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 .
Claim Rejections - 35 USC § 102
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 (i.e., changing from AIA to pre-AIA ) 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 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.
Claim(s) 1-5, 8-9, 20, and 23-26 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Imbrie et al. (WO 2013/048734).
Regarding claim 1, Imbrie et al. discloses a stent device (Page 8 lines 23-28 disclose a stent device. Page 13 lines 10-20) comprising a plurality of extracellular vesicles (“vesicles” or “exosomes”, page 4 lines 1-26 and pages 32 line 15-page 35 lines 20) conjugated to its surface with a chemical linker (Page 14 line 30-page 15 line 5 discloses the process of linking the vesicles or exosomes to the medical device/stent, which is understood as comprising a chemical linker) .
Regarding claim 2, Imbrie et al. discloses the plurality of extracellular vesicles comprise naturally-occurring and/or engineered exosomes, microvesicles, and/or liposomes (Page 32 discusses naturally occurring exosomes. Liposomes vesicles are also contemplated on pages 34).
Regarding claim 3-4, Imbrie et al. discloses the plurality of extracellular vesicles are derived from adult stem cells, induced pluripotent stem cells, and/or embryonic stem cells, wherein the plurality of extracellular vesicles are derived from mesenchymal stem cells (MSCs), cardiac stem cells (CSCs), cardiac progenitor cells (CPCs), cardiosphere-derived cells (CDCs), hematopoietic stem cells (HSCs), and/or hematopoietic progenitor cells (HPCs) (Page 36 lines 7-13 discloses the use of hematopoietic stem cells, their precursors, or progenitors. Such cell types are of special interest in the treatment of heart disease because bone marrow has been shown to contain cell types capable of regenerating cardiac myocytes when injected into infarcted myocardium).
Regarding claim 5, Imbrie et al. discloses the plurality of extracellular vesicles comprise one or more therapeutic microRNAs (miRNAs) selected from the group consisting of hsa-let-7c-5p, hsa-let-7b-5p, hsa-let-7a-5p, hsa-miR-100-5p, hsa-miR-99a-5p, hsa-let-7f-5p, hsa-miR-23b-3p, hsa-miR-23a-3p, hsa-let-7i-5p, hsa-let-7g- 5p, hsa-miR-10a-5p, hsa-miR-99b-5p, hsa-miR-148a-3p, hsa-miR-191-5p, hsa-miR-26a-5p, hsa-miR-1290, hsa-miR-320a-3p, hsa-miR-320b, hsa-miR-143-3p, hsa-miR-152-3p, hsa- miR-125b-5p, hsa-let-7d-5p, hsa-miR-320c, hsa-miR-3184-3p, hsa-miR-423-5p, and any combinations thereof (Page 41-44 contemplates the use of therapeutic miRNAs).
Regarding claims 8-9, Imbrie et al. discloses the plurality of extracellular vesicles comprise a therapeutic agent, wherein the therapeutic agent comprises an anti- platelet drug and/or a regenerative factor (Page 56 discloses therapeutic agents to be delivered in the vesicales can include anti-platelet drugs, lines 24-25 of page 56).
Regarding claim 20, Imbrie et al. discloses the surface of the device is functionalized (Page 33 line 15-page 34 line 11 discusses functionalization of the surface to target specific cells).
Regarding claim 23, Imbrie et al. discloses A method of treating stenosis, restenosis, and/or ischemic injury comprising implanting the stent of claim 1 into a blood vessel of a subject (“A delivery device coated with vesicles of the invention provides for delivery of the therapeutic nucleic acid or protein contained within the vesicle directly to a blood vessel, including an artery, vein or capillary, directly to an organ (for example the heart), tissue or a specific region of a tissue, or to a cell. For example, organs that may be targeted include the heart, arteries, arterioles, aorta, veins, venules, and capillaries. Similarly, cells that may be targeted include smooth muscle cells, endothelial cells, myocytes, fibroblasts, and macrophages” page 13 lines 10-20. Page 66 lines 19-29 discloses treating stenosis).
Regarding claim 24, Imbrie et al. discloses the ischemic injury comprises myocardial infarction, peripheral artery disease, stroke, mesenteric ischemia and/or renal ischemia (myocardial infarction is a known type of cardiovascular disease/CVD, which is a target of the method, page 25).
Regarding claim 25, Imbrie et al. discloses the stent treats the stenosis or restenosis by increasing endothelial cell proliferation and/or inhibiting smooth muscle cell migration (Page 26 lines 16-22 discloses suppressing smooth muscle cell growth).
Regarding claim 26, Imbrie et al. discloses the stent treats the ischemia by increasing tissue regeneration (Page 36 lines 7-13 discloses the use of hematopoietic stem cells, their precursors, or progenitors. Such cell types are of special interest in the treatment of heart disease because bone marrow has been shown to contain cell types capable of regenerating cardiac myocytes when injected into infarcted myocardium).
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 (i.e., changing from AIA to pre-AIA ) 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.
Claim(s) 6-7 are rejected under 35 U.S.C. 103 as being unpatentable over Imbrie et al. (WO 2013/048734) in view of Zoldan et al. (US 2014/0105960).
Regarding claims 6-7, Imbrie et al. discloses the invention substantially as claimed, as set forth above for claim 2.
Imbrie is silent regarding the liposomes comprise saturated and unsaturated fatty acid chains suitable for lipid particles wherein the fatty acid chains are selected from the group consisting of: 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine (DSPE); 1,2-Distearoyl-sn-glycero-3-phosphocholine (DSPC); 1-palmitoyl-2-oleoyl-sn-glycero-3- phosphocholine (POPC); N-(2,3-dioleoyloxy) propyl)-N,N,N-triethylammonium chloride (DOTAP); and 3-(N-(N', N'-dimethylaminoethane)-carbamoyl) cholesterol (DC-Chol).
However, Zoldan et al. teaches a liposome (FIG 2, [0012]) for delivery of a therapeutic agent (growth factors, [0012 and 0016]), wherein the liposomes comprise a fatty acid chain of DSPC ([0005, 0012-0013, 0016]) which is known to be a low release rate encapsulation ([0005-0006]).
Therefore, it would have bene obvious to one of ordinary skill in the art at the time of filing to select DSPC as a fatty acid chain to form the liposome of Imbrie, for the purpose of creating a particle having the desired drug release properties such as the low release rate of DSPC liposomes (Zoldan [0005]).
Claim(s) 11 is rejected under 35 U.S.C. 103 as being unpatentable over Imbrie et al. (WO 2013/048734).
Regarding claim 11, Imbrie et al. discloses the invention substantially as claimed, as set forth above for claim 1. Imbrie et al. further discloses the size of the vesicles to be about 30-500nm in diameter (page 5 lines 31-32) but fails to disclose the density of which the vesicles are provided on the stent device and therefore fails to specifically disclose the device comprises about 105 to about 1010 extracellular vesicles per mm2.
However, the vesicles of the disclosed size would cover a surface at a rate of 106/mm2 for 500nm diameter to 109/mm2 for 30nm in diameter if supplied on the surface in contact with one another. Thus it is illustrated that the number of vesicles per mm2 is a result effective variable of how densely the particles are arranged on to the surface of the stent. It would have been obvious to one of ordinary skill in the art at the time of filing to select a density of about 105 to about 1010 extracellular vesicles per mm2 as a matter of routine optimization since it has been held that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Claim(s) 13-14 are rejected under 35 U.S.C. 103 as being unpatentable over Imbrie et al. (WO 2013/048734) in view of Milbocker et al. (WO 2012/177825).
Regarding claims 13-14, Imbrie et al. discloses the invention substantially as claimed, as set forth above for claim 1.
Imbrie is silent regarding a portion of the linker is sensitive to a cleavage agent, wherein the cleavage agent is capable releasing the plurality of extracellular vesicles from the device
wherein the linker comprises a reactive oxygen species (ROS)-sensitive portion, and wherein the cleavage agent is an ROS.
However, Milbocker discloses a chemical linker between two compounds delivered to the body (Page 14 paragraph 4) wherein the linker is cleavable and is enzymatically cleavable by reactive oxygen species. Milbocker further discloses that reactive oxygen species are typically associated with inflammation and the chosen link such as urethane is susceptible in this environment.
Therefore, it would have been obvious to one of ordinary skill in the art a the time of filing to modify the chemical linker of Imbrie to be one which is sensitive to a cleavage agent such as an ROS, as taught by Milbocker, for the purpose of selecting a linker which can be cleaved to release the vesicle under the desired, particularly since Milbocker reaches ROS are present in an inflammation environment. Therefore, the vesicles would be configured to deliver the therapeutic agent to a target area of inflammation.
Claim(s) 15-17 are rejected under 35 U.S.C. 103 as being unpatentable over Imbrie et al. (WO 2013/048734) in view of Iyer et al. (WO 2019/133916).
Regarding claims 15-17, Imbrie et al. discloses the invention substantially as claimed, as set forth above for claim 1.
Imbrie is silent regarding the linker comprises a phospholipid-polymer conjugate, wherein the plurality of extracellular vesicles are conjugated to the device via the phospholipid-polymer conjugate,
wherein the phospholipid-polymer conjugate is inserted into the lipid membranes of the plurality of extracellular vesicles, and wherein the phospholipid-polymer conjugate comprises 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-Poly(ethylene glycol) (DSPE- PEG) or any related phosphatidylcholine.
However, Iyer teaches a liposome conjugated to drug delivery system wherein the phospholipid-polymer conjugate DSPE-PEG is used to link the liposome ([0035]).
Therefore, it would have been obvious to one of ordinary skill in the art at the time of filing to select DSPE-PEG as the chemical linker between the vesicle and the delivery device, as taught by Iyer, for the purpose of selecting a phospholipid-polymer conjugate commonly known in the art for creating a cleavable connection for a liposome to achieved a targeted delivery.
Conclusion
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/BROOKE LABRANCHE/Primary Examiner, Art Unit 3771