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 .
Amendment
In the reply filed on 01/12/2026, Applicant has canceled claims 80-136.
Election/Restriction
Applicant’s election of Group I, claims 1-4, 20-22, 28-30, 35-36, 43-46, 51-52, 63 and 75, drawn to a method of treating or preventing ED by administering a composition comprising fibroblasts and/or conditioned media, in the reply filed on 01/12/2026, is acknowledged.
Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.03(a)).
The requirement is still deemed proper and is therefore made FINAL.
In the reply filed on 01/12/2026, Applicant further elects the species of procedure to obtain regenerative fibroblast cells in claims 28-29 and the species of therapies sufficient to stimulate committed EPCs to enter the peripheral blood in claim 52.
Claims 3, 30, 35-36 and 51 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
Claim Status
Claims 1-4, 20-22, 28-30, 35-36, 43-46, 51-52, 63 and 75 are pending.
Claims 3, 30, 35-36 and 51 are withdrawn.
Claims 1-2, 4, 20-22, 28-29, 43-46, 52, 63 and 75 are considered on the merits.
Priority
This application is a 371 of PCT/US2021/026752 (filed on 04/10/2021), which claims benefit from application 63/008,970 (filed on 04/13/2020). The priority claim of the instant application has been granted and the earliest benefit date is 04/13/2020 from the application 63/008,970.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 10/12/2022 and 01/27/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner. The corresponding signed and initialed PTO forms 1449 have been mailed with this action.
Claim Objections
Claim 52 is objected to because of the following informalities:
Claim 52 recites the limitation of one or more therapies sufficient to stimulate committed endothelial progenitor cells from “the individual” to enter the peripheral blood. However, the base claims 45, 44, 43 and 1 only recite a committed endothelial progenitor cell (EPC) population is administered in combination with the fibroblast cells to “an individual in need thereof”. In other words, the base claims recite the EPCs are administered to an individual, but not stimulated from the individual. The limitation in claim 52 seems to be in a similar pattern as the limitation in the withdrawn claim 51, and is thus examined as “The method of claim 45, wherein the committed endothelial progenitor cells are isolated from peripheral blood of an individual who has been exposed to one or more therapies sufficient to stimulate committed endothelial progenitor cells from the individual to enter the peripheral blood comprise therapies including …”.
Appropriate correction is required.
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.
Claim 22 is 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.
Claim 22 recites the limitation the cells have “enhanced GDF-11 expression compared to a control or standard”. Applicant is reminded that a claim may be rendered indefinite by reference to term of an object that is variable (see MPEP 2173.05(b), II). Specifically, the phrase “enhanced … compared to a control or standard” is a relative term which renders the claim indefinite. The “control or standard” is not defined by the claim, the specification does not provide a control or standard for ascertaining the requisite baseline, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Since no control or standard is provided, the limitation is examined as “the regenerative fibroblast cells have GDF-11 expression”.
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 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 1-2, 4, 63 and 75 are rejected under 35 U.S.C. 103 as being unpatentable over Yang et al., (Andrology, 2018, 6, 498-509) in view of Ichim et al., (J Transl Med. 2018;16:212, p. 1-9. Cited in IDS 10/12/2022) and Ohara et al., (Gene Therapy. 2001;8: 837-845).
With respect to claim 1, Yang teaches a method of treating erectile dysfunction in an individual (i.e., in aged rat models, see e.g., title and abstract). Yang teaches 200 µL PBS solution containing 5 x 105 adipose-derived stem cells (ADSCs) was injected into the corpora cavernosum in the treatment group (p. 499, right col, para 4), thus teaches the method comprises the step of administering a therapeutically effective amount of a composition comprising cells (e.g., ADSCs) to an individual in need thereof. Yang teaches that ADSC treatment improves aging-related ED through the secretion of IGF-1, bFGF, and VEGF (e.g., abstract, also see Fig 3).
However, Yang is silent on the cells being fibroblasts in claim 1, regenerative fibroblasts in claim 2, the biological activities of induction of angiogenesis in claim 4 or a composition comprising regenerative fibroblast-conditioned media in claim 75.
In regard to using fibroblasts as a practical alternative to mesenchymal stem cells (such as ADSCs), Ichim summarizes that fibroblasts are easily harvested in large numbers from various biological wastes and additionally, in vitro expansion of fibroblasts is significantly easier given the robustness of these cells in tissue culture and shorter doubling time compared to typical MSC (e.g., abstract). Ichim suggests the concept that fibroblasts may be utilized as a more practical, and potentially more effective cell therapy than mesenchymal stem cells because of their anti-inflammatory, immune modulatory, and regenerative properties (e.g., abstract).
Ohara teaches a method of promoting collateral vessel formation comprising administering a composition comprising bFGF-transduced fibroblasts to a rabbit model of hindlimb ischemia (see e.g., abstract, it is noted that bFGF is also known as FGF-2), thus teaches administering fibroblasts, related to claim 1.
In regard to regenerative fibroblasts, the instant specification recites "regenerative" refers to the ability of fibroblasts to effect therapeutic functions, production of growth factors (such as FGF-2), and stimulation of angiogenesis, and fibroblasts having regenerative activities can be isolated and subsequently transfected with genes capable of endowing therapeutic functions ([0046]). Accordingly, the bFGF-transduced fibroblasts of Ohara qualifies as regenerative fibroblasts because they have the ability to effect therapeutic functions, produce growth factors such as FGF-2 and stimulate angiogenesis (see e.g., Fig 5 and Fig 1), related to claim 2 and claim 4.
In regard to the regenerative fibroblast-conditioned media, Ohara teaches the bFGF-transduced fibroblasts secret bFGF into the culture medium (see e.g., p. 838, left col, para “In vitro study”, and Fig 1C), and teaches the conditioned medium of the secretory group is added to testing fibroblasts and the uptake of 3H-thymidine by the testing fibroblasts is significantly increased than those exposed to the conditioned medium from the native group (e.g., p. 838, right col, para 1, see Fig 1e), thus teaches regenerative fibroblast-conditioned media, related to claim 75.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of treating erectile dysfunction by administering bFGF-secreting ADSCs disclosed by Yang, by substituting the ADSCs with bFGF-secreting fibroblasts as suggested by Ichim and Ohara with a reasonable expectation of success. Since Yang teaches that ADSC treatment improves aging-related ED through the secretion of growth factors such as bFGF (e.g., abstract, also see Fig 3), since Ichim suggests that fibroblasts may be utilized as a more practical and potentially more effective cell therapy than mesenchymal stem cells (such as ADSCs) because of their easy harvest and expansion and their anti-inflammatory, immune modulatory, and regenerative properties (e.g., abstract), and since Ohara reduces to practice administering bFGF-transduced fibroblasts that secret growth factors such as bFGF to stimulate angiogenesis (see e.g., Fig 1 and Fig 5), one of ordinary skill in the art would have had a reason to substitute the mesenchymal stem cells (i.e., ADSCs) of Yang with the bFGF-secreting fibroblasts as suggested by Ichim and Ohara in order to take advantage of the easy harvest and expansion of fibroblasts and also their secretion of bFGF and stimulation of angiogenesis to treat ED as recited in claims 1, 2 and 4.
Furthermore, Yang assays the conditioned medium from ADSCs that comprises growth factors such as bFGF (e.g., Figs 2-3) and acknowledges that the conditioned media comprising exosomes secreted by ADSCs can be used to treat ED (p. 507, right col, para 2). Ohara teaches the conditioned medium of the bFGF-secreting fibroblasts comprises bFGF and increases proliferation of fibroblasts (e.g., see Fig 1C and 1e).
Accordingly, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have chosen the conditioned medium of the bFGF-secreting fibroblasts (i.e., the regenerative fibroblast-conditioned media) of Ohara in the method of treating ED as suggested by Yang with a reasonable expectation of success. One of the ordinary skill in the art would have had a reason to choose administering conditioned media in order to reduce the potential side effects related to cell therapy (e.g., immunosuppressive capacity, see Ichim p. 4, right col, section “immune modulation”), as recited in claim 75.
With respect to claim 63 directed to the erectile dysfunction comprising vascular insufficiency, Yang teaches aging-related erectile dysfunction involves endothelial dysfunction and veno-occlusive dysfunction (p. 498, section “Introduction”, para 1) and has reduced intracavernosal pressure (see e.g., Fig 4), thus teaches the erectile dysfunction comprises vascular insufficiency.
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Yang et al., (Andrology, 2018, 6, 498-509) in view of Ichim et al., (J Transl Med. 2018;16:212, p. 1-9. Cited in IDS 10/12/2022) and Ohara et al., (Gene Therapy. 2001;8: 837-845), as applied to claims 2 and 1 above, and further evidenced by Stavri et al., (Circulation. 1995; 92(1): 11-14).
Claim 20 is directed to the regenerative fibroblast cells expressing c-Myc.
Stavri acknowledges that bFGF stimulates endothelial cell proliferation in vitro and angiogenesis in vivo and in addition, it has mitogenic activity in other cells, including VSMCs and fibroblasts (p. 2, para 1). Stavri evidences that bFGF treatment increases c-Myc expression in exemplary VSMCs (p. 3, “Results” para 1, also see Fig 1A).
Accordingly, one of ordinary skill in the art before the effective filing date of the claimed invention would have immediately expected that the bFGF-secreting fibroblasts of Yang in view of Ichim and Ohara, would have likely expressed c-Myc since Stavri evidences that bFGF has mitogenic activity on VSMCs and fibroblasts and bFGF treatment increases c-Myc expression in exemplary VSMCs (see above).
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Claims 21 and 28-29 are rejected under 35 U.S.C. 103 as being unpatentable over Yang et al., (Andrology, 2018, 6, 498-509) in view of Ichim et al., (J Transl Med. 2018;16:212, p. 1-9. Cited in IDS 10/12/2022) and Ohara et al., (Gene Therapy. 2001;8: 837-845), as applied to claims 2 and 1 above, and further in view of Kim et al., (Tissue Eng Regen Med. 2019; 16(1): 59-68) and Baksh et al., (Blood. 2005;106:3012-3019).
Claims 28-29 are directed to the regenerative fibroblast cells being isolated from peripheral blood of an individual who has been administered G-CSF or GM-CSF to stimulate entering the peripheral blood. Claim 21 is directed to the regenerative fibroblast cells not expressing CD45.
Ohara teaches the fibroblasts are cultured from the resected skin tissue (p. 843, last para.).
However, Yang, Ichim and Ohara are silent on the regenerative fibroblast cells being isolated from peripheral blood of an individual who has been administered G-CSF to stimulate entering the peripheral blood in claims 28-29, nor teaches the regenerative fibroblast cells not expressing CD45 in claim 21.
Kim teaches GM-CSF and G-CSF mobilize colony-forming unit–fibroblast (CFU-F) cells from bone marrow to peripheral blood (see e.g., p. 62, right col, para 2, and p. 63, para 1, also see CFU-F assay on mononuclear cells isolated from peripheral blood in Fig 1C and Fig 2B). Thus, Kim teaches the fibroblast cells (i.e., CFU-fibroblast cells) are isolated from peripheral blood of an individual who has been administered GM-CSF or G-CSF (p. 60, right col, para 2.1) to stimulate the fibroblast cells to enter the peripheral blood, related to claims 28-29.
Baksh teaches CD45+ cells demonstrated no capacity to form CFU-Fs (Figure 3Cii) (p. 3015, right col, para 3) and the cells harvested from the CD45+ suspension cultures did not give rise to CFU-Fs and CFU-Os (Fig 3C legend), thus teaches CFU-F cells do not express CD45, related to claim 21.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of treating ED by administering bFGF-transduced fibroblasts that are cultured from resected skin tissue as suggested by Yang in view of Ichim and Ohara, by substituting the step of culturing fibroblasts from resected skin tissue with isolating fibroblasts (CFU-fibroblast cells) from peripheral blood after mobilization with GM-CSF or G-CSF as suggested by Kim with a reasonable expectation of success. Since Kim reduces to practice the steps of isolating fibroblasts (i.e., CFU-fibroblast cells) from peripheral blood following GM-CSF or G-CSF mobilization, one of ordinary skill in the art would have had a reason to substitute with isolating fibroblasts from peripheral blood as suggested by Kim in order to minimize the invasive procedure related to resecting skin tissue by Ohara.
Furthermore, one of ordinary skill in the art before the effective filing date of the claimed invention would have immediately expected that the fibroblasts (i.e., CFU-fibroblast cells) isolated from peripheral blood would have not expressed CD45 since Baksh teaches CD45+ bone marrow cells demonstrate no capacity to form CFU-Fs (p. 3015, right col, para 3 and Fig 3 legend).
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Claim 22 is rejected under 35 U.S.C. 103 as being unpatentable over Yang et al., (Andrology, 2018, 6, 498-509) in view of Ichim et al., (J Transl Med. 2018;16:212, p. 1-9. Cited in IDS 10/12/2022) and Ohara et al., (Gene Therapy. 2001;8: 837-845), as applied to claims 2 and 1 above, and further evidenced by Tito et al., (Mol Biotechnol. 2019;61(3):209-220).
Claim 22 is examined as the regenerative fibroblast cells having GDF-11 expression, as discussed above.
Tito evidences that fibroblasts (e.g., human dermal fibroblasts) have GDF-11 expression (see e.g., p. 213, right col, see Fig 2A and 2B).
Accordingly, one of ordinary skill in the art before the effective filing date of the claimed invention would have immediately expected that the bFGF-secreting fibroblasts of Yang in view of Ichim and Ohara, would have had GDF-11 expression since Tito evidences that fibroblasts (e.g., human dermal fibroblasts) have GDF-11 expression (see e.g., p. 213, right col, see Fig 2A and 2B).
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Claims 43-46 are rejected under 35 U.S.C. 103 as being unpatentable over Yang et al., (Andrology, 2018, 6, 498-509) in view of Ichim et al., (J Transl Med. 2018;16:212, p. 1-9. Cited in IDS 10/12/2022) and Ohara et al., (Gene Therapy. 2001;8: 837-845), as applied to claim 1 above, and further in view of Gou et al., (Asian J Androl. 2011;13(2):332-338).
Claims 43-45 are directed to a committed endothelial progenitor cell (EPC) population being administered in combination with the fibroblast cells. Claim 46 is directed to the committed EPCs expressing CD34, AC133 or flk1.
However, Yang, Ichim and Ohara are silent on a committed EPC population in claims 43-45, nor teach the EPCs express CD34, AC133 or flk1 in claim 46.
Gou teaches a method of treating ED by administering VEGF165-transfected EPCs (equivalent to the claimed committed EPC population in claims 43-45, e.g., abstract, and p. 333, right col, para “EPC transplantation”). Gou teaches administering VEGF165-transfected EPCs significantly increases intracavernosal pressure (e.g., Fig 5) and leads to extensive neovascularisation in the corpora cavernosa (e.g., Figs 7-8). Gou teaches the EPCs express CD34, KDR (a.k.a. flk1) and CD133 (a.k.a. AC133) (p. 334, left col, para “Isolation of EPCs”, and see Fig 2), related to claim 46.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of treating ED by administering bFGF-secreting fibroblasts as suggested by Yang in view of Ichim and Ohara, by combining administering VEGF165-transfected EPCs (i.e., the claimed committed EPC population) expressing CD34, KDR and CD133 as suggested by Gou with a reasonable expectation of success. Since Yang aims to treat ED by cell therapy (see above) and since Gou teaches administering VEGF165-transfected EPCs restores ED by extensive neovascularisation in the corpora cavernosa (e.g., abstract), one of ordinary skill in the art would have had a reason to combine a committed EPC population as suggested by Gou in the method of Yang in view of Ichim and Ohara in order to stimulate extensive neovascularization in the corpora cavernosa to treat ED.
Furthermore, MPEP 2144.06 states "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted). Thus, combining the composition of Gou with the composition of Yang in view of Ichim and Ohara is prima facie obvious.
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Claim 52 is rejected under 35 U.S.C. 103 as being unpatentable over Yang et al., (Andrology, 2018, 6, 498-509) in view of Ichim et al., (J Transl Med. 2018;16:212, p. 1-9. Cited in IDS 10/12/2022), Ohara et al., (Gene Therapy. 2001;8: 837-845) and Gou et al., (Asian J Androl. 2011;13(2):332-338), as applied to claims 45, 44, 43 and 1 above, and further in view of Thom et al., (Am J Physiol Heart Circ Physiol. 2006; 290: H1378-H1386).
Claim 52 is directed to the committed EPCs being isolated from peripheral blood of an individual who has been exposed to therapies of hyperbaric oxygen sufficient to stimulate committed EPCs to enter the peripheral blood, as discussed above.
Gou teaches EPCs are isolated from bone marrows (p. 333, left col, para “Isolation of EPCs”).
However, Yang, Ichim, Ohara and Gou are silent on the endothelial progenitor cells being isolated from peripheral blood following hyperbaric oxygen treatment.
Thom teaches a method of mobilizing bone marrow-derived endothelial progenitor cells from bone marrow to enter peripheral blood by hyperbaric oxygen (see e.g., abstract and Fig 4-5 and Fig 8, and see p. 1385, first full para and Fig 7 for characterizing the mobilized stem/progenitor cells being endothelial progenitor cells).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of treating ED by administering fibroblasts in combination with EPCs isolated from bone marrows as suggested by Yang in view of Ichim, Ohara and Gou, by substituting isolating EPCs from bone marrow with isolating EPCs from peripheral blood following hyperbaric oxygen mobilization as suggested by Thom with a reasonable expectation of success. Since Thom reduces to practice a method of isolating EPCs from peripheral blood following hyperbaric oxygen mobilization (see above), one of ordinary skill in the art would have had a reason to substitute with the method of Thom in order to minimize the invasive procedure to obtain EPCs from peripheral blood for treating ED.
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Double Patenting Rejections
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-2, 4, 63 and 75 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9, 12-15 and 31-32 of US Patent No: 12,310,991 in view of Ryu et al., (Transl Androl Urol. 2012;1(3):173-180). Although the claims at issue are not identical, they are not patentably distinct from each other.
Patent claims recite a method of stimulating angiogenesis in an individual, comprising the step of administering to the individual an effective amount of fibroblast-derived exosomes or one or more biologically active fractions thereof, the method further comprising the steps of obtaining fibroblast cells, culture fibroblast cells in a culture under conditions. The fibroblasts are cultured under hypoxia (patent claim 9), the fibroblasts have been cultured in 2-8% oxygen for at least a day (patent claim 12). It is noted that the instant specification recites that “conditions sufficient to generate regenerative fibroblasts include culture in hypoxic conditions” ([0050]) and “hypoxia is achieved by culture of cells in conditions of 0.1% oxygen to 10% oxygen… for a variety of time points ranging from 1-72 hours” ([0057]). Thus, it is clear that the fibroblasts in the cited patent are regenerative fibroblasts as in the instant invention.
However, cited claims are silent on treating erectile dysfunction (ED), nor teach administering fibroblast cells.
Ryu summarizes methods of treating erectile dysfunction (ED) by therapeutic angiogenesis (e.g., p. 173, right col, also see Fig 1). Ryu teaches ED is predominantly a vascular disease and neovascularization is an emerging therapy for the treatment of ED (e.g., p. 173, right col.), thus suggests that a method of stimulating angiogenesis (as recited in the patent) would be capable of treating ED. Furthermore, Ryu teaches cell therapy is used in treating ED (e.g., Fig 1, right panel), partially through secreting angiogenic factors (p. 175, right col, para 2).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of stimulating angiogenesis recited in the patent, by choosing to use the method in treating ED as suggested by Ryu with a reasonable expectation of success. Since Ryu teaches ED is predominantly a vascular disease and neovascularization is an emerging therapy for the treatment of ED (e.g., p. 173, right col.), one of ordinary skill in the art would have had a reason to use the cited method of stimulating angiogenesis in treating ED as suggested by Ryu in order to apply the cited method to a patient population who suffer from ED and are in need of a neovascularization (i.e., angiogenesis) therapy.
Furthermore, since the patent has recited regenerative fibroblasts (see above) as in the instant invention, and since Ryu teaches cell therapy is used in treating ED (e.g., Fig 1, right panel), partially through secreting angiogenic factors (p. 175, right col, para 2), one of ordinary skill in the art would have substituted regenerative fibroblasts or regenerative fibroblast-conditioned media for the exosomes as suggested by Ryu with a reasonable expectation of success. One of ordinary skill in the art would have had a reason to do so in order to take advantage of the cell therapy and the angiogenic factors secreted by the regenerative fibroblasts.
Since the instant application claims are obvious over cited patent claims, in view of Ryu, said claims are not patentably distinct.
Provisional Double Patenting Rejections
Claims 1-2, 4, 63 and 75 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over copending claims 1-3, 6-8, 12-13 and 31-32 of copending Application No: 18/615,328 in view of Ryu et al., (Transl Androl Urol. 2012;1(3):173-180). Although the claims at issue are not identical, they are not patentably distinct from each other.
Copending claims recite a method of stimulating angiogenesis in an individual, comprising the step of administering to the individual an effective amount of fibroblast-derived exosomes or one or more biologically active fractions thereof, wherein the fibroblasts are cultured under hypoxia (copending claim 1), the method further comprising the steps of obtaining fibroblast cells, culture fibroblast cells in a culture under conditions. The fibroblasts have been cultured in 2-8% oxygen for at least a day (copending claim 12). It is noted that the instant specification recites that “conditions sufficient to generate regenerative fibroblasts include culture in hypoxic conditions” ([0050]) and “hypoxia is achieved by culture of cells in conditions of 0.1% oxygen to 10% oxygen… for a variety of time points ranging from 1-72 hours” ([0057]). Thus, it is clear that the fibroblasts in the cited application are regenerative fibroblasts as in the instant invention.
However, copending claims are silent on treating erectile dysfunction (ED), nor teach administering fibroblast cells.
Ryu summarizes methods of treating erectile dysfunction (ED) by therapeutic angiogenesis (e.g., p. 173, right col, also see Fig 1). Ryu teaches ED is predominantly a vascular disease and neovascularization is an emerging therapy for the treatment of ED (e.g., p. 173, right col.), thus suggests that a method of stimulating angiogenesis (as recited in the application) would be capable of treating ED. Furthermore, Ryu teaches cell therapy is used in treating ED (e.g., Fig 1, right panel), partially through secreting angiogenic factors (p. 175, right col, para 2).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of stimulating angiogenesis recited in the application, by choosing to use the method in treating ED as suggested by Ryu with a reasonable expectation of success. Since Ryu teaches ED is predominantly a vascular disease and neovascularization is an emerging therapy for the treatment of ED (e.g., p. 173, right col.), one of ordinary skill in the art would have had a reason to use the method of stimulating angiogenesis in the copending application in treating ED as suggested by Ryu in order to apply the cited method to a patient population who suffer from ED and are in need of a neovascularization (i.e., angiogenesis) therapy.
Furthermore, since the application has recited regenerative fibroblasts (see above) as in the instant invention, and since Ryu teaches cell therapy is used in treating ED (e.g., Fig 1, right panel), partially through secreting angiogenic factors (p. 175, right col, para 2), one of ordinary skill in the art would have substituted regenerative fibroblasts or regenerative fibroblast-conditioned media for the exosomes as suggested by Ryu with a reasonable expectation of success. One of ordinary skill in the art would have had a reason to do so in order to take advantage of the cell therapy and the angiogenic factors secreted by the regenerative fibroblasts.
Since the instant application claims are obvious over cited application claims, in view of Ryu, said claims are not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims in the copending application have not in fact been patented.
Claims 1-2, 4, 20-22, 63 and 75 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over copending claims 74-75, 94-97, 99 and 101-103 of copending Application No: 17/310,007 in view of Ryu et al., (Transl Androl Urol. 2012;1(3):173-180). Although the claims at issue are not identical, they are not patentably distinct from each other.
Copending claims recite a composition comprising an isolated fibroblast cell, a population thereof, or a conditioned medium thereof wherein the fibroblast cell has an increased regenerative activity compared to a control fibroblast cell, wherein the isolated regenerative cell or population thereof express CD105 marker and/or CD117 marker (reference claim 74, related to instant claims 1, 2, 20 and 75), the fibroblast cell further express marker selected from a group such as Oct-4, and further has enhanced expression of GDF-11 (reference claim 75, related to instant claims 20 and 22), an in vitro isolated fibroblast regenerative cell or population thereof expresses CD105 marker and does not express at least one of MHC class I (reference claim 102, related to instant claim 21), the regenerative activity is the ability to stimulate angiogenesis, wherein said angiogenesis comprises the production of collateral blood vessels (reference claims 94 and 96, related to instant claims 1 and 4), and a pharmaceutical formulation comprising the composition (reference claim 101).
However, copending claims are silent on administering the fibroblast cells or conditioned medium to treat erectile dysfunction (ED).
Ryu summarizes methods of treating erectile dysfunction (ED) by therapeutic angiogenesis (e.g., p. 173, right col, also see Fig 1). Ryu teaches ED is predominantly a vascular disease and neovascularization is an emerging therapy for the treatment of ED (e.g., p. 173, right col.). Ryu teaches cell therapy is used in treating ED (e.g., Fig 1, right panel), partially through secreting angiogenic factors (p. 175, right col, para 2). Thus, Ryu suggests that the fibroblast cells or conditioned medium that can stimulate angiogenesis and production of collateral blood vessels in the copending application is suitable for being administered to treat ED.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the regenerative fibroblast cells or conditioned medium recited in the application, by administering them to treat ED as suggested by Ryu with a reasonable expectation of success. Since Ryu teaches ED is predominantly a vascular disease and neovascularization is an emerging therapy for the treatment of ED (e.g., p. 173, right col.), and cell therapy is used in treating ED (e.g., Fig 1, right panel), partially through secreting angiogenic factors (p. 175, right col, para 2), one of ordinary skill in the art would have had a reason to use the composition in the copending application to treat ED as suggested by Ryu in order to apply the cited composition to a patient population who suffer from ED and are in need of a neovascularization (i.e., angiogenesis) therapy.
Since the instant application claims are obvious over cited application claims, in view of Ryu, said claims are not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims in the copending application have not in fact been patented.
Conclusion
No claims are allowed.
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/JIANJIAN ZHU/Examiner, Art Unit 1631
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