DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This Office Action is in response to the paper filed 2 July 2026. Claims 1, 2, 5, 6, and 15-20 have been amended. Claims 12-14 have been cancelled. Claims 1-6 and 15-20 are currently pending and under examination.
This Application is a national phase application under 35 U.S.C. §371 of International Application No. PCT/KR2022/005118, filed 8 April 2022, which claims priority to Korean patent document No. KR10-2021-0049817, filed 16 April 2021.
Withdrawal of Rejections:
The previous rejection of claims 2, 5, 6, 15, and 16 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite, is withdrawn.
New Objections/Rejections Necessitated by Amendment:
Claim Objections
Claims 15 and 16 are objected to because of the following informalities: these claims as amended now recite “wherein the the subject…” (emphasis added). The duplicate “the” should be removed. 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.
Claims 1-6 and 15-20 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.
Claim 1 as amended recites “wherein the an occlusive vascular disease” (emphasis added). This limitation is indefinite, because as currently written, it is unclear if the vascular disease recited in this line is intended to refer to the previously recited occlusive vascular disease in the preamble, or instead, to a newly included occlusive vascular disease.
The term “increasing blood perfusion” in claim 17 is a relative term which renders the claim indefinite. The term “increasing” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear what amount of blood perfusion in an ischemic tissue is required to be included in, or excluded from, the limitation as claimed.
Claim 19 is likewise rejected for recitation of “improving limb salvage.”
The term “promoting angiogenesis and/or vasculogenesis” in claim 18 is a relative term which renders the claim indefinite. The term “promoting” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear what amount of promotion of angiogenesis and/or vasculogenesis in the ischemic tissue is required to be included in, or excluded from, the limitation as claimed.
Claims 2-6, 15, 16, and 20 are included in this rejection, as these claims depend from above rejected claims and fails to remedy the noted deficiencies.
Maintenance/Modification of Rejections Necessitated by Amendment:
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-3, 5, 6, and 15-19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Katritsis et al. (Transcoronary Transplantation of Autologous Mesenchymal Stem Cells and Endothelial Progenitors Into Infarcted Human Myocardium, Catheterization and Cardiovascular Interventions, Vol. 65, (2005), pp. 321-329 – Previously Presented).
With regard to claims 1, 15, and 16, Katritsis et al. teach the treatment of anteroseptal myocardial infarction, which is an occlusive vascular disease, the method including administering a composition comprising mesenchymal stem cells (MSCs) and endothelial progenitor cells as the active ingredients to a subject in need thereof (Abs.). As the endothelial progenitor cells present in the method of Katritsis et al. are likewise derived from human bone marrow and utilized for treating an occlusive vascular disease (Abs.; p. 322, Left Col., Materials and Methods, Patients; Bone Marrow Aspiration, Isolation and Culture), the endothelial progenitor cells as taught are vascular endothelial progenitor cells (VEPCs).
It is noted that Applicant does not claim a method for treating an occlusive vascular disease or an ulcer resulting therefrom in a subject in need thereof, where the active ingredients are administered to the subject in need thereof. Instead, as currently claimed, it is only required that administration of the active ingredients be to a subject in need of the active ingredients (e.g. a subject in need of administration of the active ingredients to treat anteroseptal myocardial infarction). As currently written, the intended use as set forth in the preamble and wherein clause would necessarily be provided when the subject in need of the active ingredients is treated using the active ingredients.
Katritsis et al. teach the administration of a composition comprising MSCs and VEPCs as the active ingredients to a subject for treatment of anteroseptal myocardial infarction (Abs.), which is administration of the composition to a subject in need thereof. As such, administration of the composition to the subject as taught by Katritsis et al. would necessarily treat the occlusive vascular disease peripheral artery disease (PAD), including critical limb ischemia (CLI), and its clinical model hindlimb ischemia, and would also necessarily treat an ulcer resulting from an occlusive vascular disease, including an ischemic foot ulcer.
With regard to claim 2, Katritsis et al. teach that the MSCs and VEPCs are derived from human bone marrow (Abs.; p. 322, Left Col., Materials and Methods, Patients; Bone Marrow Aspiration, Isolation and Culture).
With regard to claim 3, Katritsis et al. teach the treatment of anteroseptal myocardial infarction (Abs.), which is an occlusive vascular disease, and is a cardiovascular disease, arteriovascular disease, and a coronary artery disease.
With regard to claims 5 and 6, Katritsis et al. teach the method as claimed, including the steps and components as claimed. As the VEPCs and MSCs cannot be separated from their inherent functions, the results that the VEPCs differentiate into vascular endothelial cells, and the MSCs serve as pericytes, when administered to the subject, would necessarily flow from performance of the taught method.
With regard to claims 17-19, Katritsis et al. teach the method as claimed, including the steps and components as claimed. As the VEPCs and MSCs cannot be separated from their inherent functions, the results that the administration increases blood perfusion in an ischemic tissue; promotes angiogenesis and/or vasculogenesis in ischemic tissue; and improves limb salvage, including in a subject that requires such results, necessarily flow from performance of the taught method.
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.
Claims 1, 4, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Katritsis et al.
The teachings of Katritsis et al. as applied to claim 1 have been set forth above.
With regard to claim 4, Katritsis et al. teach that 1-2 x106 cells are infused into the human patient (p. 322, Right Col., Intracoronary Transplantation, para. 1). It is noted that the average weight of a North American adult human in 2005 was 80.7 kg (see Art of Record: Wikipedia). As such, the composition would have been expected to be administered at a dose of about 9 x105 cell/kg body weight, which is encompassed within 1.2x105 to 1.2x107 cell/kg body weight. Further, it would have been obvious to one of ordinary skill in the art to administer the composition based the individual characteristics of each subject. Additionally, it is noted that "the discovery of an optimum value of a variable in a known process is usually obvious." Pfizer v. Apotex, 480 F.3d at 1368. The rationale for determining the optimal parameters for prior art result effective variables "flows from the 'normal desire of scientists or artisans to improve upon what is already generally known.'" Id. (quoting In re Peterson, 315 F.3d 1325, 1330 (Fed. Cir. 2003)). Accordingly, it would have been obvious to optimize the dosage of the cells administered, including in and amount of 1.2x105 to 1.2x107 cell/kg body weight, to result in the administration of an effective amount of the composition for treating a specific patient based on factors including age, sex, weight, comorbid conditions, and disease severity when practicing the taught method.
With regard to claim 20, Katritsis et al. further teach that the administered cells, which are harvested from the subject and administered after 7 days of culturing, include 28% ± 11% VEPCs and 66% ±19% MSCs (p. 322, Left col. Bone Marrow Aspiration, Isolation, and Culture to Right col., Monoclonal Antibodies and Immunophenotyping; Fig. 1). While it is not specifically taught that the cells are administered in a ratio of VEPCs:MSCs of 2:1, one of ordinary skill in the art would have understood that there is significant variability in the concentration of each cell type following harvesting and pre-transplant culturing. As such, it would have been obvious to one of ordinary skill in the art to determine the most effective ratio of VEPCs:MSCs for administration based on the data obtained from the subjects studied.
Additionally, it is noted that "the discovery of an optimum value of a variable in a known process is usually obvious." Pfizer v. Apotex, 480 F.3d at 1368. The rationale for determining the optimal parameters for prior art result effective variables "flows from the 'normal desire of scientists or artisans to improve upon what is already generally known.'" Id. (quoting In re Peterson, 315 F.3d 1325, 1330 (Fed. Cir. 2003)). Accordingly, it would have been obvious to optimize the amount of the two active ingredients in the combined composition, including in a VEPC:MSC ratio of 2:1, to result in administration of a composition effective for treating a specific patient based on factors including age, sex, weight, comorbid conditions, and disease severity when practicing the taught method.
Response to Arguments
Applicant urges that the claims are directed to a specific patient population as now claimed, and Katritsis does not teach or render obvious treating such a population.
Applicant’s arguments have been fully considered, but have not been found persuasive.
As discussed in the modified rejection above, it is noted that Applicant does not claim a method for treating an occlusive vascular disease or an ulcer resulting therefrom in a subject in need thereof, where the active ingredients are administered to the subject in need thereof. Instead, as currently claimed, it is only required that administration of the active ingredients be to a subject in need of the active ingredients (e.g. a subject in need of administration of the active ingredients to treat anteroseptal myocardial infarction). As currently written, the intended use as set forth in the preamble and wherein clause would necessarily be provided when the subject in need of the active ingredients is treated using the active ingredients.
Katritsis et al. teach the administration of a composition comprising MSCs and VEPCs as the active ingredients to a subject for treatment of anteroseptal myocardial infarction (Abs.), which is administration of the composition to a subject in need thereof. As such, administration of the composition to the subject as taught by Katritsis et al. would necessarily treat the occlusive vascular disease peripheral artery disease (PAD), including critical limb ischemia (CLI), and its clinical model hindlimb ischemia, and would also necessarily treat an ulcer resulting from an occlusive vascular disease, including an ischemic foot ulcer.
Conclusion
No claims are allowable.
Previously Presented Art of Record:
Krishna et al., A Review of the Pathophysiology and Potential Biomarkers for Peripheral Artery Disease, International Journal of Molecular Sciences, Vol. 16, (2015), pp. 11294-11322 (CLI is a severe form of PAD and hindlimb ischemia is an animal model for the study of PAD/CLI).
Nilyama et al., Murine Model of Hindlimb Ischemia, Journal of Visualized Experiments, Vol. 23, (2009), pp. 1-4 (“hindlimb ischemia” is an ischemia model that is clinically induced in animals in a laboratory setting as a model to mimic and study human PAD)
Wikipedia; Human body weight, accessed 3/3/2026, Available online at: en.wikipedia.org/wiki/Human_body_weight (average weight of a North American adult human in 2005 was 80.7 kg).
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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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/JENNIFER M.H. TICHY/Primary Examiner, Art Unit 1653
