem or progenitor cells capable of differentiating into endothelial cells, or islet cells or beta cells, respectively. The specification is enabling for preparing the graft (claim 1) and enhancing insulin control in a mammal in need thereof (claim 25) only when the stem or progenitor cells are provided to the dECM in vitro, and then the stem or progenitor cells are cultured under conditions effective to differentiate the stem or progenitor cells to endothelial cells or islet or beta cells, respectively. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make the graft by delivering stem or progenitor cells capable of differentiating into endothelial cells, or islet cells or beta cells to a mammal having the [re-endothelialized] dECM already implanted (claim 1) or to enhance insulin control in a subject in need thereof by delivering stem or progenitor cells capable of differentiating into islet or beta cells to a mammal having the re-endothelialized dECM already implanted (claim 25).
Analysis of whether a particular claim is supported by the disclosure in an application requires a determination of whether that disclosure, when filed, contained sufficient information regarding the subject matter of the claims as to enable one skilled in the pertinent art to make and use the claimed invention without undue or unreasonable experimentation. See Mineral Separation v. Hyde, 242 U.S. 261, 270 (1916). The key word is 'undue,' not experimentation.' " (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required are summarized In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988). The factors to be considered in determining whether undue experimentation is required include: (1) the quantity of experimentation necessary, (2) the amount or direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. While all these factors are considered, a sufficient number are discussed below so as to create a prima facie case.
In the instant case, for the embodiments that require provision of stem or progenitor cells, it is necessary that the stem or progenitor cells be provided under in vitro conditions effective to direct their differentiation to endothelial cells or islet or beta cells in order to produce a re-endothelialized graft that is recellularized with islet cells or beta cells. At the time the invention was made, methods for directing differentiation of stem cells (including embryonic stem cells and induced pluripotent stem cells) to endothelial cells and/or islet cells or beta cells in vitro were taught in the art (See Taylor et al WO 12/031162 (disclosure of differentiating pluripotent stem cells to endothelial cells); D’Amour et al, Nat Biotech, 2006 (disclosure of differentiating pluripotent stem cells to insulin-producing cells). The methods required controlled in vitro cell culture conditions.
Neither the specification, nor the prior art, teach methods wherein stem or progenitor cells (such as ESCs or iPSCs) can be directly injected to a subject, home to an implanted dECM, and then reliably differentiate to endothelial cells or islet or beta cells. Particularly when the dECM is from liver tissue, not pancreatic tissue.
In the absence of guidance or teachings in the art, and lack of any working examples, the embodiments of the claims wherein stem or progenitor cells capable of differentiating into endothelial cells, or islet cells or beta cells are delivered to a mammal having the [re-endothelialized] dECM already implanted are not found to comply with 35 USC 112(a). Claims 1-3, 5-11, 15-22, and 25 are rejected. It is noted that claim 23 is limited to embodiments wherein the first and second populations of cells are provided prior to implantation of the dECM into a mammal, and thus claim 23 is enabled.
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 1-3, 5-11, 15-23 and 25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 10213525.
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims anticipate and/or render obvious the instant claims, as follows:
Regarding claims 1-3: Patented claim 1 teaches all limitations of instant claims 1-3, except patented claim defines the second cell population as comprising insulin producing cells or stem cells or precursors thereof, whereas instant claim 1 defines the second cell population as islets or beta cells, or stem or precursors thereof. However, patented claim 20 defines the insulin producing cells as islet cells or beta cells, thereby teaching the remaining claim limitation.
Regarding claims 5 and 6: Following the discussion of claim 1 above, patented claim 3 teaches the limitations of instant claims 5 and 6.
Regarding claims 7 and 15: Following the discussion of claim 1 above, patented claim 4 teaches the limitations of instant claims 7 and 15.
Regarding claim 8: Following the discussion of claim 1 above, patented claim 5 teaches the limitations of instant claim 5.
Regarding claim 9: Following the discussion of claim 1 above, patented claim 6 teaches the limitations of instant claim 9.
Regarding claim 10: Following the discussion of claim 1 above, patented claim 7 teaches the limitations of instant claim 10.
Regarding claim 11: Following the discussion of claim 1 above, patented claim 8 teaches the limitations of instant claim 11.
Regarding claim 16: Following the discussion of claim 1 above, patented claim 10 teaches the limitations of instant claim 16.
Regarding claim 17: Following the discussion of claim 1 above, patented claim 11 teaches the limitations of instant claim 17.
Regarding claims 18-23: Following the discussion of claim 1 above, patented claims 12-17 teaches the limitations of instant claims 18-23, respectively.
Regarding claim 25: Following the discussion of claim 1 above, patented claims 12-17 render obvious the different embodiments of claim 25.
Claims 1-3, 5-11, 15-23 and 25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11452797.
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims anticipate and/or render obvious the instant claims, as follows:
Regarding claims 1, 5, 18, 23 and 25: Patented claims 1, 2 and 6 renders obvious instant claims 1, 5, 18, 23 and 25. Patented claim 1 requires introduction of a graft into a mammal. The patented claim uses product-by-process limitations to describe how the graft is made. The product-by-process limitations anticipate the active steps of instant claim 1. It would have been prima facie obvious to carry out the product-by-process limitations to first produce the graft, and then implant the graft as required by the patented method. The patented claims also differ in that they are generic to the second cell population being insulin-producing cells, as opposed to islet cells or beta cells. However, patented claim 2 teaches the insulin producing cells are islet cells or beta cells. Finally, regarding the size of the graft, patented claim 6 teaches the size limitation required by instant claim 1.
Regarding claims 2-3: Following the discussion of claim 1 above, patented claims 3-4 teaches the limitations of instant claims 2-3.
Regarding claim 6: Following the discussion of claim 1 above, patented claim 8 teaches the limitation of instant claim 6.
Regarding claims 7 and 15: Following the discussion of claim 1 above, patented claims 10 and 11 teaches the limitations of instant claims 7 and 15, respectively.
Regarding claim 8: Following the discussion of claim 1 above, patented claim 12 teaches the limitations of instant claim 12.
Regarding claim 9: Following the discussion of claim 1 above, patented claim 13 teaches the limitations of instant claim 9.
Regarding claim 10: Following the discussion of claim 1 above, patented claims 13-15 teaches the limitations of instant claim 10.
Regarding claim 11: Following the discussion of claim 1 above, patented claim 16 teaches the limitations of instant claim 11.
Regarding claim 16: Following the discussion of claim 1 above, the insulin producing cells are considered encapsulated within the extracellular matrix.
Regarding claim 17: Following the discussion of claim 1 above, patented claims 11 teaches the limitations of instant claim 17.
Regarding claims 19-22: Following the discussion of claim 1 above, patented claim 16 teaches the alternative cell deliveries covered by claims 19-22.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALLISON M FOX whose telephone number is (571)272-2936. The examiner can normally be reached M-F 10-6 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ALLISON M FOX/Primary Examiner, Art Unit 1633