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 .
Election/Restrictions
Applicant’s election of claims 41-51, and 54-85 in the reply filed on 8 September 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 § 818.01(a)).
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Specification
The abstract of the disclosure is objected to because:
-The abstract contains references to drawing elements in parenthesis. Examiner recommends amending to delete these.
A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Objections
Claims 50, 51, and 54-56 are objected to because of the following informalities:
-Claim 50 recites “from implanting” in line 3. Examiner recommends amending to –from the implanting—to stay consistent with claim language.
-Claims 50, 51, 54, 55, 56, recites “the seeds”. Examiner recommends amending to –the plurality of seeds—
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 75, and 86 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 75 recites “(HGF)/c-MET inhibitor” in line 3. It is unclear whether one or both of (HGF) and c-MET inhibitors are required. Further clarification should be provided.
-Claim 86 recites “at least once…a period between…two weeks before…and six weeks after…seed.” It is unclear whether this limitation refers to a second administration instance, whether the one administration instance is between two weeks before and six weeks after, or a separate embodiment. Further clarification should be provided.
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) 41-48, 57-64, 68-73, 75-77, 80, 83, 86 is/are rejected under 35 U.S.C. 103 as being unpatentable over Keisari (U.S. 20100015042) in view of Baker (U.S. 11389536).
Regarding Claim 41, Keisari teaches a method of treating a patient with a tumor [Abstract], comprising: treating the tumor with intra-tumoral alpha-emitter radiotherapy [0166], [0174], [0176], by implanting a radiotherapy seed in the tumor [0146]—discusses implantation of 224Ra, and further discussion of implanting the radium to expose alpha particles to the tumor cells in [0147-0148]; Keisari is silent on and administering, to the patient, a vascular inhibitor. Baker teaches and administering, to the patient, a vascular inhibitor [Col 20, lines 8-10]. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include a vascular inhibitor as taught by Baker to treat a tumor as suggested by Keisari because Keisari discusses the use of growth factor inhibitors [0080] with Baker because Baker teaches that drugs that interrupt the tumor angiogenesis process show promise in treating cancer [Col 19, lines 34-40].
Regarding Claim 42, Keisari is silent on wherein administering the vascular inhibitor comprises administering a vascular endothelial growth factor (VEGF) blockade. Baker teaches wherein administering the vascular inhibitor comprises administering a vascular endothelial growth factor (VEGF) blockade [Col 20, lines 8-10]—where the process of VEGF blockade is described including use of a VEGF inhibitor to interrupt tumor angiogenesis. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include a vascular inhibitor as taught by Baker to treat a tumor as suggested by Keisari because Keisari discusses the use of growth factor inhibitors [0080] with Baker because Baker teaches that drugs that interrupt the tumor angiogenesis process show promise in treating cancer [Col 19, lines 34-40].
Regarding Claim 43, Keisari further teaches wherein treating the tumor with intra-tumoral alpha-emitter radiotherapy comprises treating a colorectal cancer tumor [0052]—reference to colorectal cancer.
Regarding Claim 44, Keisari is silent on wherein administering the vascular inhibitor comprises administering Bevacizumab. Baker teaches wherein administering the vascular inhibitor comprises administering Bevacizumab [Cols 19-20, lines 65-7]. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use Bevacizumad as taught by Baker to treat a tumor as suggested by Keisari because Keisari discusses the use of growth factor inhibitors [0080] with Baker because Baker teaches direct binding of Bevacizumab to VEGF [Cols 19-20, lines 65-7].
Regarding Claim 45, Keisari is silent on wherein administering the vascular inhibitor comprises administering Ranibizumab. Baker teaches exemplary substances used in this method wherein the substance is Bevacizumab [Cols 19-20, lines 65-7]. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the invention of Keisari and Baker to use Ranibizumab instead of Bevacizumab as these are both known substances that directly bind to VEGF [Cols 19-20, lines 65-7]
Regarding Claim 46, Keisari is silent on wherein administering the vascular inhibitor comprises administering an antiangiogenic agent. Baker teaches wherein administering the vascular inhibitor comprises administering an antiangiogenic agent [Col 20, lines 8-24]. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include a vascular inhibitor as taught by Baker to treat a tumor as suggested by Keisari because Keisari discusses the use of growth factor inhibitors [0080] with Baker because Baker teaches that drugs that interrupt the tumor angiogenesis process show promise in treating cancer [Col 19, lines 34-40].
Regarding Claim 47, Keisari is silent on wherein administering the vascular inhibitor comprises administering a vascular endothelial growth factor (VEGF) inhibitor. Baker teaches wherein administering the vascular inhibitor comprises administering a vascular endothelial growth factor (VEGF) inhibitor [Col 19, lines 32-59]. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include a vascular inhibitor as taught by Baker to treat a tumor as suggested by Keisari because Keisari discusses the use of growth factor inhibitors [0080] with Baker because Baker teaches that drugs that interrupt the tumor angiogenesis process show promise in treating cancer [Col 19, lines 34-40].
Regarding Claim 48, Keisari is silent on wherein administering the vascular inhibitor comprises administering a vascular disrupting agent. Baker teaches wherein administering the vascular inhibitor comprises administering a vascular disrupting agent [Col 20, lines 8-36]. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include a vascular inhibitor as taught by Baker to treat a tumor as suggested by Keisari because Keisari discusses the use of growth factor inhibitors [0080] with Baker because Baker teaches that drugs that interrupt the tumor angiogenesis process show promise in treating cancer [Col 19, lines 34-40].
Regarding Claim 57, Keisari is silent on wherein administering the vascular inhibitor comprises administering an antibody against vascular endothelial growth factors (VEGFs). Baker teaches wherein administering the vascular inhibitor comprises administering an antibody against vascular endothelial growth factors (VEGFs) [Col 24, lines 1-3], [Col 23, lines 37-40] and [Col 23, lines 49-53]. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include antibodies as taught by Baker to treat a tumor as suggested by Keisari because Keisari discusses use of combinations of alpha particles and pharmaceuticals to treat cancer [0147] with Baker because Baker teaches that these antibodies contribute to regulating pathways [Col 23, lines 49-53].
Regarding Claim 58, Keisari is silent on wherein administering the vascular inhibitor comprises administering a vascular endothelial growth factor (VEGF) decoy receptor. Baker teaches wherein administering the vascular inhibitor comprises administering a vascular endothelial growth factor (VEGF) decoy receptor [Col 4, lines 39-57]. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include decoy receptors as taught by Baker to treat a tumor as suggested by Keisari because Keisari discusses use of combinations of alpha particles and pharmaceuticals to treat cancer [0147] with Baker because Baker teaches that these agents increasing activity or effectiveness of chemotherapeutic agents contribute to regulating pathways [Col 4, lines 57-61].
Regarding Claim 59, Keisari is silent on wherein administering the VEGF decoy receptor comprises administering Ziv-aflibercept. Baker teaches wherein administering the VEGF decoy receptor comprises administering Ziv-aflibercept [Col 4, lines 39-57]. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include decoy receptors as taught by Baker to treat a tumor as suggested by Keisari because Keisari discusses use of combinations of alpha particles and pharmaceuticals to treat cancer [0147] with Baker because Baker teaches that these agents increasing activity or effectiveness of chemotherapeutic agents contribute to regulating pathways [Col 4, lines 57-61].
Regarding Claim 60, Keisari is silent on wherein administering the vascular inhibitor comprises administering an antibody against VEGF receptors. Baker teaches wherein administering the vascular inhibitor comprises administering an antibody against VEGF receptors [Col 24, lines 1-3], [Col 23, lines 37-40] and [Col 23, lines 49-53]. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include antibodies as taught by Baker to treat a tumor as suggested by Keisari because Keisari discusses use of combinations of alpha particles and pharmaceuticals to treat cancer [0147] with Baker because Baker teaches that these antibodies contribute to regulating pathways [Col 23, lines 49-53].
Regarding Claim 61, Keisari is silent on wherein administering the vascular inhibitor comprises administering a kinase inhibitor. Baker teaches wherein administering the vascular inhibitor comprises administering a kinase inhibitor [Col 17, lines 44-50]. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include a kinase inhibitor as taught by Baker to treat a tumor as suggested by Keisari because Keisari discusses use of combinations of alpha particles and pharmaceuticals to treat cancer [0147] with Baker because Baker teaches that these inhibitors prevent cellular changes such as division [Col 17, lines 46-50].
Regarding Claim 62, Keisari is silent on wherein administering the kinase inhibitor comprises administering at least one of Sorafenib, Sunitinib, Regorafenib, and Lenvatinib. Baker teaches wherein administering the kinase inhibitor comprises administering at least one of Sorafenib [Col 17, lines 64-67], Sunitinib [Col 19, lines 3-5], Regorafenib [Col 19, lines 60-61], and Lenvatinib [Col 15, lines 54-55]. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include a kinase inhibitor as taught by Baker to treat a tumor as suggested by Keisari because Keisari discusses use of combinations of alpha particles and pharmaceuticals to treat cancer [0147] with Baker because Baker teaches that these inhibitors prevent cellular changes such as division [Col 17, lines 46-50].
Regarding Claim 63, Keisari is silent on wherein administering the vascular inhibitor comprises administering an immunomodulatory imide drug (IMiD). Baker teaches wherein administering the vascular inhibitor comprises administering an immunomodulatory imide drug (IMiD) [Col 20, lines 8-18]. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include a IMiD as taught by Baker to treat a tumor as suggested by Keisari because Keisari discusses use of combinations of alpha particles and pharmaceuticals to treat cancer [0147] with Baker because Baker teaches these agents to activate the immune system [Col 20, lines 8-18].
Regarding Claim 64, Keisari is silent on wherein administering the IMiD comprises administering at least one of Thalidomide, Pomalidomide, and Lenalidomide. Baker teaches wherein administering the IMiD comprises administering at least one of Thalidomide [Col 20, lines 14-15], Pomalidomide, and Lenalidomide [Col 22, lines 52-53]. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include a IMiD as taught by Baker to treat a tumor as suggested by Keisari because Keisari discusses use of combinations of alpha particles and pharmaceuticals to treat cancer [0147] with Baker because Baker teaches these agents to activate the immune system [Col 20, lines 8-18].
Regarding Claim 68, Keisari is silent on wherein administering the vascular inhibitor comprises administering an mTOR inhibitor. Baker teaches wherein administering the vascular inhibitor comprises administering an mTOR inhibitor [Col 17, lines 6-7]. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include a mTOR inhibitor as taught by Baker to treat a tumor as suggested by Keisari because Keisari discusses use of combinations of alpha particles and pharmaceuticals to treat cancer [0147] with Baker because Baker teaches these agents to inhibit protein synthesis [Col 16, lines 35-39].
Regarding Claim 69, Keisari is silent on wherein administering the vascular inhibitor comprises administering rapamycin. Baker teaches wherein administering the vascular inhibitor comprises administering rapamycin [Col 16, lines 46-47]. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include a mTOR inhibitor as taught by Baker to treat a tumor as suggested by Keisari because Keisari discusses use of combinations of alpha particles and pharmaceuticals to treat cancer [0147] with Baker because Baker teaches these agents to inhibit protein synthesis [Col 16, lines 35-39].
Regarding Claim 70, Keisari is silent on wherein administering the vascular inhibitor comprises administering a Fibroblast Growth Factor inhibitor. Baker teaches wherein administering the vascular inhibitor comprises administering a Fibroblast Growth Factor inhibitor [Col 18, lines 32-36]. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include a FGFR inhibitor as taught by Baker to treat a tumor as suggested by Keisari because Keisari discusses use of combinations of alpha particles and pharmaceuticals to treat cancer [0147] with Baker because Baker teaches these agents to inhibit FGF signal transduction, proliferation and differentiation of wide variety of tissue [Col 18, lines 34-41].
Regarding Claim 71, Keisari is silent on wherein administering the vascular inhibitor comprises administering Brivanib. Baker teaches wherein administering the vascular inhibitor comprises administering Brivanib [Col 15, lines 54-55]. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use Brivanib as taught by Baker to treat a tumor as suggested by Keisari because Keisari discusses use of combinations of alpha particles and pharmaceuticals to treat cancer [0147] with Baker because Baker teaches these agents are typically used in cancer patients [Col 15, lines 44-45].
Regarding Claim 72, Keisari is silent on wherein administering the vascular inhibitor comprises administering an Angiopoietin inhibitor. Baker teaches wherein administering the vascular inhibitor comprises administering an Angiopoietin inhibitor [Col 23, lines 62-66]. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use angiopoietin inhibitors as taught by Baker to treat a tumor as suggested by Keisari because Keisari discusses use of combinations of alpha particles and pharmaceuticals to treat cancer [0147] with Baker because Baker teaches the effects of these agents on angiogenesis and metastasis [Col 23, lines 58-66].
Regarding Claim 73, Keisari is silent on wherein administering the vascular inhibitor comprises administering a Platelet- Derived Growth Factor inhibitor. Baker teaches wherein administering the vascular inhibitor comprises administering a Platelet- Derived Growth Factor inhibitor [Col 26, lines 11-13]. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use PDGFR as taught by Baker to treat a tumor as suggested by Keisari because Keisari discusses use of combinations of alpha particles and pharmaceuticals to treat cancer [0147] with Baker because Baker teaches the effects of these agents on survival, angiogenesis, proliferation and invasion pathways [Col 26, lines 11-16].
Regarding Claim 75, Keisari is silent on wherein administering the vascular inhibitor comprises administering a Hepatocyte Growth Factor (HGF)/c-MET inhibitor. Baker teaches wherein administering the vascular inhibitor comprises administering a Hepatocyte Growth Factor (HGF)/c-MET inhibitor [Col 16, lines 13-14]. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use PDGFR as taught by Baker to treat a tumor as suggested by Keisari because Keisari discusses use of combinations of alpha particles and pharmaceuticals to treat cancer [0147] with Baker because Baker teaches the effects of these agents on PI3K and RAS signaling [Col 21, lines 29-31].
Regarding Claim 76, Keisari is silent on wherein administering the vascular inhibitor comprises administering a naturally anti-angiogenic factor, or a derivative or a mimic of a naturally anti-angiogenic factor. Baker teaches wherein administering the vascular inhibitor comprises administering a naturally anti-angiogenic factor, or a derivative or a mimic of a naturally anti-angiogenic factor [Col 19, lines 64-66]. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use natural angiogenesis inhibitors as taught by Baker to treat a tumor as suggested by Keisari because Keisari discusses use of combinations of alpha particles and pharmaceuticals to treat cancer [0147] with Baker because Baker teaches direct binding of these agents to VEGF[Col 20, lines 1-2].
Regarding Claim 77, Keisari is silent on wherein administering the vascular inhibitor comprises administering Endostatin. Baker teaches wherein administering the vascular inhibitor comprises administering Endostatin [Col 20, lines 9-16]. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use natural angiogenesis inhibitors as taught by Baker to treat a tumor as suggested by Keisari because Keisari discusses use of combinations of alpha particles and pharmaceuticals to treat cancer [0147] with Baker because Baker teaches direct binding of these agents to VEGF [Col 20, lines 1-2].
Regarding Claim 80, Keisari is silent on wherein administering the vascular inhibitor comprises administering an angiogenesis inhibitor. Baker teaches wherein administering the vascular inhibitor comprises administering an angiogenesis inhibitor [Col 20, lines 8-10]. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use angiogenesis inhibitors as taught by Baker to treat a tumor as suggested by Keisari because Keisari discusses use of combinations of alpha particles and pharmaceuticals to treat cancer [0147] with Baker because Baker teaches direct binding of these agents to VEGF [Col 20, lines 1-2].
Regarding Claim 83, Keisari is silent on wherein administering the vascular inhibitor comprises administering a matrix metalloproteinase inhibitor. Baker teaches wherein administering the vascular inhibitor comprises administering a matrix metalloproteinase inhibitor [Col 20, lines 9-13]. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use matrix metalloproteinase inhibitors as taught by Baker to treat a tumor as suggested by Keisari because Keisari discusses use of combinations of alpha particles and pharmaceuticals to treat cancer [0147] with Baker because Baker teaches these agents causing basement membrane degradation [Col 20, lines 21-24].
Regarding Claim 86, Keisari further teaches at least once during a period between two weeks before implanting the radiotherapy seed and six weeks after implanting the radiotherapy seed [0166], [0174], [0176]—where this time period is interpreted to be provided within the range of two weeks before and six weeks after implanting the radiotherapy seed. Keisari is silent on wherein the vascular inhibitor is administered to the patient. Baker teaches wherein the vascular inhibitor is administered to the patient [Col 20, lines 8-10]. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include a vascular inhibitor as taught by Baker to treat a tumor as suggested by Keisari because Keisari discusses the use of growth factor inhibitors administered every 3 days for 3-10 times [0124] and [0080] with Baker because Baker teaches the importance of fractionation to allow normal cells time to recover [Col 13, lines 20-30].
Claim(s) 74, 66-67, 79, 81 and 84 is/are rejected under 35 U.S.C. 103 as being unpatentable over Keisari (U.S. 20100015042) in view of Baker (U.S. 11389536) and in further view of Bolen (WO 2018102397).
Regarding Claim 74, Keisari and Baker are silent on wherein administering the vascular inhibitor comprises administering ponatinib. Bolen teaches wherein administering the vascular inhibitor comprises administering ponatinib [00871] and [00826]—which discusses targeting/decreasing protein or lipid kinase activity and anti-angiogenic compounds. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use ponatinib as taught by Bolen to treat cancer as suggested by Keisari, and Baker because Keisari discusses use of combinations of alpha particles and pharmaceuticals to treat cancer [0147] and Baker which teaches binding with VEGF [Cols 19-20, lines 65-7] with Bolen because Bolen teaches this compound used as an additional therapeutic agent [00871].
Regarding Claim 66, Keisari and Baker are silent on wherein administering the vascular inhibitor comprises administering an Endothelin receptor blocker. Bolen teaches wherein administering the vascular inhibitor comprises administering an Endothelin receptor blocker [00871] and [00826]—which discusses targeting/decreasing protein or lipid kinase activity and anti-angiogenic compounds. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use an endothelin receptor blocker as taught by Bolen to treat cancer as suggested by Keisari, and Baker because Keisari discusses use of combinations of alpha particles and pharmaceuticals to treat cancer [0147] and Baker which teaches binding with VEGF [Cols 19-20, lines 65-7] with Bolen because Bolen teaches this agent used as an additional therapeutic agent [00871].
Regarding Claim 67, Keisari and Baker are silent on wherein administering the vascular inhibitor comprises administering Bosentan. Bolen teaches wherein administering the vascular inhibitor comprises administering Bosentan [00871] and [00826]—which discusses targeting/decreasing protein or lipid kinase activity and anti-angiogenic compounds. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use Bosentan as taught by Bolen to treat cancer as suggested by Keisari, and Baker because Keisari discusses use of combinations of alpha particles and pharmaceuticals to treat cancer [0147] and Baker which teaches binding with VEGF [Cols 19-20, lines 65-7] with Bolen because Bolen teaches this compound used as an additional therapeutic agent [00871].
Regarding Claim 79, Keisari and Baker are silent on wherein administering the vascular inhibitor comprises administering Propranolol. Bolen teaches wherein administering the vascular inhibitor comprises administering Propranolol [00871] and [00826]—which discusses targeting/decreasing protein or lipid kinase activity and anti-angiogenic compounds. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use Propranolol as taught by Bolen to treat cancer as suggested by Keisari, and Baker because Keisari discusses use of combinations of alpha particles and pharmaceuticals to treat cancer [0147] and Baker which teaches binding with VEGF [Cols 19-20, lines 65-7] with Bolen because Bolen teaches this compound used as an additional therapeutic agent [00871].
Regarding Claim 81, Keisari and Baker are silent on wherein administering the vascular inhibitor comprises administering Metformin or Chloroquine. Bolen teaches wherein administering the vascular inhibitor comprises administering Metformin [Pg. 136, “examples of clinical use” column] or Chloroquine [00805] and [00826]—which discusses targeting/decreasing protein or lipid kinase activity and anti-angiogenic compounds. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use Metformin or Chloroquine as taught by Bolen to treat cancer as suggested by Keisari, and Baker because Keisari discusses use of combinations of alpha particles and pharmaceuticals to treat cancer [0147] and Baker which teaches binding with VEGF [Cols 19-20, lines 65-7] with Bolen because Bolen teaches this compound used as an additional therapeutic agent [00871].
Regarding Claim 84, Keisari and Baker are silent on wherein administering the vascular inhibitor comprises administering an inhibitor of integrin's pro-angiogenic activity. Bolen teaches wherein administering the vascular inhibitor comprises administering an inhibitor of integrin's pro-angiogenic activity [00418]. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use integrin’s pro-angiogenic activity as taught by Bolen to treat cancer as suggested by Keisari, and Baker because Keisari discusses use of combinations of alpha particles and pharmaceuticals to treat cancer [0147] and Baker which teaches binding with VEGF [Cols 19-20, lines 65-7] with Bolen because Bolen teaches this agent targeting VEGF [00418].
Claim(s) 65, 78 is/are rejected under 35 U.S.C. 103 as being unpatentable over Keisari (U.S. 20100015042) in view of Baker (U.S. 11389536) and in further view of Almstead (CN 102480957).
Regarding Claim 65, Keisari and Baker are silent on wherein administering the vascular inhibitor comprises administering an antiangiogenic microRNA. Almstead teaches wherein administering the vascular inhibitor comprises administering an antiangiogenic microRNA [0453]. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use anti-angiogenic mircoRNA as taught by Almstead to treat cancer as suggested by Keisari, and Baker because Keisari discusses use of combinations of alpha particles and pharmaceuticals to treat cancer [0147] and Baker which teaches binding with VEGF [Cols 19-20, lines 65-7] with Almstead because Almstead teaches the anti-angiogenic agents combined with compounds for treatment of cancer [0453].
Regarding Claim 78, Keisari and Baker are silent on wherein administering the vascular inhibitor comprises administering one or more β-adrenergic drugs. Almstead teaches wherein administering the vascular inhibitor comprises administering one or more β-adrenergic drugs [0403]. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use β-adrenergic drugs as taught by Almstead to treat cancer as suggested by Keisari, and Baker because Keisari discusses use of combinations of alpha particles and pharmaceuticals to treat cancer [0147] and Baker which teaches binding with VEGF [Cols 19-20, lines 65-7] with Almstead because Almstead teaches the β-adrenergic drugs administration timing in respect to cancer treatment [0403].
Claim(s) 49, 50, 51, 54, 55, 56 is/are rejected under 35 U.S.C. 103 as being unpatentable over Keisari (U.S. 20100015042) in view of Baker (U.S. 11389536) and in further view of Hunter (U.S. 20030144570).
Regarding Claim 49, Keisari and Baker are silent on wherein treating the tumor with intra-tumoral alpha-emitter radiotherapy comprises implanting a plurality of seeds each having a length of at least 1 millimeter, in the tumor. Hunter teaches wherein treating the tumor with intra-tumoral alpha-emitter radiotherapy comprises implanting a plurality of seeds each having a length of at least 1 millimeter, in the tumor [0009]. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use a plurality of radioactive seeds at a length of at least 1 millimeter as taught by Hunter to treat a tumor as suggested by Keisari, and Baker, because Keisari discusses tumor size [0041] and Baker which discloses considerations according to size of tumor [Col 26, lines 18-23] with Hunter because Hunter teaches size considerations according to seed loader and implantation device [0331].
Regarding Claim 50, Keisari further teaches comprises administering within less than five days from implanting of the seeds [0166], [0174], [0176]. Keisari is silent on wherein administering the vascular inhibitor. Baker teaches wherein administering the vascular inhibitor [Col 20, lines 8-10]. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include a vascular inhibitor as taught by Baker to treat a tumor as suggested by Keisari because Keisari discusses the use of growth factor inhibitors administered every 3 days for 3-10 times [0124] and [0080] with Baker because Baker teaches the importance of fractionation to allow normal cells time to recover [Col 13, lines 20-30].
Regarding Claim 51, Keisari further teaches comprises administering at least 12 hours after the implanting of the seeds [0148]. Keisari is silent on wherein administering the vascular inhibitor. Baker teaches wherein administering the vascular inhibitor [Col 20, lines 8-10]. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include a vascular inhibitor as taught by Baker to treat a tumor as suggested by Keisari because Keisari discusses the use of growth factor inhibitors administered every 3 days for 3-10 times [0124] and [0080] with Baker because Baker teaches the importance of fractionation to allow normal cells time to recover [Col 13, lines 20-30].
Regarding Claim 54, Keisari further teaches comprises administering at least 72 hours after the implanting of the seeds [0166]—reference to the second administration. Keisari is silent on wherein administering the vascular inhibitor. Baker teaches wherein administering the vascular inhibitor [Col 20, lines 8-10]. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include a vascular inhibitor as taught by Baker to treat a tumor as suggested by Keisari because Keisari discusses the use of growth factor inhibitors administered every 3 days for 3-10 times [0124] and [0080] with Baker because Baker teaches the importance of fractionation to allow normal cells time to recover [Col 13, lines 20-30].
Regarding Claim 55, Keisari further teaches comprises administering at least 12 hours before the implanting of the seeds [0166]—reference to administration one day prior to DART. Keisari is silent on wherein administering the vascular inhibitor. Baker teaches wherein administering the vascular inhibitor [Col 20, lines 8-10]. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include a vascular inhibitor as taught by Baker to treat a tumor as suggested by Keisari because Keisari discusses the use of growth factor inhibitors administered every 3 days for 3-10 times [0124] and [0080] with Baker because Baker teaches the importance of fractionation to allow normal cells time to recover [Col 13, lines 20-30].
Regarding Claim 56, Keisari is silent on wherein administering the vascular inhibitor comprises administering at least 72 hours before the implanting of the seeds. Baker teaches wherein administering the vascular inhibitor comprises administering at least 72 hours before the implanting of the seeds [Col 26, lines 51-56]—reference to 6-12 days before cytotoxic administration. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to administer the vascular inhibitor at least 72 hours before as taught by Baker to treat a tumor as suggested by Keisari because Keisari discusses achieving smaller tumor volumes [0166] with Baker because Baker teaches timing being associated with therapeutic response and sensitization [Col 26, lines 48-59].
Claim(s) 82 and 85 is/are rejected under 35 U.S.C. 103 as being unpatentable over Keisari (U.S. 20100015042) in view of Baker (U.S. 11389536) and in further view of Kasai (WO 2010119992).
Regarding Claim 82, Keisari and Baker are silent on wherein administering the vascular inhibitor comprises administering a Cannabinoid. Kasai teaches wherein administering the vascular inhibitor comprises administering a Cannabinoid [0166] and [Pg. 179]-discussion related to use of the compounds described in the invention for treatment of cancerous cachexia. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use cannabinoids as taught by Kasai to treat cancer as suggested by Keisari, and Baker because Keisari discusses use of combinations of alpha particles and pharmaceuticals to treat cancer [0147] and Baker which teaches binding with VEGF [Cols 19-20, lines 65-7] with Kasai because Kasai teaches the use of antiobestic agents for cancer treatment [0166].
Regarding Claim 85, Keisari and Baker are silent on wherein administering the vascular inhibitor comprises administering Combretastatin A-4 phosphate (CA4P). Kasai teaches wherein administering the vascular inhibitor comprises administering Combretastatin A-4 phosphate (CA4P) [Pg. 188, lines 14-22] and [Pg. 179]-discussion related to use of the compounds described in the invention for treatment of cancerous cachexia. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use CA4Ps as taught by Kasai to treat cancer as suggested by Keisari, and Baker because Keisari discusses use of combinations of alpha particles and pharmaceuticals to treat cancer [0147] and Baker which teaches binding with VEGF [Cols 19-20, lines 65-7] with Kasai because Kasai teaches CA4P as an anti-angiogenic/anti-VEGF drug [Pg. 188].
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
-Sukumar (WO 2017062394)—describes the use of alpha particles and pharmaceutical combination therapy
-Harris (AU 2012271450)—includes reference to enhancing radiotherapy using pharmaceuticals
-West (U.S. 10961531)—discloses references relevant to angiogenic therapies
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/B.N.K./Examiner, Art Unit 3791
/CHRISTINE H MATTHEWS/Primary Examiner, Art Unit 3791
