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 .
Summary
Claims 1-36 are pending in this office action. All pending claims are under examination in this application.
Priority
The current application was filed on May 9, 2024 is a 371 of PCT/US2022/049793 filed on November 14, 2022, which in turn claims domestic priority to provisional patent application, 63/278,697, filed on November 12, 2021.
Information Disclosure Statement
Receipt of the Information Disclosure Statements filed on May 9, 2024 and December 12, 2025 are acknowledged. A signed copy of both documents are attached to this office action.
Claim Objections
Claims 1-36 are objected to because of the following informalities:
Claims 1, 9, 21, and 31: Please numerically identify the parts of the claims that are separate from the other limitations for ease of reading by a skilled artisan (for example, 1., 2., 3., etc.). As currently constructed the body of the claims have no clear markers/separation other than text.
Dependent claims 2-8, 10-20, 22-30, and 32-36 are included here because they do not cure the defects of their corresponding independent claims.
Claims 5, 7, 15, and 17: Please use lowercase to identify the isotope (for example, iodine-131).
Claim 9: Please indent the body text of the claim which states, “a second radioembolic agent…” in order to consistently indent the claim.
Claims 18 and 30: Please use the full name of the radioelements (for example, iodine-125 instead of I-125) to be consistent with the claim set.
Appropriate correction is required.
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.
Claims 1 and 6-8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Fritz et al. (US2015/0258224A1).
Fritz et al. is considered the closest prior art to the present invention as it teaches loadable polymeric particles for enhanced imaging in clinical applications and methods of preparing and using the same (see title). Furthermore, Fritz et al. disclose that particles are provided for use in therapeutic and/or diagnostic procedures. The particles include poly[bis(trifluoroethoxy)phosphazene] and/or a derivatives thereof which may be present throughout the particles or within an outer coating of the particles. The particles can also include a core having a hydrogel formed from an acrylic-based polymer. Such particles may be provided to a user in specific selected sizes to allow for selective embolization of certain sized blood vessels or localized treatment with an active component agent in specific clinical uses. Microspheres of the present invention may further be provided with physical and/or chemical enhancements within the particles' cores to enhance visualization of the embolized tissue using a variety of medical imaging modalities, including conventional radiography, fluoroscopy, tomography, computerized tomography, ultrasound, scintillation, magnetic resonance, or other imaging technologies (see abstract).
Regarding instant claim 1, Fritz et al. teach a liquid radioembolic agent for delivering local radiation to a target location while also causing devascularization at the target location. The necessary citations within Fritz et al. that pertain to instant claim 1 are presented in Table I.
Table I
Instant Claim 1
Fritz et al. Citations
A liquid radioembolic agent for delivering local radiation to a target location while also causing devascularization at the target location, the liquid radioembolic agent comprising:
Fritz et al. disclose a liquid radioembolic agent for delivering local radiation to a target location while also causing devascularization at the target location (see para [0036], [0090], and [0097]; also see claims 39 and 42, microsphere particles for devascularization of target tissue are placed in a suspension liquid and injected.).
a biocompatible prepolymer;
Fritz et al. disclose the liquid radioembolic agent comprises: a biocompatible prepolymer (see Table 1; and para [0040]-(0042], [0068], and [0072], biocompatible polymers and prepolymers with biological inertness …PMMA monomer);
a first radioisotope having a first type of ionizing radiation for treatment of a first region of the target location;
Fritz et al. disclose a first radioisotope having a first type of ionizing radiation for treatment of a first region of the target location (see para [0036], [0090], [0097], [0116], [0180]-[0183], and [0199]-[0200]; also see claims 34, 39, and 42, methods of emoblization/devascularization comprising embolizing particles and delivering particles in liquid comprising first particles and second particles, wherein the first particles travel more distally in the vascular system…for use with gamma or beta radiation such as iodine-125 or iodine-131);
and a second radioisotope having a second type of ionizing radiation for treatment of a second region of the target location, the second type of ionizing radiation being different than the first type of ionizing radiation;
Fritz et al. disclose a second radioisotope having a second type of ionizing radiation for treatment of a second region of the target location, the second type of ionizing radiation being different than the first type of ionizing radiation (see para [0036],
[0090], [0097], [0116], [0180]-[0183], and [0200]; also see claims 34, 39, and 42, methods of emoblization comprising embolizing particles and delivering particles in liquid comprising first particles and second particles); wherein the second particles travel more proximally in the tissue than the first particles... for use with gamma or beta radiation such as yttirium-90 or iodine-131);
wherein each of the first type of ionizing radiation and the second type of ionizing radiation is selected from the group consisting of: alpha type ionizing radiation, beta type ionizing radiation, gamma type ionizing radiation, and combinations thereof.
Finally, Fritz et al. disclose wherein each of the first type of ionizing radiation and the second type of ionizing radiation is selected from the group consisting of: alpha type ionizing radiation, beta type ionizing radiation (see para [0097] and [0116]), gamma type ionizing radiation (see para [0097] and [0116]), and combinations thereof.
Regarding instant claim 6, Fritz et al. teach wherein the biocompatible prepolymer comprises a cyanoacrylate (see para [0055]).
Regarding instant claim 7, Fritz et al. teach wherein one of the first radioisotope and the second radioisotope comprises one of lodine-125 and lodine-131 (see para [0036], [0090], [0097], [0116], [0180]-[0183], and [0199]-[0200]; also see claims 34, 39, and 42, methods of emoblization/devascularization of tumors comprising embolizing particles and delivering particles in liquid comprising first particles and second particles, wherein the first particles travel more distally in the vascular system of the tumor tissue and the second particles travel more proximally in the tumor tissue for embolization… for use with gamma or beta radiation such as iodine-131.).
Regarding instant claim 8, Fritz et al. teach wherein the target location comprises target tissue (see para [0090], (0102], and [0181]) or a vascular malformation.
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.
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 non-obviousness.
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 1-5 and 9-36 are rejected under 35 U.S.C. 103 as being unpatentable over Fritz et al. in view of Greff et al. (USRE39,456E), Knox (US2014/0134104A1), and Peng et al. (US2007/0053830A1).
[The Examiner is going to introduce each new reference and then combine them where appropriate to reject the instant claims.]
1. Greff et al.
Greff et al. teach radioactive embolizing compositions (see title). Additionally, Greff et al. disclose novel radioactive compositions which are particularly suited for treating solid mass tumors via catheter delivery (see abstract).
2. Knox
Knox teaches cancer therapy (see title). In addition, Knox discloses that the invention provides a method of treating a tumor or other lesion comprising introducing a solution comprising one or more radioactive isotopes directly into said tumour or other
lesion in a mammal to effect in situ precipitation of a radioactive precipitate in the tumour or other lesion (see abstract).
3. Peng et al.
Peng et al. teach particulate materials and compositions for radio therapy (see title). Furthermore, Peng et al. disclose timed-bioresorbable particulates, particularly microspheres or fibers, may be used as a vehicle for delivery of radioisotopes,
such as Y-90 and Pd-103 for localized radiotherapy, or as an embolic device. These particulates may also be embedded in polymers, or dispersed in injectable gels or other injectable media for the treatment of various cancers. The benefit of bioresorption, the ability to control the ratio of radioisotopes in the particulate, especially the gamma and beta ratios such as In-111/Y-90 ratio in a particulate, and the benefit of non-conductive implants are disclosed (see abstract).
The teachings of Fritz et al. are disclosed above within the 35 U.S.C §102 Section.
Ascertaining the Difference
The remainder of the instant claims are not taught by Fritz et al. alone. The combination of Fritz et al., Greff et al., Knox, and Peng et al. are appropriately combined to reject the instant claims.
[The kit claims within instant claims 9-20 are obvious to a skilled artisan (POSITA; person of ordinary skill in the art). The instant claim limitations taught within the composition claims 1-8 and method claims 21-36, have direct application to the kit claims. It would be obvious prior to the effective filing date of the claimed invention to modify the prior art of record by assembling a kit-of-parts based on the composition and method claims for manufacture. The motivation would be to supply the consumer with a liquid radioembolic agent for delivering local radiation to a target location while also causing devascularization at the target location.]
Combination of Fritz et al. and Knox
Regarding instant claims 2 and 12, Fritz et al. and Knox teach wherein the liquid embolic agent comprises a liquid mixture (see para [0097], [0100], and [0205] within Fritz et al.), but does not specifically disclose that the mixture is homogenous.
However, Knox discloses a liquid radioembolic agent (see para [0008] and [0030]-[0032] within Knox) for delivering local radiation to a target location while also causing devascularization at the target location (see para [0008], [0013] and [0043] within Knox), comprising a homogenous liquid mixture (see para [0009], [0011], and [0032] within Knox). To a person of ordinary skill in the art, making the liquid mixture homogeneous as taught by Knox would have been obvious for use with the liquid radioembolic agent mixture as in Fritz et al. in order to improve the precipitation of radioactive materials in a tumor or tissue (see para [0008] within Knox), because Fritz et al. and Knox are directed towards liquid radioembolic agents comprising one or more radioisotopes such as iodine-131 (see para [0116] within Fritz et al.; and see para [0030] within Knox).
Regarding instant claims 3, 11, and 13, Fritz et al. and Knox teach wherein the target location comprises a tumor and the first type of ionizing radiation comprises beta type ionizing radiation and the first region of the tumor comprises a core of the tumor and the second type of ionizing radiation comprises ionizing radiation and the second region of the tumor comprises a periphery of the tumor (see para [0036], [0090], [0097], [0116], [0180]-[0183], and [0199]-[0200]; also see claims 34, 39, and 42, methods of emoblization/ devascularization of tumors comprising embolizing particles and delivering particles in liquid comprising first particles and second particles, wherein the first particles travel more distally in the vascular system of the tumor tissue and the second particles travel more proximally in the tumor tissue for embolization... for use with gamma or beta radiation such as Y-90 or iodine-131; within Fritz et al.), but Fritz et al. does not specifically disclose that the second type of radiation is alpha radiation.
However, Knox discloses a liquid radioembolic agent (see para [0008], [0030]-[0032] within Knox) for delivering local radiation to a target location while also causing devascularization at the target location (see para [0008], [0013], and [0043] within Knox), wherein the target location comprises a tumor (see para [0008] and [0036] within Knox) and ionizing radiation comprises alpha type ionizing radiation (see para [0018], [0020] and [0032] within Knox). To a person of ordinary skill in the art, substituting alpha radiation as taught by Knox would have been obvious for use with the liquid radioembolic agent mixture as in Fritz et al. in order to use desired radioisotopes such as iodine-125 that precipitate in desired locations in the tumor (see para [0031]-[0036] within Knox), because Fritz et al. and Knox are directed towards liquid radioembolic agents comprising one or more radioisotopes such as iodine-131 (see para [0116] within Fritz et al.; and see para [0030] within Knox).
Regarding instant claims 4, 11, and 14, Fritz et al. and Knox teach wherein the target location comprises a tumor and the first type of ionizing radiation comprises alpha type ionizing radiation and the first region of the tumor comprises a core of the tumor and the second type of ionizing radiation comprises beta type ionizing radiation and the second region of the tumor comprises a periphery of the tumor (see para [0036), [0090], (0097], [0116], [0180]-[0183), and [0199]-[0200]; also see claims 34, 39, and 42, methods of emoblization/ devascularization of tumors comprising embolizing particles and delivering particles in liquid comprising first particles and second particles, wherein the first particles travel more distally in the vascular system of the tumor tissue and the second particles travel more proximally in the tumor tissue for embolization… for use with gamma or beta radiation such as Y-90 or iodine-131; within Fritz et al.), but does not specifically disclose that the first type of ionizing radiation is alpha.
However, Knox discloses a liquid radioembolic agent (see para [0008] and [0030]-[0032] within Knox) for delivering local radiation to a target location while also causing devascularization at the target location (see para [0008], [0013], and [0043] within Knox), wherein the target location comprises a tumor (see para [0008] and [0036] within Knox) and ionizing radiation comprises alpha type ionizing radiation (see para [0018], [0020] and [0032] within Knox). To a person of ordinary skill in the art, substituting alpha radiation as taught by Knox would have been obvious for use with the liquid radioembolic agent mixture as in Fritz et al. in order to use desired radioisotopes such as iodine-125 that precipitate in desired locations in the tumor (see para [0031]-[0036] within Knox), because Fritz et al. and Knox are directed towards liquid radioembolic agents comprising one or more radioisotopes such as iodine-131 (see para [0116] within Fritz et al.; and see para [0030] within Knox).
Regarding instant claims 5 and 15, Fritz et al. and Knox teach wherein one of the first radioisotope and the second radioisotope comprises lodine-131 which is both a beta and gamma type emitter (see para [0036], [0090], [0097], [0116], [0180]-[0183], [0199], and [0200]; also see claims 34, 39, and 42, methods of emoblization/ devascularization of tumors comprising embolizing particles and delivering particles in liquid comprising first particles and second particles, wherein the first particles travel more distally in the vascular system of the tumor tissue and the second particles travel more proximally in the tumor tissue for embolization… for use with gamma or beta radiation such as iodine-131; within Fritz et al.).
Regarding instant claim 16, Fritz et al. and Knox teach wherein the biocompatible prepolymer comprises a cyanoacrylate (see para [0055]).
Regarding instant claim 17, Fritz et al. and Knox teach wherein one of the first radioisotope and the second radioisotope comprises one of lodine-125 and lodine-131 (see para [0036], [0090], [0097], [0116], [0180]-[0183], and [0199]-[0200]; also see claims 34, 39, and 42, methods of emoblization/devascularization of tumors comprising embolizing particles and delivering particles in liquid comprising first particles and second particles, wherein the first particles travel more distally in the vascular system of the tumor tissue and the second particles travel more proximally in the tumor tissue for embolization… for use with gamma or beta radiation such as iodine-131.; within Fritz et al.).
Regarding instant claim 9, Fritz et al. and Knox teach an embolization kit for delivering local radiation to a tumor while also causing tumor devascularization due to embolization.
Please see the discussion and citations within instant claim 1-8 for the necessary rejection text.
Regarding instant claim 10, Fritz et al. and Knox teach wherein the first liquid radioembolic agent is loaded within a first microcatheter and the second liquid radioembolic agent is loaded within a second microcatheter.
Please see the discussion and citations within instant claim 1 for the necessary rejection text. Furthermore, Fritz et al. disclose the use of liquid radioembolic agent microcatheters from the syringe contents (see Example 14; paragraph [0031]; and Fig. 8 all within Fritz et al.). A skilled artisan (POSITA) could load a microcatheter within the kit-of-parts with the desired radioembolic agent.
Combination of Fritz et al. and Greff et al.
Regarding instant claim 19, Fritz et al. and Greff et al. teach wherein at least one of the first radioisotope and the second radioisotope comprises from about 0.1 to about 25 weight percent of the respective first liquid radioembolic agent or the second liquid radioembolic agent and has a radioactive content of from about 0.5 microcurie to about 100 millicurie.
Greff et al. disclose wherein at least one of the first radioisotope and the second radioisotope comprises from about 0.1 to about 25 weight percent of the respective first liquid radioembolic agent or the second liquid radioembolic agent and has a radioactive content of from about 0.5 microcurie to about 100 millicurie (see col 10, ln 30-33, within Greff et al.).
Regarding instant claim 21, Fritz et al. and Greff et al. teach a method for embolizing a blood vessel leading to or in a solid mass tumor and causing necrosis to a portion of the solid mass tumor (see col 3, In 36-45 within Greff et al.), the method comprising the steps of: identifying at least one blood vessel that leads to or is in the solid mass tumor (see col 10, In 15-29 within Greff et al.); injecting a first liquid radioembolic agent into the at least one blood vessel, the first liquid radioembolic agent including a biocompatible polymer or prepolymer (see col 4, In 45-62; and col 9, In 60-67 within Greff et al.) and a first radioisotope and being injected into the blood vessel under conditions wherein the polymer or prepolymer polymerizes and forms a solid mass which embolizes the at least one blood vessel (see col 4, In 45-62 within Greff et al.) and further wherein the first radioisotope is employed in an amount effective to cause necrosis of at least a first portion of the tumor (see col 4, In 45-62; and col 5, In 21-33; both within Greff et al.). Greff et al. does not specifically disclose injecting a second liquid radioembolic agent into the at least one blood vessel, the second liquid radioembolic agent including a biocompatible polymer or prepolymer and a second radioisotope and being injected into the blood vessel under conditions wherein the polymer or prepolymer polymerizes and forms a solid mass which embolizes the at least one blood vessel and further wherein the second radioisotope is employed in an amount effective to cause necrosis of at least a second portion of the tumor.
However, Fritz et al. disclose a liquid radioembolic agent for delivering local radiation to a target location while also causing devascularization at the target location (see para [0036], [0090], and [0097]; also see claims 39 and 42, microsphere particles for devascularization of target tissue are placed in suspension liquid ad injected; within Fritz et al.), the liquid radioembolic agent comprising: a biocompatible prepolymer (see Table 1; also see para [0040]-[0042], [0068], and [0072], biocompatible polymers and prepolymers with biological inertness… PMMA monomer; within Fritz et al.); a first radioisotope having a first type of ionizing radiation for treatment of a region of the target location (see para [0036], [0090], [0097], [0116], [0180]-[0183], and [0199]-[0200]; also see claims 34, 39, and 42, methods of emoblization/devascularization comprising embolizing particles and delivering particles in liquid comprising first particles and second particles, wherein the first particles travel more distally in the vascular system... for use with gamma or beta radiation such as iodine-125 or iodine-131; within Fritz et al.); and a second radioisotope having a second type of ionizing radiation for treatment of a region of the target location (see para [0036], [0090], [0097], [0116], [0180]-[0183], and [0200]); also see claims 34, 39, and 42, methods of emoblization comprising embolizing particles and delivering particles in liquid comprising first particles and second particles, wherein the second particles travel more proximally in the tissue than the first particles... for use with gamma or beta radiation such as Y-90 or iodine-131; within Fritz et al.), wherein the second radioisotope is employed in an amount effective to cause necrosis of at least a second portion of the tumor (see para [0184], and [0190], blockage of blood flow at multiple levels throughout the blood supply of the tumor or target tissue; within Fritz et al.). To a person of ordinary skill in the art, substituting a second radioisotope as taught by Fritz et al. for use in the method for embolizing a blood vessel as in Greff et al. would have been obvious in order to treat desired areas of the tumor using radioisotopes that treatment of different regions of the tumor or target location (see para [0036], [0090], [0097], [0116], [0180]-[0183], and [0200]; also see claims 34, 39, and 42, methods of emoblization comprising embolizing particles and delivering particles in liquid comprising first particles and second particles, wherein the second particles travel more proximally in the tissue than the first particles… for use with gamma or beta radiation such as Y-90 or iodine-131; within Fritz et al.), because Fritz et al. and Greff et al. are directed towards liquid radioembolic agents for delivering local radiation to a target location while also causing necrosis at the target location.
Regarding instant claim 22, Fritz et al. and Greff et al. teach wherein the at least one blood vessel includes at least one vascular vessel that leads to the first portion of the tumor and a second portion of the tumor (see para [0152], [0180], and [0199]-[0201], injections in a horizontal direction and a vertical direction of the vascular system.; within Fritz et al.); but does not specifically disclose that the first liquid radioembolic agent being injected into the first vascular pedicle and the second liquid radioembolic agent being injected into the second vascular pedicle.
However, Fritz et al. further discloses varying the size of particles used to deliver the radioisotopes through vasculature of the tumor in order to control the location where the isotopes are delivered to the tumor (see para [0198][0201] within Fritz et al.). To a person of ordinary skill in the art, varying the location of injecting the particles would have been obvious through routine experimentation in order to optimize the volume of isotopes delivered to cause necrosis in the tumor.
Regarding instant claim 23, Fritz et al. and Greff et al. teach wherein the first portion of the tumor comprises a first region and a second region of the tumor comprises a periphery of the tumor (see para [0036], [0090], [0097], [0116], [0180]-[0183], and [0200]; also see claims 34, 39, and 42, methods of emoblization comprising embolizing particles and delivering particles in liquid comprising first particles and second particles, wherein the first particles travel more distally in the vascular system and the second particles travel more proximally In the tissue than the first particles... for use with gamma or beta radiation such as Y-90 or iodine-131; within Fritz et al.); but does not specifically disclose the center of the tumor.
However, Fritz et al. further discloses varying the size of particles used to deliver the radioisotopes In order to control the location where the isotopes are delivered to the tumor (see para [0198]-[0201] within Fritz et al.). To a person of ordinary skill in the art, varying the location of the injection would have been obvious through routine experimentation in order to optimize the amount of isotopes injected to cause necrosis of the tumor.
Regarding instant claim 24, Fritz et al. and Greff et al. teach wherein the first radioisotope is different than the second radioisotope (see para [0036], [0090], [0097], [0116], [0180]-[0183], and [0200]; also see claims 34, 39, and 42, methods of emoblization comprising embolizing particles and delivering particles in liquid comprising first particles and second particles, wherein the second particles travel more proximally in the tissue than the first particles... for use with gamma or beta radiation such as Y-90 or iodine-131; within Fritz et al.).
Regarding instant claim 25, Fritz et al. and Greff et al. teach wherein the first radioisotope has a first type of ionizing radiation and the second radioisotope has a second type of ionizing radiation, wherein each of the first type of ionizing radiation and the second type of ionizing radiation is selected from the group consisting of: alpha type ionizing radiation, beta type ionizing radiation (see para [0097] and [0116] within Fritz et al.), gamma type ionizing radiation (see para [0097] and [0116] within Fritz et al.), and combinations thereof.
Regarding instant claim 29, Fritz et al. and Greff et al. teach wherein the biocompatible prepolymer of each of the first liquid radioembolic agent and the second liquid radioembolic agent comprises cyanoacrylate (see col 7, In 37-48; and col 9, In 35-47; both within Greff et al.).
Regarding instant claim 31, Fritz et al. and Greff et al. teach a method for treatment of a target tissue (see col 3, In 36-45 within Greff et al.) comprising the steps of: identifying at least one first blood vessel that leads to or is in the target tissue (see col 10, In 15-29 within Greff et al.); injecting a first liquid radioembolic agent into the at least one blood vessel, the first liquid radioembolic agent including a biocompatible polymer or prepolymer (see col 4, In 45-62; and col 9, In 60-67 within Greff et al.) and a first radioisotope and being injected into the at least one first blood vessel under conditions wherein the polymer or prepolymer polymerizes and forms a solid mass which embolizes the at least one first blood vessel (see col 4, In 45-62 within Greff et al.) and further wherein the first radioisotope is employed in an amount effective to cause necrosis of at least a first portion of the target tissue (see col 4, In 45-62; and col 5, In 21-33 within Greff et al.); but does not specifically disclose injecting a second liquid radioembolic agent into the at least one first blood vessel or into at least one second blood vessel, the second liquid radioembolic agent including a biocompatible polymer or prepolymer and a second radioisotope and being injected into the at least one first blood vessel or the al least one second blood vessel under conditions wherein the polymer or prepolymer polymerizes and forms a solid mass which embolizes the at least one first blood vessel or the at least one second blood vessel and further wherein the second radioisotope is employed in an amount effective to cause necrosis of at least a second portion of the target tissue.
However, Fritz et al. disclose a liquid radioembolic agent for delivering local radiation to a target location while also causing devascularization al the target location (see para [0036], [0090], and [0097]; also see claims 39 and 42, microsphere particles for devascularization of target tissue are placed in suspension liquid ad injected; within Fritz et al.), the liquid radioembolic agent comprising: a biocompatible prepolymer (see Table 1; also see para [0040]-[0042], [0068], and [0072], biocompatible polymers and prepolymers with biological inertness... PMMA monomer.); a first radioisotope having a first type of ionizing radiation for treatment of a region of the target location (see para [0036], [0090], [0097], [0116], [0180]-[0183], and [0199]-[0200]; also see claims 34, 39, and 42, methods of emoblization/devascularizalion comprising embolizing particles and delivering particles in liquid comprising first particles and second particles, wherein the first particles travel more distally in the vascular system... for use with gamma or beta radiation such as iodine-125 or iodine-131; within Fritz et al.); and a second radioisotope having a second type of ionizing radiation for treatment of a region of the target location (see para [0036], [0090], [0097], [0116], [0180]-[0183], and [0200]; Claims 34, 39, and 42, methods of emoblization comprising embolizing particles and delivering particles In liquid comprising first particles and second particles, wherein the second particles travel more proximally in the tissue than the first particles... for use with gamma or beta radiation such as Y-90 or iodine-131; within Fritz et al.), because Fritz et al. and Greff et al. are directed towards liquid radioembolic agents for delivering local radiation to a target location while also causing necrosis at the target location. Further, regarding the injecting at last a second blood vessel, Fritz et al. further disclose injecting in at least one blood vessel includes at least one vascular vessel that leads to the first portion of the tumor and a second portion of the tumor (see para [0152], [0180], and [0199]-[0201], injections in a horizontal direction and a vertical direction of the vascular system; within Fritz et al.). To a person of ordinary skill in the art, varying the location of the particles would have been obvious through routine experimentation in order to optimize the volume of isotopes injected to cause necrosis in the tumor.
Regarding instant claim 32, Fritz et al. and Greff et al. teach wherein the tissue comprises one of a solid mass tumor (see col 3, In 58-64 within Greff et al.) and a vascular malformation.
Regarding instant claims 20 and 33, Fritz et al. and Greff et al. teach wherein the tumor comprises a brain tumor (col 5, In 39-43); but does not specifically disclose meningioma. To a person of ordinary skill in the art, selecting among known types of brain tumors would have been obvious through routine experimentation in order to optimize treatment of solid mass tumors (col 10, In 4-14 within Greff et al.; also see PTO-892 NPL U).
Combination of Fritz et al., Greff et al., and Knox
Regarding instant claims 18 and 30, Fritz et al., Greff et al., and Knox teach wherein the first radioisotope comprises one of a beta emitter radioisotope selected from the group consisting of: I-125, I-131 (see para [0116] within Fritz et al.), Y-90, Lu-177, and Cu-67 and an alpha emitter radioisotope selected from the group consisting of: Pb-212, Ac-225, Ra-223, and At-211 and the second radioisotope comprises one of a beta emitter radioisotope selected from the group consisting of: I-125, I-131, Y-90 (see para [0116] within Fritz et al.), Lu-177, and Cu-67 and an alpha emitter radioisotope selected from the group consisting of: Pb-212, Ac-225, Ra-223, and At-211. Knox discloses a liquid radioembolic agent (see para [0008], [0030]-[0032] within Knox) for delivering local radiation to a target location while also causing devascularization at the target location (see para [0008], [0013], and [0043] within Knox), wherein the target location comprises a tumor (see para [0008] and [0036] within Knox) and ionizing radiation comprises alpha type ionizing radiation (see para [0018], [0020] and [0032] within Knox). Furthermore, selection of alpha emitters such as Pb-212, Ac-225, Ra-223, and At-211 would be obvious in light of the Knox disclosure. To a person of ordinary skill in the art, using alpha radiation as taught by Knox would have been obvious for use with the liquid radioembolic agent mixture as in Fritz et al. in order to use desired radioisotopes such as iodine-125 that precipitate in desired locations in the tumor (see para [0031]-[0036] within Knox), because Fritz et al. and Knox are directed towards liquid radioembolic agents comprising one or more radio isotopes such as iodine-131 (see para [0116] within Fritz et al.; and see para [0030] within Knox).
Regarding instant claim 26, Fritz et al., Greff et al., and Knox teach wherein the first type of ionizing radiation comprises beta type ionizing radiation and the first portion of the tumor comprises the tumor and the second type of ionizing radiation comprises type ionizing radiation and the second portion of the tumor comprises a periphery of the tumor (see para [0036], [0090], [0097], [0116], [0180]-[0183], and [0199]-[0200]; also see claims 34, 39, and 42, methods of emoblization/devascularization of tumors comprising embolizing particles and delivering particles in liquid comprising first particles and second particles, wherein the first particles travel more distally in the vascular system of the tumor tissue and the second particles travel more proximally in the tumor tissue for embolization... for use with gamma or beta radiation such as Y-90 or iodine-131 within Fritz et al.); but does not specifically disclose that the first portion is the core of a tumor and the second radiation is alpha radiation.
However, Knox discloses a liquid radioembolic agent (see para [0008] and [0030]-[0032] within Knox) for delivering local radiation to a target location while also causing devascularization at the target location (see para [0008], [0013], and [0043] within Knox), wherein the target location comprises a tumor (see para [0008] and [0036] within Knox) and ionizing radiation comprises alpha type ionizing radiation (see para [0018], [0020] and [0032] within Knox). To a person of ordinary skill in the art, substituting alpha radiation as taught by Knox would have been obvious for use with the method for embolizing a blood vessel as in Fritz et al. and Greff et al. in order to use desired radio isotopes such as iodine-125 that precipitate in desired locations in the tumor (see para [0031]-[0036] within Knox), because Fritz et al., Greff et al., and Knox are directed towards liquid radioembolic agents comprising one or more radio isotopes such as iodine or yttrium (see col 7, In 49-63 within Greff et al.; see para [0116] within Fritz et al.; see para [0030] within Knox).
Regarding instant claim 27, Fritz et al., Greff et al., and Knox teach wherein the first type of ionizing radiation comprises type ionizing radiation and the first portion of the tumor comprises a core of the tumor and the second type of ionizing radiation comprises beta type ionizing radiation and the second portion of the tumor comprises a periphery of the tumor (see para [0036], [0090], [0097], [0116], [0180]-[0183], and [0199]-[0200]; also see claims 34, 39, and 42, methods of emoblization/ devascularization of tumors comprising embolizing particles and delivering particles in liquid comprising first particles and second particles, wherein the first particles travel more distally in the vascular system of the tumor tissue and the second particles travel more proximally in the tumor tissue for embolization… for use with gamma or beta radiation such as Y-90 or iodine-131; within Fritz et al.); but does not specifically disclose that the first type of radiation is alpha radiation.
However, Knox discloses a liquid radioembolic agent (see para [0008], [0030]-[0032] within Knox) for delivering local radiation to a target location while also causing devascularization at the target location (see para [0008], [0013], and [0043] within Knox), wherein the target location comprises a tumor (see para [0008] and [0036] within Knox) and ionizing radiation comprises alpha type ionizing radiation (see para [0018], [0020] and [0032] within Knox). To a person of ordinary skill in the art, substituting alpha radiation as taught by Knox would have been obvious for use with the liquid radioembolic agent mixture as in Fritz et al. in order to use desired radioisotopes such as iodine-125 that precipitate in desired locations in the tumor (see para [0031]-[0036] within Knox), because Fritz et al. and Knox are directed towards liquid radioembolic agents comprising one or more radio isotopes such as iodine-131 (see para [0116] within Fritz et al.; see para [0030] within Knox).
Regarding instant claim 28, Fritz et al., Greff et al., and Knox teach wherein one of the first radioisotope and the second radioisotope comprises a beta type emitter and the other of the first radioisotope and the second radioisotope comprises a radiation emitter (see para [0036], [0090], [0097], [0116], [0180]-[0183], and [0199]-[0200]; also see claims 34, 39, and 42, methods of emobIization/devascularization of tumors comprising embolizing particles and delivering particles in Iiquid comprising first particles and second particles, wherein the first particles travel more distally in the vascular system of the tumor tissue and the second particles travel more proximally in the tumor tissue for embolization… for use with gamma or beta radiation such as Y-90 or iodine-131 within Fritz et al.); but does not specifically disclose that the second radiation is alpha radiation.
However, Knox discloses a liquid radioembolic agent (see para [0008] and [0030]-[0032] within Knox) for delivering local radiation to a target location while also causing devascularization at the target location (see para [0008], [0013], and [0043] within Knox), wherein the target location comprises a tumor (see para [0008] and [0036] within Knox) and ionizing radiation comprises alpha type ionizing radiation (see para [0018], [0020], and [0032] within Knox). To a person of ordinary skill in the art, substituting alpha radiation as taught by Knox would have been obvious for use with the liquid radioembolic agent mixture as in Fritz et al. in order to use desired radio isotopes such as iodine-125 that precipitate in desired locations in the tumor (see para [0031]-[0036] within Knox), because Fritz et al. and Knox are directed towards liquid radioembolic agents comprising one or more radioisotopes such as iodine-131 (see para [0116] within Fritz et al.; and see para [0030] within Knox).
Combination of Fritz et al., Greff et al., and Peng et al.
Regarding instant claim 34, Fritz et al., Greff et al., and Peng et al. teach wherein at least one of the first liquid radioembolic agent and the second liquid radioembolic agent includes a gamma emitter radioisotope (see para [0036], [0090], [0097], [0116],
[0180]-[0183], and [0199]-[0200]; also see claims 34, 39, and 42, methods of emoblization/devascularization of tumors comprising embolizing particles and delivering particles in liquid comprising first particles and second particles, wherein the first particles travel more distally in the vascular system of the tumor tissue and the second particles travel more proximally in the tumor tissue for embolization... for use with gamma or beta radiation such as Y-90 or iodine-131; within Fritz et al.); but does not specifically disclose performing subsequent confirmatory imaging and precise computation of dosimetry.
However, Peng et al. disclose a method for embolizing a blood vessel leading to or in a solid mass tumor (see para [0029], [0031], and [0034] within Peng et al.), comprising injecting a first liquid radioembolic agent into the at least one blood vessel (see para [0042] within Peng et al.), the first liquid radioembolic agent including a biocompatible polymer or prepolymer (see para [0044] within Peng et al.), comprising performing subsequent confirmatory imaging and precise computation of dosimetry (see Fig. 6; and para [0025], [0034]-[0035], [0065], [0089], and [0119], confirming radio-trace activity distribution and dose confirmation that is calculated based on retention of radio isotope through time for individual mini-infusions and cumulative total dose; within Peng et al.). To a person of ordinary skill in the art, performing imaging as taught by Peng et al. would have been obvious for use in the method for embolizing a blood vessel leading to or in a solid mass tumor as in Fritz et al. or Greff et al. in order to provide radiotraceability and diagnostics to control injection activity and dose fraction through time (see para [0034] within Peng et al.), because Fritz et al., Greff et al., and Peng et al. are directed towards method for embolizing a blood vessel leading to or in a solid mass tumor.
Regarding instant claim 35, Fritz et al., Greff et al., and Peng et al. teach further including the step of using a gamma radiation in real time to image a distribution of radiation within the target tissue (see para [0031], [0034], [0080]-[0081], gamma tracers to provide real-time distribution; within Peng et al.); but does not specifically disclose using a camera.
However, Peng further discloses radiographical detection (see para [0011] within Peng et al.). To a person of ordinary skill in the art, selecting among known types of imaging detection devices (such as a camera) would have been obvious through routine experimentation in order to optimize real-time monitoring of the tissue for dosimetry control (see para [0034] within Peng et al.).
Regarding instant claim 36, Fritz et al., Greff et al., and Peng et al. teach further including the step of obtaining a plurality of gamma images over a predetermined period of time to determine and observe radiation levels over the predetermined period of time (see para [0031], [0034], and [0080]-[0081], gamma tracers to provide real-time distribution; within Peng et al.) and using the plurality of gamma images to perform dosimetric calculations (see Fig. 6; and para [0025], [0034]-[0035], [0065], [0089], and [0119], confirming radio-trace activity distribution and dose confirmation that is calculated based on retention of radio isotope through time for individual mini-infusions and cumulative total dose; within Peng et al.); but does not specifically disclose imaging using a camera.
However, Peng further discloses radiographical detection (see para [0011] within Peng et al.). To a person of ordinary skill in the art, selecting among known types of imaging detection devices (such as a camera) would have been obvious through routine experimentation in order to optimize real-time monitoring of the tissue for dosimetry control (see para [0034] within Peng et al.).
Analogous Art
The Fritz et al., Greff et al., Knox, and Peng et al. references are directed to the same field of endeavor as the instant claims, that is, a liquid radioembolic agent for delivering local radiation to a target location while also causing devascularization at the target location, as disclosed within instant claim 1.
Obviousness Analysis
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the radioembolic composition disclosed by Fritz et al., using the teachings of Greff et al., Knox, and Peng et al. references in order to arrive at the subject matter of the instant claims.
The Fritz et al., Greff et al., Knox, and Peng et al. references all have considerable overlap in the radioembolic arts. In this instance, Fritz et al. supplies the template for the radioembolic composition, Greff et al. supplies numerous radioactive embolizing examples, Knox supplies a general cancer therapy disclosure that uses radioactive isotopes, while Peng et al. supplies claim-specific details pertaining to radio therapy (embolic device). All references are directed to radioembolic compositions and therefore constitute analogous art under MPEP §2141.01(a). A POSITA would have reasonably consulted the four references when seeking to develop a radioembolic composition.
Given these teachings, a POSITA would have been motivated to combine the template for the radioembolic composition as disclosed by Fritz et al., the required radioactive embolizing details supplied by Greff et al., the general cancer therapy disclosure that uses radioactive isotopes taught by Knox, and the claim-specific details of radio therapy disclosed by Peng et al.
The modification constitutes a simple substitution of one known element for another to obtain a predictable result [MPEP §2143(I)(B)].
The combination represents the use of a known technique to improve a similar composition in the same way [MPEP §2143(I)(C)].
The art provides a finite number of identified, predictable solutions, and the POSITA would have pursued the claimed configuration with a reasonable expectation of success [MPEP §2143(I)(E); KSR].
The combination of the radioembolic composition taught by Fritz et al. along with the use of the necessary claim limitations taught by Greff et al., Knox, and Peng et al. would allow a research and development scientist (POSITA) to develop the invention taught in the instant application.
Furthermore, the additional claim limitations taught by Greff et al., Knox, and Peng et al. would have been viewed by a POSITA as routine design optimizations or known modifications for radioembolic compositions. The motivation would be to supply the consumer with a liquid radioembolic agent for delivering local radiation to a target location while also causing devascularization at the target location. Implementing these features in Fritz et al.’s radioembolic compositions would not require more than ordinary skill or routine experimentation.
Accordingly, the combination of Fritz et al., Greff et al., Knox, and Peng et al. provides all the elements of the claimed invention. The resulting enhanced radioembolic compositions, constitute no more than the predictable outcome of combining familiar prior art components, and therefore the claimed subject matter would have been obvious to a POSITA prior to the effective filing date of the invention.
Conclusion
No claims are allowed.
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/JOHN W LIPPERT III/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
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