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 .
Applicant's election without traverse of Group I, claims 1-6 in the reply filed on 9 March 2026 is acknowledged. Non-elected claims 7-11 have been cancelled. Claims 12-20 drawn to elected Group I are newly presented. Claims 1-6 and 12-20 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.
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 2, 5, 6, 15, and 16 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 2 recites “wherein the vascular endothelial progenitor cells and the mesenchymal stem cells are human bone marrow-mesenchymal stem cells.” This claim is indefinite, because it is unclear how the vascular endothelial progenitor cells and the mesenchymal stem cells are both human bone marrow-mesenchymal stem cells (i.e. are both the exact same cell type while also being different cell types).
Claim 5 recites that “the vascular endothelial progenitor cells are located in vascular cells when administered to the subject.” This claim is indefinite, because as currently written, it is unclear if this limitation intends to convey that the vascular endothelial progenitor cells locate to vascular cells within the subject, or instead, that the vascular endothelial progenitor cells are implanted within vascular cells that are then administered to the subject. For the purposes of examination, this claim is interpreted to indicate that the vascular endothelial progenitor cells locate to vascular cells within the subject.
Similarly, claim 6 recites that “the mesenchymal stem cells are located in pericytes when administered to the subject.” This claim is indefinite, because as currently written, it is unclear if this limitation intends to convey that the mesenchymal stem cells locate to pericytes within the subject, or instead, that the mesenchymal stem cells are implanted within pericytes that are then administered to the subject. For the purposes of examination, this claim is interpreted to indicate that the mesenchymal stem cells locate to pericytes within the subject.
Claims 15 and 16 recite that “the composition is administered to a subject having hindlimb ischemia.” These claims depend from claims that indicate that the occlusive vascular disease is peripheral artery disease (PAD) (claim 12), or critical limb ischemia (CLI) (claim 13). It is noted that “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 and CLI, which is a severe form of PAD (see for example Art of Record: Nilyama et al.; Krishna et al.). These claims are indefinite, because it is unclear if/how a subject having PAD or CLI is intended to further have a clinically induced animal model of these diseases.
Claims 15 and 16 are further indefinite for recitation that the composition is administered to “a subject” having hindlimb ischemia. Claim 1, from which these claims depend, recites that the composition is administered to “a subject in need thereof.” As such, it is unclear if reference to “a subject” in claims 15 and 16 is intended to refer to the same subject administered the composition in claim 1, or instead to another subject.
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 12-19 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).
With regard to claim 1, 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).
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 such, the results that the VEPCs are located in vascular cells and the MSCs are located in pericytes when administered to the subject, naturally flow from performance of the taught method.
With regard to claims 12-16, Katritsis et al. teach the administration of a composition comprising mesenchymal stem cells 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 claims 17-19, Katritsis et al. teach the method as claimed, including the steps and components as claimed. As such, the results that the administration increases blood perfusion in an ischemic tissue of the subject; promotes angiogenesis and/or vasculogenesis in the ischemic tissue; and improves limb salvage in the subject, naturally 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.
Conclusion
No claims are allowable.
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).
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/JENNIFER M.H. TICHY/Primary Examiner, Art Unit 1653
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