DETAILED ACTION
Priority
The instant application claims benefit to U. S. Provisional Application 61773888, filed 3/7/2013 (see Supplemental ADS received 12/17/2021). 61773888 provides support for instant claims 1-24; hence, the effective filing date of claims 1-24 is 3/7/2013.
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions because the first inventor to file provisions of the Leahy-Smith America Invents Act (AIA ) apply to applications for patent with an effective filing date on or after March 16, 2013 (see MPEP 35 U.S.C. 100 (note)) whereas the instant claims have an effective filing date of 3/7/2013 which is NOT on or after March 16, 2013.
Status of Application, Amendments, And/Or Claims
The Applicants amendments/remarks received 6/10/2025 are acknowledged. Claim 21 is amended; no claims are canceled; no claims are withdrawn; claims 1-24 are pending and have been examined on the merits.
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 1-24 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 factors to be considered in determining whether undue experimentation is required are summarized in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988) (a) the breadth of the claims; (b) the nature of the invention; (c) the state of the prior art; (d) the level of one of ordinary skill; (e) the level of predictability in the art; (f) the amount of direction provided by the inventor; (g) the existence of working examples; and (h) the quantity of experimentation needed to make or use the invention based on the content of the disclosure. While all of these factors are considered, a sufficient number are discussed below so as to create a prima facie case.
The claims are broadly drawn (factor (a)) to modulating ischemic injury, reducing ischemic injury, increasing the time to ischemic injury in tissues or organs or preserving and/or storing a tissue or organ wherein the tissue or organ can be a donated tissue or organ intended for transplant, epithelial tissue, connective tissue, muscle tissue or nervous tissue, or heart, blood vessel, alimentary canal, stomach, liver, pancreas, spleen, kidney, lung, trachea, cornea, lens, eye, bladder, ureter, urethra, uterus, ovary, testis, nerve, skin, tooth or skeletal muscle by a method of perfusing and/or immersing the tissue or organ with ACCS comprising 5 - 16 ng/mL vascular endothelial growth factor (VEGF), 100 - 165 pg/mL platelet-derived growth factor (PDGF) and 2.5 - 2.7 ng/mL transforming growth factor beta 2 (TGF-β2) wherein the amount of ACCS in the perfusion or immersion solution can be any amount including a de minimus amount and wherein the time of perfusion or immersion can be any length of time including momentary (factors (f) and (g)).
The nature of the invention (factor (b)) is biotechnology, i.e., the physiological arts, which are known to be unpredictable (MPEP 2164.03; factor (e)); however, the skill of the ordinary artisan in such arts is generally high (usually Ph. D. level; factor (d)). Although the claimed method is obvious over the prior art and Applicant’s previous patents as set forth below (factor (c)); Applicant presented evidence in the Remarks received 7/24/2023 that the claimed method WILL NOT modulate ischemic injury, reduce ischemic injury, increase the time to ischemic injury in tissues or organs or preserve a tissue or organ.
Specifically, Applicant argues
“Applicant respectfully submits that one of skill in the art would not practice the methods of Banas substituting the sustained-release ACCS compositions of Marshall for the AMP cell compositions in Banas with a reasonable expectation of success. Applicant directs the Examiner’s attention to the Banas article cited in the April 12, 2022 IDS, “Immunogenicity and immunomodulatory effects of amnion-derived multipotent progenitor cells” (Banas et al., April 2, 2008, Am. Soc. For Histocompatibility and Immunogenetics, vol. 69, 321-328) (hereinafter “Banas 2008”).
“Banas 2008 teaches that conditioned media does not illicit the same immunomodulatory response as AMP cells (Banas 2008, Abstract). Banas 2008 states: “Given that conditioned media from AMP cells were unable to suppress PBMC responses to mitogen, alloantigen, or recall antigen, this finding supports the assertion that cell-to-cell contact is a requirement for the AMP cell immunomodulation.” (Banas 2008, p. 327). As demonstrated in FIG. 3A of Banas 2008, AMP cells diluted 1:5 and placed directly into wells with T cells and mitogen resulted in a proliferative index of around 50%, wherein AMP cell conditioned medium diluted 1:2 had a proliferative index greater than 75% (Banas 2008, p. 326).
“Further, Banas 2008 teaches that in an allogeneic environment in which pro-inflammatory cytokines may be present, e.g., such as during transplant, AMP cells may upregulate PD-1 ligand expression, which in turn may downregulate T-cell activation and proliferation. AMP cells were further described to express the tissue-restricted, nonclassical HLA class I antigen HLA-G, levels of which were low but were upregulated by exposure to IFN-. Banas 2008 goes on to discuss how the immunoregulatory properties of AMP cells and the upregulation of HLA-G after IFN- make them an attractive candidate for potential treatment of diseases that are mediated by T cells, such as transplant rejection. (Banas 2008, p. 327). One of skill in the art would understand that an ACCS composition would not be able to upregulate expression of various genes and would thus not elicit the same anti-inflammatory responses as the AMP cell compositions described in Banas 2008.
“Accordingly, Applicant respectfully traverses this rejection for at least the reasons stated above and submits that the present rejections under § 103 fail to provide a prima facie of obviousness of the pending claims. Applicant requests withdrawal of the present rejections and allowance of all pending claims.” (Remarks, 7/24/2023, pp. 6-7). Thus, Applicant presented evidence that the claimed methods of modulating ischemic injury, reducing ischemic injury, increasing the time to ischemic injury in tissues or organs or preserving a tissue or organ are NOT enabled.
The original disclosure does not provide any non-prophetic working examples of modulating ischemic injury, reducing ischemic injury, increasing the time to ischemic injury in tissues or organs or preserving a tissue or organ with any ACCS composition; nor does the original disclosure provide any details for any methods comprising perfusing or immersing tissues or organs such that no concentrations, or range of concentrations, of ACCS for any perfusion or immersion solution nor time of perfusion effective for reducing ischemia nor procedures for perfusing or immersing the tissues or organs with ACCS to reduce ischemia (factors (f) and (g)) are provided in the original disclosure).
Hence, a person of ordinary skill in the art at the time of filing would have had to engage in undue experimentation (factor (h)) to practice the methods of claims 1-24, if they are enabled at all; therefore, claims 1-24 are rejected under 35 U.S.C. 112(a) for not being enabled commensurate in scope with the claims.
Response to Arguments
Applicant's arguments filed 6/10/2025 have been fully considered but they are not persuasive. Regarding the rejection of claims 1-24 under 35 U.S.C. § 112(a), Applicant alleges (pp. 6-7) that the factors set forth in In Re Wands have not been considered on the record. This is incorrect, the Wands factors were considered. In order to assist Applicant in following the consideration, the Wands factors have been explicitly noted in the rejection above.
Applicant notes that “Enablement can be satisfied by a clear and complete description, especially where the methods and compositions are well-known and routine in the art. The Federal Circuit has repeatedly held that prophetic examples and detailed protocols can suffice where undue experimentation is not required (see, e.g., In re Wright, 999 F.2d 1557, 1562-63 (Fed. Cir. 1993)).” (p. 8). No detailed protocols or complete descriptions for perfusing or immersing tissues or organs in such a manner that ischemia is reduced are disclosed in the original disclosure. No effective concentrations, or ranges of concentrations, of ACCS are given; no effective perfusion or immersion solutions are provided, nor are any detailed protocols given, nor times of perfusion or immersion which are effective for reducing ischemic injury; hence, the claims fail to be enabled for the scope of the claims because no enabling disclosure is provided; hence, practicing the claimed methods for the scope of the claimed inventions would clearly require undue experimentation.
Applicant appears to allege (pp. 8-9) that reducing ischemic injury in tissues or organs by perfusion or immersion with ACCS is well-known and routine in the art, but does not point to any prior art disclosing the concentration of ACCS in the perfusion solution; which perfusion solution comprising ACCS is effective or the methodology and time of perfusion which is effective; hence, Applicant’s allegation that the method is enabled because it is well-known and routine in the art does not make up for the obvious deficiencies of the original disclosure; hence, the rejection is maintained.
Claim Rejections - 35 USC § 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 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 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 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.
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 1-24 are rejected under 35 U.S.C. 103 as being unpatentable over Banas et al., US 2012/0052045 (US Patent Application Publication cite 1, IDS, 4/12/2022; herein “Banas”) in view of Palladino et al., US 2009/0010899 (cite A, attached PTO-892; herein “Palladino”).
Banas teaches methods of modulating or reducing ischemic injury and increasing the time to ischemic injury in donor tissues and organs harvested for transplantation (Abst.; [0011-16]) by contacting the tissues or organs with compositions comprising Amnion-derived Multipotent Progenitor cells (AMP cells) or membrane extracts of AMP cells ([0012], [0019, [0036-38], claims 4 and 5). Banas teaches that the administration of the compositions can be by perfusion [0013] and that the organ can be a heart [0020], i.e., muscle tissue. Banas teaches that their method is for storing harvested organs [0011]. Banas teaches that the AMP cell and membrane extract compositions have been found to suppress inflammatory responses in small amounts which prevents, modulates or reduces the ischemic injury resultant from the inflammatory response [0076-78].
Banas does not teach that the compositions for reducing ischemic injury comprise Amnion-derived Cellular Cytokine Solution (ACCS) wherein the ACCS comprises 5 - 16 ng/mL vascular endothelial growth factor (VEGF), 100 - 165 pg/mL platelet-derived growth factor (PDGF), and 2.5 - 2.7 ng/mL transforming growth factor beta 2 (TGF-β2). However, a person of ordinary skill in the art at the time of filing would have found it obvious that the compositions for reducing ischemic injury to tissues or organs can comprise ACCS, comprising 5 - 16 ng/mL VEGF, 100 - 165 pg/mL PDGF and 2.5 - 2.7 ng/mL TGF-β2, instead of AMP cells because Palladino teaches AMP cell compositions and ACCS compositions are functionally equivalent.
Palladino teaches accelerating healing of anastomoses in tissues comprising contacting the tissues with compositions comprising AMP cells or ACCS, either alone or in combination (Abst.; [0002], [0008], [0027], [0034], [0072-74], [0077-80], [0083], [0088-96], [0102]); hence, Palladino teaches that compositions comprising AMP cells and compositions comprising ACCS are functionally equivalent. Palladino teaches that ACCS can comprise 5 - 16 ng/mL VEGF, 100 - 165 pg/mL PDGF and 2.5 - 2.7 ng/mL TGF-β2 [0071]. Palladino teaches that the ACCS compositions can be sustained-release formulations [0079], i.e., extended release. Hence, a person of ordinary skill in the art at the time of the invention would have found it obvious to practice the methods of Banas substituting the functionally equivalent sustained-release ACCS compositions of Palladino, comprising 5 - 16 ng/mL VEGF, 100 - 165 pg/mL PDGF and 2.5 - 2.7 ng/mL TGF-β2, for the AMP cell compositions in Banas with a reasonable expectation of success because Palladino teaches that the ACCS compositions and AMP cell compositions are functionally equivalent.
Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the organ preservation method made obvious by Banas in view of Palladino comprising perfusing donated heart with sustained release ACCS comprising 5 - 16 ng/mL VEGF, 100 - 165 pg/mL PDGF and 2.5 - 2.7 ng/mL TGF-β2 wherein the ACCS composition does not comprise amnion-derived multipotent cells because Banas teaches an organ preservation method comprising perfusing donated heart with AMP cells and Palladino teaches ACCS compositions and AMP cell compositions are functionally equivalent, teaches ACCS can comprise 5 - 16 ng/mL VEGF, 100 - 165 pg/mL PDGF and 2.5 - 2.7 ng/mL TGF-β2 and teaches ACCS compositions can be formulated for sustained release; therefore, claims 1-24 are prima facie obvious.
Response to Arguments
Applicant has provided a submission in this file (Remarks received 6/10/2025, p. 6) that the claimed invention and the subject matter disclosed in the prior art reference (Banas et al., US 2012/0052045) were owned by, or subject to an obligation of assignment to, the same entity (Noveome Biotherapeutics, Inc., formerly Stemnion, Inc.) as the instant invention not later than the effective filing date of the claimed invention.
Applicant asserts that “Because of the continued common ownership of Banas and present application; Banas falls into the prior art exception of 35 U.S.C. § 102(b)(2)(C). Applicant submits that this section is a statement of common ownership sufficient to disqualify Banas as prior art under 35 U.S.C. § 102(b)(2)(C), as it is fully compliant with MPEP § 717 .02(b)(Ill).”
This is unpersuasive because the instant application has an effective filing date of 3/7/2013 (see Supplemental ADS received 12/17/2021 and p. 2 above) which is NOT on or after March 16, 2013; hence, the provisions of the AIA do not apply. Thus, the present application is being examined under the pre-AIA first to invent provisions (see discussion on p. 2 above). The prior art exception of 35 U.S.C. § 102(b)(2)(C) does not apply to pre-AIA applications.
However, even if the application had an effective filing date on or after March 16, 2013 and was being examined under the provisions of the AIA , Banas et al., US 2012/0052045 would still constitute prior art because Banas et al., US 2012/0052045 was published 3/1/2012 which is greater than 1 year before the effective filing date of the instant invention; thus, Banas et al., US 2012/0052045 would be prior art under 35 U.S.C. 102(a)(1) whereas the prior art exception of 35 U.S.C. § 102(b)(2)(C) only disqualifies prior art under 35 U.S.C. 102(a)(2) and does not disqualify prior art under 35 U.S.C. 102(a)(1) (see MPEP 717.02(b)(II)). Banas et al., US 2012/0052045 constitutes prior art and would still constitute prior art if the instant application were being examined under the provisions of the AIA . Thus, Applicant’s assertion that Banas et al., US 2012/0052045 is disqualified as prior art is incorrect and the rejection is maintained.
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, 3-6, 8-11, 13-16 and 18-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 6-7 and 9 of U.S. Patent No. 9574177 (herein “’177”) in view of Banas.
Claim 6 of ‘177 recites a method of protecting a population of cells at risk for developing excessive cellular apoptosis, the method comprising the step of contacting the population of cells at risk for developing excessive cellular apoptosis with a therapeutically effective dose of a composition selected from the group consisting of ACCS and AMP cells, such that the cells are protected from developing excessive cellular apoptosis; claim 7 of ‘177 recites the method of claim 6 wherein the ACCS comprises physiologic concentrations of VEGF, TGFβ2, Angiogenin, PDGF, TIMP-1 and TIMP-2, wherein the physiologic concentration is about 5.0-16 ng/mL for VEGF, about 3.5-4.5 ng/mL for Angiogenin, about 100-165 pg/mL for PDGF, about 2.5-2.7 ng/mL for TGFβ2, about 0.68 g/mL for TIMP-1, and about 1.04 ug/mL for TIMP-2; and claim 9 of ‘177 recites the method of claim 6 wherein the protecting of cells from excessive cellular apoptosis occurs in a donated organ or tissue.
Hence, ‘177 teaches the functional equivalence of AMP cell compositions and ACCS and teaches methods of contacting tissues or organs with compositions comprising ACCS comprising 5.0-16 ng/mL for VEGF, about 100-165 pg/mL for PDGF and about 2.5-2.7 ng/mL for TGFβ2. The claims of ‘177 does not teach perfusing the tissues or organs with the compositions or that the organ can be heart; however, a person of ordinary skill in the art at the time of filing would have found it obvious for the contacting to be perfusion and for the organ to be heart in view of Banas.
Banas teaches methods of modulating or reducing ischemic injury and increasing the time to ischemic injury in donor tissues and organs harvested for transplantation (Abst.; [0011-16]) by contacting the tissues or organs with compositions comprising Amnion-derived Multipotent Progenitor cells (AMP cells) or membrane extracts of AMP cells ([0012], [0019, [0036-38], claims 4 and 5). Banas teaches that the administration of the compositions can be by perfusion [0013] and that the donor organ can be a heart [0020], i.e., muscle tissue. Banas teaches that their method is for storing harvested organs [0011]. Banas teaches that the AMP cell and membrane extract compositions have been found to suppress inflammatory responses in small amounts which prevents, modulates or reduces the ischemic injury resultant from the inflammatory response [0076-78].
Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method made obvious by claims 6-7 and 9 of ‘177 in view of Banas comprising perfusing donated heart with ACCS comprising 5 - 16 ng/mL VEGF, 100 - 165 pg/mL PDGF and 2.5 - 2.7 ng/mL TGF-β2 wherein the ACCS composition does not comprise amnion-derived multipotent cells because claims 6-7 and 9 of ‘177 teach contacting donated organs with ACCS comprising 5 - 16 ng/mL VEGF, 100 - 165 pg/mL PDGF and 2.5 - 2.7 ng/mL TGF-β2, teaches ACCS compositions and AMP cell compositions are functionally equivalent and Banas teaches an organ preservation method comprising perfusing donated heart; therefore, instant claims 1, 3-6, 8-11, 13-16 and 18-20 are prima facie obvious over claims 6-7 and 9 of ‘177 in view of Banas.
Claims 1-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 6-7 and 9 of U.S. Patent No. 9574177 (herein “’177”) in view of Banas and claims 1 and 5 of U.S. Patent No. 8058066 (herein “’066”).
The discussion of claims 6-7 and 9 of U.S. Patent No. 9574177 (herein “’177”) in view of Banas regarding instant claims 1, 3-6, 8-11, 13-16 and 18-20 set forth in the rejection above is incorporated herein.
Neither claims 6-7 and 9 of U.S. Patent No. 9574177 (herein “’177”) nor Banas teach that the ACCS compositions are sustained release, i.e., extended-release; however, a person of ordinary skill in the art at the time of filing would have found it obvious for the ACCS compositions to be sustained release compositions in view of claims 1 and 5 of ‘066.
Claim 1 of ‘066 recites a method of making a pooled amnion-derived cellular cytokine solution (ACCS) comprising the proteins VEGF, Angiogenin, PDGF, TGFβ2, TIMP-1 and TIMP-2, wherein the proteins levels are ~5.0-16 ng/mL for VEGF, ~3.5-4.5 ng/mL for Angiogenin, ~100-165 pg/mL for PDGF, -2.5-2.7 ng/mL for TGFβ2, -0.68 µg/mL for TIMP-1 and ~ 1.04 µg/mL for TIMP-2, the method comprising the steps of:
a) obtaining a placenta and isolating the amnion from the placenta,
b) enzymatically releasing amnion-derived epithelial cells from the amnion,
c) collecting the released amnion-derived epithelial cells, and
d) culturing the collected amnion-derived epithelial cells of step (c) in a tissue culture vessel for about 2 days in basal culture medium that does not contain any non-human animal protein and is, optionally, further supplemented with recombinant human protein factors capable of stimulating proliferation of the cultured amnion-derived epithelial cells,
e) selecting amnion-derived multipotent progenitor (AMP) cells from the amnion-derived epithelial cells of step (d) by removing and discarding the culture medium which contains cells that have not attached to the tissue culture vessel and keeping the cells that have attached to the tissue culture vessel, such attached cells consisting essentially of AMP cells,
f) culturing the selected AMP cells of step (e) in basal culture medium that does not contain any non-human animal protein and is, optionally, further supplemented with recombinant human protein factors capable of stimulating proliferation of the cultured AMP cells until they reach confluence,
g) removing the culture medium from the confluent AMP cells in step (f) and culturing the confluent AMP cells as with fresh culture medium and culturing the AMP cells for 1, 2, 3, 4, 5, or 6 days,
h) collecting the culture medium of step (g) to obtain ACCS and adding fresh medium to the confluent AMP cells, and
i) repeating steps (g) and (h) a plurality of times and combining the ACCS obtained in each step (h) to create the pooled ACCS; and claim 5 of ‘066 recites the method of claim 1 which further comprises the step of
j) adding an agent capable of effecting sustained-release of the pooled ACCS.
Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method made obvious by claims 6-7 and 9 of ‘177 in view of Banas wherein the ACCS composition is a sustained release ACCS composition; therefore, claims 1-24 are prima facie obvious over claims 6-7 and 9 of ‘177 in view of Banas and claims 1 and 5 of ‘066.
Claims 1, 3-6, 8-11, 13-16 and 18-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of U.S. Patent No. 8642027 (herein “’027”) in view of claims 6-7 and 9 of U.S. Patent No. 9574177 (herein “’177”).
Claim 1 of ‘027 recites a method for reducing ischemic injury in tissues or organs that have been harvested for organ transplant comprising the step of perfusing the harvested tissue or organ with a composition comprising Amnion-derived Multipotent Progenitor (AMP) cells; and claim 2 of ‘027 recites a method for increasing the time to ischemic injury in tissues or organs that have been harvested for organ transplant comprising the step of perfusing the tissue or organ with a composition comprising Amnion-derived Multipotent Progenitor (AMP) cells.
Consultation of the specification for the metes and bounds of “organ” (see MPEP 804(II)(B)(1) “The portion of the specification of the reference that describes subject matter that falls within the scope of a reference claim may be relied upon to properly construe the scope of that claim”) discloses that heart is encompassed by “organ” (col. 3, ll. 33-35).
Claims 1 and 2 of ‘027 teach methods for reducing ischemic injury in harvested (i.e., donated) tissues or organs and increasing the time to ischemic injury in harvested (i.e., donated) tissues or organs by perfusing the tissue or organ with AMP cells, but claims 1 and 2 does not disclose perfusing the organs with ACCS comprising 5.0-16 ng/mL for VEGF, about 100-165 pg/mL for PDGF and about 2.5-2.7 ng/mL for TGFβ2; however, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the methods of claims 1 and 2 of ‘027 wherein the organ is perfused with ACCS comprising 5.0-16 ng/mL for VEGF, about 100-165 pg/mL for PDGF and about 2.5-2.7 ng/mL for TGFβ2 in view of claims 6-7 and 9 of ‘177.
Claim 6 of ‘177 recites a method of protecting a population of cells at risk for developing excessive cellular apoptosis, the method comprising the step of contacting the population of cells at risk for developing excessive cellular apoptosis with a therapeutically effective dose of a composition selected from the group consisting of ACCS and AMP cells, such that the cells are protected from developing excessive cellular apoptosis; claim 7 of ‘177 recites the method of claim 6 wherein the ACCS comprises physiologic concentrations of VEGF, TGFβ2, Angiogenin, PDGF, TIMP-1 and TIMP-2, wherein the physiologic concentration is about 5.0-16 ng/mL for VEGF, about 3.5-4.5 ng/mL for Angiogenin, about 100-165 pg/mL for PDGF, about 2.5-2.7 ng/mL for TGFβ2, about 0.68 g/mL for TIMP-1, and about 1.04 ug/mL for TIMP-2; and claim 9 of ‘177 recites the method of claim 6 wherein the protecting of cells from excessive cellular apoptosis occurs in a donated organ or tissue.
Hence, ‘177 teaches the functional equivalence of AMP cell compositions and ACCS and teaches methods of contacting tissues or organs with compositions comprising ACCS comprising 5.0-16 ng/mL for VEGF, about 100-165 pg/mL for PDGF and about 2.5-2.7 ng/mL for TGFβ2.
Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method made obvious by claims 1-2 of ‘027 in view of claims 6-7 and 9 of ‘177 comprising perfusing donated heart with ACCS comprising 5 - 16 ng/mL VEGF, 100 - 165 pg/mL PDGF and 2.5 - 2.7 ng/mL TGF-β2 wherein the ACCS composition does not comprise amnion-derived multipotent cells because claims 1-2 of ‘027 teach methods for reducing ischemic injury in harvested (i.e., donated) tissues or organs and increasing the time to ischemic injury in harvested (i.e., donated) tissues or organs, wherein the organ can be heart, by perfusing the tissue or organ with AMP cells, claims 6-7 and 9 of ‘177 teaches ACCS compositions and AMP cell compositions are functionally equivalent and teaches contacting donated organs with ACCS comprising 5 - 16 ng/mL VEGF, 100 - 165 pg/mL PDGF and 2.5 - 2.7 ng/mL TGF-β2; therefore, instant claims 1, 3-6, 8-11, 13-16 and 18-20 are prima facie obvious over claims 1-2 of ‘027 in view of claims 6-7 and 9 of ‘177.
Claims 1-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of ’027 in view of claims 6-7 and 9 of ’177 and claims 1 and 9 of U.S. Patent No. 8530418 (herein “’418”).
The discussion of claims 1-2 of ‘027 and claims 6-7 and 9 of ’177 regarding instant claims 1, 3-6, 8-11, 13-16 and 18-20 set forth in the rejection above is incorporated herein.
Neither claims 1-2 of ‘027 nor claims 6-7 and 9 of ’177 teach that the ACCS compositions are sustained release, i.e., extended-release; however, a person of ordinary skill in the art at the time of filing would have found it obvious for the ACCS compositions to be sustained release compositions in view of claims 1 and 9 of ‘418.
Claim 1 of ‘418 recites a composition comprising a pooled amnion-derived cellular cytokine Solution (ACCS) comprising the proteins VEGF, Angiogenin, PDGF, TGFB2, TIMP-1 and TIMP-2, wherein the proteins levels are ~5.0-16 ng/mL for VEGF, ~3.5-4.5ng/mL for Angiogenin, ~100-165 pg/mL for PDGF, ~2.5-2.7 ng/mL for TGFβ2, ~0.68 g/mL for TIMP-1 and ~1.04 ug/mL for TIMP-2, the composition made by a method comprising the steps of
a) obtaining a placenta and isolating the amnion from the placenta,
b) enzymatically releasing amnion-derived epithelial cells from the amnion,
c) collecting the released amnion-derived epithelial cells, and
d) culturing the collected amnion-derived epithelial cells of step (c) in a tissue culture vessel for about 2 days in basal culture medium that does not contain any non-human animal protein and is, optionally, further supplemented with recombinant human protein factors capable of stimulating proliferation of the cultured amnion-derived epithelial cells,
e) selecting amnion-derived multipotent progenitor (AMP) cells from the amnion-derived epithelial cells of step (d) by removing and discarding the culture medium which contains cells that have not attached to the tissue culture vessel and keeping the cells that have attached to the tissue culture vessel. Such attached cells consisting essentially of AMP cells,
f) culturing the selected AMP cells of step (e) in basal culture medium that does not contain any non-human animal protein and is, optionally, further supplemented with recombinant human protein factors capable of stimulating proliferation of the cultured AMP cells until they reach confluence,
g) removing the culture medium from the confluent AMP cells in step (f) and culturing the confluent AMP cells with fresh culture medium and culturing the AMP cells for 1, 2, 3, 4, 5, or 6 days,
h) collecting the culture medium of step (g) to obtain ACCS and adding fresh medium to the confluent AMP cells, and
i) repeating steps (g) and (h) a plurality of times and combining the ACCS obtained in each step (h) to create the pooled ACCS; and claim 9 of ‘418 recites the composition of claim 1 which is further processed by the step of adding an agent capable of effecting sustained release.
Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method made obvious by claims 1-2 of ‘027 in view of claims 6-7 and 9 of ‘177 wherein the ACCS composition is a sustained release ACCS composition; therefore, claims 1-24 are prima facie obvious over claims 1-2 of ‘027 in view of claims 6-7 and 9 of ‘177 and claims 1 and 9 of ‘418.
Claims 1-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of ‘027 in view of Palladino.
Claim 1 of ‘027 recites a method for reducing ischemic injury in tissues or organs that have been harvested for organ transplant comprising the step of perfusing the harvested tissue or organ with a composition comprising Amnion-derived Multipotent Progenitor (AMP) cells; and claim 2 of ‘027 recites a method for increasing the time to ischemic injury in tissues or organs that have been harvested for organ transplant comprising the step of perfusing the tissue or organ with a composition comprising Amnion-derived Multipotent Progenitor (AMP) cells.
Consultation of the specification for the metes and bounds of “organ” (see MPEP 804(II)(B)(1) “The portion of the specification of the reference that describes subject matter that falls within the scope of a reference claim may be relied upon to properly construe the scope of that claim”) discloses that heart is encompassed by “organ” (col. 3, ll. 33-35).
Claims 1 and 2 of ‘027 teach methods for reducing ischemic injury in harvested (i.e., donated) tissues or organs and increasing the time to ischemic injury in harvested (i.e., donated) tissues or organs by perfusing the tissue or organ with AMP cells, but claims 1 and 2 does not disclose perfusing the organs with ACCS comprising 5.0-16 ng/mL for VEGF, about 100-165 pg/mL for PDGF and about 2.5-2.7 ng/mL for TGFβ2; however, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the methods of claims 1 and 2 of ‘027 wherein the organ is perfused with ACCS comprising 5.0-16 ng/mL for VEGF, about 100-165 pg/mL for PDGF and about 2.5-2.7 ng/mL for TGFβ2 in view of Palladino because Palladino teaches AMP cell compositions and ACCS compositions are functionally equivalent.
Palladino teaches accelerating healing of anastomoses in tissues comprising contacting the tissues with compositions comprising AMP cells or ACCS, either alone or in combination (Abst.; [0002], [0008], [0027], [0034], [0072-74], [0077-80], [0083], [0088-96], [0102]); hence, Palladino teaches that compositions comprising AMP cells and compositions comprising ACCS are functionally equivalent. Palladino teaches that ACCS can comprise 5 - 16 ng/mL VEGF, 100 - 165 pg/mL PDGF and 2.5 - 2.7 ng/mL TGF-β2 [0071]. Palladino teaches that the ACCS compositions can be sustained-release formulations [0079], i.e., extended release. Hence, a person of ordinary skill in the art at the time of the invention would have found it obvious to practice the methods of Banas substituting the functionally equivalent sustained-release ACCS compositions of Palladino, comprising 5 - 16 ng/mL VEGF, 100 - 165 pg/mL PDGF and 2.5 - 2.7 ng/mL TGF-β2, for the AMP cell compositions in Banas with a reasonable expectation of success because Palladino teaches that the ACCS compositions and AMP cell compositions are functionally equivalent.
Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the organ preservation methods made obvious by claims 1-2 of ‘027 in view of Palladino comprising perfusing donated heart with sustained release ACCS comprising 5 - 16 ng/mL VEGF, 100 - 165 pg/mL PDGF and 2.5 - 2.7 ng/mL TGF-β2 wherein the ACCS composition does not comprise amnion-derived multipotent cells because claims 1-2 of ‘027 teach reducing ischemic injury in harvested (i.e., donated) tissues or organs and increasing the time to ischemic injury in harvested (i.e., donated) tissues or organs by perfusing the tissue or organ with AMP cells and Palladino teaches ACCS compositions and AMP cell compositions are functionally equivalent, teaches ACCS can comprise 5 - 16 ng/mL VEGF, 100 - 165 pg/mL PDGF and 2.5 - 2.7 ng/mL TGF-β2 and teaches ACCS compositions can be formulated for sustained release; therefore, claims 1-24 are prima facie obvious.
Response to Arguments
Regarding the rejections on the ground of nonstatutory double patenting, Applicant states (Remarks, p. 11) “Applicant respectfully traverses this rejection, which in light of the amendments to the claims Applicant also considers moot. Should any claims be allowed in either application, Applicant will address any remaining rejections at that time. Thus, without admitting the propriety of the rejection and in the interest of furthering prosecution, Applicants hereby notify the Office that a terminal disclaimer, listing U.S. Patent No. 9,574,177, will be submitted upon allowance of pending claims 1, 3-6, 8-11, 13-16, and 18-20, should it be necessary.” The instant amended claims do not significantly change the subject matter of the claims and the reference patents are all patents, not co-pending Applications; hence, it is unclear why Applicant would allege that the rejections are moot in light of the claim amendments or why Applicant would refer to “either application”. Regardless, the rejections are maintained.
FYI: disqualification of prior art under 35 U.S.C. 102(b)(2)(C) does not remove the art from being used in nonstatutory double patenting rejections (see MPEP 717.02(b)(II)); hence, even if the instant application were being examined under the provisions of the AIA and even if Banas et al., US 2012/0052045 had successfully been disqualified as prior art under 35 U.S.C. 102(b)(2)(C), it would still be appropriate to use Banas et al., US 2012/0052045 as the basis for nonstatutory double patenting rejections.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/TRENT R CLARKE/Examiner, Art Unit 1651
/DAVID W BERKE-SCHLESSEL/Primary Examiner, Art Unit 1651