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 1-41 are pending in this office action. All pending claims are under examination.
Priority
The current application was filed on September 30, 2024 and is a 371 of PCT/US2023/018445 filed on April 13, 2025, which in turn claims domestic priority to provisional patent application 63/337,773 and 63/330,389 filed on May 3, 2022, and April 13, 2022.
Information Disclosure Statement
Receipt of the Information Disclosure Statements filed on September 30, 2024, February 17, 2026, March 25, 2026, and June 24, 2026 are acknowledged. A signed copy of the four documents are attached to this office action.
Claim Objections
Claims 12, 14, 20, and 22 are objected to because of the following informalities:
Claim 12: Please delete “(Y-90)” to make the claim consistent with the other element, Holmium-166. Also, please use a lowercase “h” to describe the radioisotope “holmium-166.”
Claim 14: Please amend in, “or” prior to the last group member.
Claim 20: Please delete the hyphen (-) and amend in the text “to.”
Claim 22: Please delete the “and” after the phrase “an outer layer…”, and amend it in after the phrase “a liquid containing…”.
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 22-24, 26, 34, and 37-40 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Koole (US2020/0397766A1).
Koole teaches porous embolization microspheres comprising drugs (see title). Also, Koole discloses the current invention provides a method of forming polymeric
microspheres loaded with therapeutic agent, comprising: a. exposing porous polymeric microspheres to an organic solvent comprising a dissolved therapeutic agent thereby creating microspheres loaded with therapeutic agent, b. separating the microspheres loaded with therapeutic agent from the organic solvent, c. washing the microspheres
loaded with therapeutic agent with water, and d. drying the washed microspheres. The microspheres are particularly useful in embolization therapy.
Regarding instant claim 22, Koole teaches a kit for treatment of tumor cells, the kit comprising, a plurality of embolic particles, each embolic particle including, an inner core having a volume within which a radioisotope can be accommodated, the inner core including a surface over which a layer can be arranged; an outer layer having a thickness within which a therapeutic can be accommodated, the outer layer being placed over the surface of the inner core; and the inner core and outer layer having a combined density sufficient to allow an embolic particle to move with a fluid flow, along a pathway, while the embolic particle includes a dimension that is sufficiently large to engage the pathway to limit fluid flow to the tumor cells; a liquid containing the therapeutic and into which the plurality of embolic particles can be soaked to permit the therapeutic to be infused in the outer layer; a vial to accommodate the liquid.
Koole discloses a kit for treatment of tumor cells (kit for treatment of tumor cells; see paragraphs [0027] and [0031]), the kit comprising, a plurality of embolic particles (plurality of embolic microspheres (small spherical particles); see paragraphs [0024] and [0027]), each embolic particle including, an inner core having a volume within which a radioisotope can be accommodated [inner core having pores or cavities (volume within which a radioisotope can be accommodated; see paragraph [0059]], the inner core including a surface over which a layer can be arranged (inner core covered by a surface layer arranged; see paragraph [0059]); an outer layer having a thickness within which a therapeutic can be accommodated (surface layer having pores or cavities (thickness) within which a therapeutic is accommodated; see paragraphs [0059]-[0060]), the outer layer being placed over the surface of the inner core (surface layer (outer layer) is placed over the surface of the core (inner); see paragraph [0059]); and the inner core and outer layer having a combined density sufficient to allow an embolic particle to move with a fluid flow, along a pathway, while the embolic particle includes a dimension that is sufficiently large to engage the pathway to limit fluid flow to the tumor cells (the inner core and surface layer of the embolic microsphere (small spherical particles) moves through blood to the tumor vascular bed (combined density sufficient to allow an embolic particle to move with a fluid flow, along a pathway) where the embolic microsphere (particle) has a dimension that is sufficiently large to engage the pathway to limit blood flow to tumor cells; see paragraphs [0025], [0048], [0059], and [0068]); a liquid containing the therapeutic and into which the plurality of embolic particles can be soaked to permit the therapeutic to be infused in the outer layer (a liquid containing a therapeutic and into which the plurality of embolic microspheres (particles) are allowed to soak to permit the therapeutic to be infused in the outer layer; see paragraphs [0032[-[0033] and [0097]-[0099]); a vial to accommodate the liquid (centrifuge tube (vial) to accommodate the liquid; see paragraphs [0098]-[0099]).
Regarding instant claim 23, Koole teaches wherein the liquid is disposed in the vial.
Koole discloses wherein the liquid is disposed in the vial (liquid is disposed in a centrifuge tube (vial); see paragraphs [0098]-[0099]).
Regarding instant claim 24, Koole teaches wherein the therapeutic is infused into the outer layer of the plurality of embolic particles when the plurality of embolic particles are disposed in the liquid.
Koole discloses wherein the therapeutic is infused into the outer layer of the plurality of embolic particles when the plurality of embolic particles are disposed in the liquid (therapeutic is absorbed (infused) surface layer (outer layer) of a plurality of microparticles (embolic particles) when the plurality of microparticles (embolic particles) are disposed in a liquid; see paragraphs [0032]-[0033], [0093], and [0097]-[0099]).
Regarding instant claim 26, Koole teaches wherein the plurality of embolic particles expand in size when the plurality of embolic particles are disposed in the liquid.
Koole discloses wherein the plurality of embolic particles expand in size when the plurality of embolic particles are disposed in the liquid (plurality of embolic microspheres (small spherical particles) expand in size with the plurality of embolic particles are disposed in the liquid; see paragraphs [0038]-[0039]).
Regarding instant claim 34, Koole teaches a method of treatment of tumor cells using embolic particles, the method comprising, providing a plurality of embolic particles each having an inner core having a volume within which a radioisotope can be accommodated and an outer layer having a thickness within which a therapeutic can be accommodated; identifying a site of interest that includes the tumor cells to be treated, and delivering the embolic particles to a lumen and allowing the plurality of embolic particles to move with a fluid flow, along a pathway, to the site of interest such that the embolic particles engage with the pathway to limit fluid flow to the tumor cells.
Koole discloses a method of treatment of tumor cells using embolic particles (method of treatment of tumor cells using embolic microspheres (small spherical particles); see paragraphs [0031] and [0068]), the method comprising, providing a plurality of embolic particles each having an inner core having a volume within which a radioisotope can be accommodated and an outer layer having a thickness within which a therapeutic can be accommodated (providing a plurality of embolic microsphere (small spherical particles) each having a core (inner core) with pores or cavities (volume within which a radioisotope can be accommodated and a surface layer (outer layer) having pores or cavities (thickness) which a therapeutic is accommodated; see paragraph [0059]) identifying a site of interest that includes the tumor cells to be treated (identifying a site of interest that includes the tumor cells to be treated; see paragraph [0068]); and delivering the embolic particles to a lumen and allowing the plurality of embolic particles to move with a fluid flow, along a pathway, to the site of interest such that the embolic particles engage with the pathway to limit fluid flow to the tumor cells (delivering the embolic microspheres (particles) via an artery for embolization therapy to block blood flow to the tumor vascular bed (embolic particles to a lumen and allowing the plurality of embolic particles to move with a fluid flow, along a pathway, to the site of interest such that the embolic particles engage with pathway to limit fluid flow to the tumor cells); see paragraphs [0068]-[0069]).
Regarding instant claim 37, Koole teaches further comprising impregnating the therapeutic into respective outer layers of the plurality of embolic particles.
Koole discloses further comprising impregnating the therapeutic into respective outer layers of the plurality of embolic particles (plurality of embolic microspheres (particles) are allowed to soak (impregnating) with a therapeutic in the outer layers; see paragraphs [0032]-[0033] and [0097]-[0099]).
Regarding instant claim 38, Koole teaches wherein the impregnating step further comprising, disposing the plurality of embolic particles into a fluid containing the therapeutic to infuse the therapeutic into at least the outer layer.
Koole discloses further wherein the impregnating step further comprising, disposing the plurality of embolic particles into a fluid containing the therapeutic to infuse the therapeutic into at least the outer layer (disposing the plurality of embolic particles into a liquid containing the therapeutic to soak (infuse) the therapeutic into at least the outer layer; see paragraphs [0032]-[0033] and [0097]-[0099]).
Regarding instant claim 39, Koole teaches wherein a dimension of respective embolic particles limits movement of the respective embolic particles through the lumen at the site of interest to prevent the plurality of embolic particles from migrating away from the site of interest.
Koole discloses further wherein a dimension of respective embolic particles limits movement of the respective embolic particles through the lumen at the site of interest to prevent the plurality of embolic particles from migrating away from the site of interest (dimension of respective embolic microspheres (small spherical particles) limits movement of the respective embolic microspheres through the artery (lumen at the site of interest to prevent the plurality of embolic microspheres from migrating away from the site (embolization therapy); see paragraphs [0025] and [0068]-[0069]).
Regarding instant claim 40, Koole teaches wherein the delivering step includes delivering the plurality of embolic particles through an arterial branch that feeds the tumor cells.
Koole discloses further wherein the delivering step includes delivering the plurality of embolic particles through an arterial branch that feeds the tumor cells (delivering step includes delivering the plurality of embolic microsphere (small spherical particles) through an arterial branch that feeds the tumor cells; see paragraphs [0068]-(0069]).
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 1-22, 25, 27-36, and 41 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (CN111603575A) in view of Gao et al. (CN111840586A), Koole, DiCarlo et al. (US2009/0068271A1), Fritz et al. (WO2009/067105A1), Reb et al. (US11,229,604B2 published in January 2022), and Vogel et al. (US9,308,169B2).
[The Examiner is going to introduce each new reference and then combine them where appropriate to reject the instant claims.]
1. Zhang et al.
Zhang et al. is the closest prior art to the present invention as it teaches radioactive embolization microsphere with a core-shell structure and preparation method and application thereof (see title). Furthermore, Zhang et al. disclose that the invention provides a radioactive embolization microsphere with a core-shell structure. The microsphere with the core-shell structure is formed by taking a biodegradable high polymer material as a shell and wrapping radionuclide as an inner core. According to the biodegradable radioactive embolization microsphere with the core-shell structure provided by the invention, radionuclide is wrapped in the microsphere by a biodegradable polymer shell with the thickness of 1-30 microns. Due to the fact that the polymer shell is thick and all radionuclides are located in the centers of the microspheres, damage to the surface layer of the polymer shell cannot cause leakage of the radionuclides. After the treatment is finished, the nuclide loses radioactivity, and the embolization microsphere is gradually dissolved due to the biodegradable characteristic of the shell, so that the blood vessel in the treatment area is dredged again. In addition, the microsphere with the core-shell structure has a certain proportion of cavities (5%-80% v/v), and the overall density of the microsphere is closer to the density of water, so that the microsphere has better dispersity (see abstract).
2. Gao et al.
Gao et al. teach biodegradable radioactive particle, particle composition and preparation method thereof (see title). In addition, Gao et al. disclose that the invention provides a biodegradable radioactive particle, a particle composition and a preparation method thereof. The radioactive particle comprises a radioactive inner core and a shell, wherein the radioactive inner core comprises radionuclide and alginate hydrogel; and the shell is made of polycaprolactone. The radioactive particle has the advantages of complete degradation in vivo, convenience in clinical use, capability of simultaneously realizing radioactive ray treatment and medicine local treatment, high preparation efficiency, capability of realizing continuous large-scale full-automatic production, full-closed preparation process, capability of preparing radioactive particles meeting the clinical requirements of complex lesion conditions, and the like (see abstract).
3. DiCarlo et al.
DiCarlo et al. teach embolization particles (see title). Additionally, DiCarlo et al. disclose embolic particles, embolic particle chains, and methods for making embolic particles and embolic particle chains are described (see abstract).
4. Fritz et al.
Fritz et al. teach loadable polymeric particles for enhanced imaging in clinical applications and methods of preparing and using the same (see title). Furthermore, Fritz et al. disclose 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).
5. Reb et al.
Reb et al. teach microspheres containing therapeutic agents and related
methods of use (see title). In addition, Reb et al. disclose microspheres, compositions including the microspheres, and methods of using the microspheres are disclosed herein. The microspheres can be substantially spherical and can include a copolymer of a monomer (such as an acrylic monomer) and a cyclodextrin or a derivative thereof. The microspheres can also include a therapeutic agent, such as a platinum-based drug (see abstract).
6. Vogel et al.
Vogel et al. teach microspheres for active embolization (see title). Additionally, Vogel et al. disclose that the present invention relates to injectable compositions comprising biocompatible, swellable, substantially hydrophilic, non-toxic and substantially spherical polymeric material carriers which are capable of efficiently delivering bioactive therapeutic factor(s) for use in embolization drug therapy
The present invention further relates to methods of embolization gene therapy, particularly for the treatment of angiogenic and non-angiogenic-dependent diseases, using the injectable compositions (see abstract).
Combination of Zhang et al. and Gao et al.
Regarding instant claim 1, Zhang et al. and Gao et al. teach an embolic particle for use in treatment of tumor cells. The necessary citations of Zhang et al. as evidenced by Gao et al. that pertain to instant claim 1 are presented in Table I.
Table I
Instant Claim 1
Zhang et al. and Gao et al. Citations
An embolic particle for use in treatment of tumor cells, the embolic particle comprising:
Zhang et al. disclose an embolic particle for use in treatment of tumor cells (embolic microspheres (small spherical particles) (see paragraphs [0008] and [0015] within Zhang et al.).
an inner core having a volume within which a radioisotope can be accommodated, the inner core including a surface over which a layer can be arranged;
Additionally, Zhang et al. disclose the embolic particle comprising: an inner core having a volume within which a radioisotope can be accommodated (inner core having a volume within which a radionuclide (radioisotope) is accommodated (see Figure 1; and paragraphs [0008] and [0010] within Zhang et al.), the inner core including a surface over which a layer can be arranged (inner core has a surface over which a layer is arranged; see Figure 1, and paragraphs ([0008] and [0010] within Zhang et al.);
an outer layer having a thickness within which a therapeutic can be accommodated, the outer layer being placed over the surface of the inner core;
Zhang et al. disclose an outer layer having a thickness within which a therapeutic can be accommodated (polymer shell (outer layer) of 1-30 microns (thickness) (see paragraphs ([0008] and [0010] within Zhang et al.).
Zhang et al. does not disclose a therapeutic drug within the biodegradable polymer. However, Gao et al. is in the biodegradable radioactive polymer arts.
Gao et al. disclose that a polymer shell accommodates a therapeutic; see paragraphs [0009], [0011], and [0044]); also see Figure 1, paragraphs [0008] and [0010] within Gao et al.), the outer layer being placed over the embolic particle to move with a fluid flow (the microsphere (particles) with a core-shell structure (inner core and outer layer).
and the inner core and outer layer having a combined density sufficient to allow the embolic particle to move with a fluid flow, along a pathway, while the embolic particle includes a dimension that is sufficiently large to engage the pathway to limit fluid flow to the tumor cells.
Zhang et al. disclose the embolic particle has an overall density that allows the microsphere (particle) to disperse in blood (move with a fluid flow); see paragraph [0027] within Zhang et al., along a pathway (blood vessel in a tumor (along a pathway); see paragraphs [0004] and [0027] within Zhang et al.), while the embolic particle includes a dimension that is sufficiently large to engage the pathway to limit fluid flow to the tumor cells (embolic microsphere (particle) includes core-shell thickness of 20-35 microns (dimension) that is sufficiently large to engage the blood vessel in the tumor (inherently limits fluid flow); see paragraphs [0004], [0008], [0027], and [0036] within Zhang et al.).
It would have been obvious to one of ordinary skill in the art to combine the teachings of Zhang et al. and Gao et al. prior to the effective filing date of the claimed invention. Both references are pertaining to radionuclide particles comprising an inner core and an outer shell making them analogous art to the skilled artisan. The motivation to combine the two references would be to create an embolic agent with a therapeutic drug that can be embedded within the outer biodegradable polymeric shell.
Regarding instant claim 2, Zhang et al. and Gao et al. teach wherein the dimension of the embolic particle is sufficient to substantially block the fluid flow through the pathway to the tumor cells.
Zhang et al. disclose wherein the dimension of the embolic particle is sufficient to substantially block the fluid flow through the pathway to the tumor cells (20-35 microns core embolic microsphere (small spherical particle) is sufficient to substantially block the blood flow through the pathway to the tumor cells (see paragraphs [0004], [0008], [0027], and [0036] within Zhang et al.).
Regarding instant claim 3, Zhang et al. and Gao et al. teach wherein the embolic particle treats at least one of primary or metastatic tumors of a liver, lungs, the brain or spinal cord, prostate, breast, esophagus, upper aerodigestive tract including the nasopharynx, nasal cavity, oral cavity, oropharynx, hypopharynx, larynx, neck, thyroid, lungs, mediastinum, stomach, small bowel, large bowel, pancreas, spine, kidneys, ureters, bladder, urethra, vagina, uterus, cervix, ovary, lymph nodes, muscles, and bones.
Zhang et al. disclose wherein the embolic particle treats at least one of primary or metastatic tumors of a liver (hepatocellular carcinoma (primary tumor of the liver); see paragraph [0004] within Zhang et al.).
Regarding instant claim 4, Zhang et al. and Gao et al. teach wherein the therapeutic is infused in the outer layer.
Gao et al. disclose wherein the therapeutic is infused in the outer layer (therapeutic agent is added (infused) to the outer shell (layer); see paragraph [0074] within Gao et al.).
It would have been obvious to one skilled in the art, prior to the effective filing date of the claimed invention, to have modified the embolic particle, as disclosed by Zhang et al., to provide the embolic particle wherein the therapeutic is infused in the outer layer, as disclosed by Gao et al., for the benefit that radioactive particles with an inner core containing a radionuclide (radioisotope) and an outer shell (layer) containing a therapeutic are used to provide simultaneous radioactive and local drug treatment of malignant tumor cells (see paragraphs [0004], [0008], [0044], and [0080] within Gao et al.).
Regarding instant claim 5, Zhang et al. and Gao et al. teach wherein the outer layer releases the therapeutic to the tumor cells while the embolic particle limits the fluid flow to the tumor cells.
Zhang et al. disclose while the embolic particle limits the fluid flow to the tumor cells (the embolic microsphere (small spherical particle) limits the blood flow to the tumor cells; see paragraphs [0004], [0008], and [0027] within Zhang et al.), but Zhang et al. does not disclose wherein the outer layer releases the therapeutic to the tumor cells. However, Gao et al. disclose wherein the outer layer releases the therapeutic to the tumor cells (the outer shell (layer) releases the therapeutic to the tumor cells; see paragraphs [0071] and [0080] within Gao et al.).
It would have been obvious to one skilled in the art, prior to the effective filing date of the claimed invention to have modified the embolic particle, as disclosed by Zhang et al., to provide the embolic particle wherein the outer layer releases the therapeutic to the tumor cells, as disclosed by Gao et al., for the benefit that radioactive particles with an inner core containing a radionuclide (radioisotope) and an outer shell (layer) containing a therapeutic that is released from the shell to provide local treatment of malignant tumor cells (see paragraphs [0004], [0008], [0044], and [0080] within Gao et al.).
Regarding instant claim 6, Zhang et al. and Gao et al. teach wherein the embolic particle treats at least one of primary or metastatic tumors of a liver, lungs, the brain or spinal cord, prostate, breast, esophagus, upper aerodigestive tract including the nasopharynx, nasal cavity, oral cavity, oropharynx, hypopharynx, larynx, neck, thyroid, lungs, mediastinum, stomach, small bowel, large bowel, pancreas, spine, kidneys, ureters, bladder, urethra, vagina, uterus, cervix, ovary, lymph nodes, muscles, and bones.
Zhang et al. disclose wherein the embolic particle treats at least one of primary or metastatic tumors of a liver (hepatocellular carcinoma (primary tumor of the liver); see paragraph [0004] within Zhang et al.).
Regarding instant claim 7, Zhang et al. and Gao et al. teach wherein the inner core is embedded with a radioisotope.
Zhang et al. disclose wherein the inner core is embedded with a radioisotope (inner core is embedded with a radionuclide (radioisotope); see abstract within Zhang et al.).
Regarding instant claim 8, Zhang et al. and Gao et al. teach wherein the inner core emits radiation, while the embolic particle limits the fluid flow, to irradiate the tumor cells.
Zhang et al. disclose wherein the inner core emits radiation (inner core emits radiation; see paragraph [0016] within Zhang et al.), while the embolic particle limits the fluid flow (embolic microsphere (small spherical particle) limits blood flow; see paragraphs [0008] and [0027] within Zhang et al.), to irradiate the tumor cells (to irradiate the tumor cells; see paragraphs [0004], [0008] and [0027] within Zhang et al.).
Regarding instant claim 9, Zhang et al. and Gao et al. teach wherein the embolic particle treats at least one of primary or metastatic tumors of a liver, lungs, the brain or spinal cord, prostate, breast, esophagus, upper aerodigestive tract including the nasopharynx, nasal cavity, oral cavity, oropharynx, hypopharynx, larynx, neck, thyroid, lungs, mediastinum, stomach, small bowel, large bowel, pancreas, spine, kidneys, ureters, bladder, urethra, vagina, uterus, cervix, ovary, lymph nodes, muscles, and bones.
Zhang et al. disclose wherein the embolic particle treats at least one of primary or metastatic tumors of a liver (hepatocellular carcinoma (primary tumor of the liver): see paragraph [0004] within Zhang et al.).
Regarding instant claim 10, Zhang et al. and Gao et al. teach wherein the inner core is embedded with a radioisotope and a therapeutic is impregnated in the outer layer.
Zhang et al. disclose wherein the inner core is embedded with a radioisotope (inner core is embedded with a radionuclide (radioisotope); see abstract within Zhang et al.), but Zhang et al. does not disclose wherein a therapeutic is impregnated in the outer layer. However, Gao et al. disclose wherein a therapeutic is impregnated in the outer layer (therapeutic agent is added (impregnated) in the outer shell (layer); see paragraph [0074] within Gao et al.).
It would have been obvious to one skilled in the art, prior to the effective filing date of the claimed invention to have modified the embolic particle, as disclosed by Zhang et al., to provide the embolic particle wherein a therapeutic is impregnated in the outer layer, as disclosed by Gao et al., for the benefit that radioactive particles with an inner core containing a radionuclide (radioisotope) and an outer shell (layer) containing a therapeutic are used to provide simultaneous radioactive ray and local drug treatment of malignant tumor cells (see paragraphs [0004], [0008], [0044], and [0080] within Gao et al.).
Regarding instant claim 11, Zhang et al. and Gao et al. teach wherein while the embolic particle limits the fluid flow to the tumor cells, the inner core emits radiation to kill the tumor cells, and the outer layer releases the therapeutic to treat remaining tumor cells.
Zhang et al. disclose wherein while the embolic particle limits the fluid flow to the tumor cells (the embolic microsphere (small spherical particle) limits the blood flow to the tumor cells; see paragraphs [0004], [0008], and [0027] within Zhang et al.), the inner core emits radiation to kill the tumor cells (inner core emits radiation to kill the tumor cells; see paragraphs [0004], [0008], [0016], and [0027] within Zhang et al.), but Zhang et al. does not disclose wherein the outer layer releases the therapeutic to treat remaining tumor cells. However, Gao et al. disclose wherein the outer layer releases the therapeutic to treat remaining tumor cells (the outer shell (layer) releases the therapeutic to treat the complex tumor cells (inherently treats remaining tumor cells); see abstract; also see paragraphs [0071] and [0080] within Gao et al.).
It would have been obvious to one skilled in the art, prior to the effective filing date of the invention to have modified the embolic particle, as disclosed by Zhang et al., to provide the embolic particle wherein the outer layer releases the therapeutic to treat remaining tumor cells, as disclosed by Gao et al., for the benefit that radioactive particles with an inner core containing a radionuclide (radioisotope) and an outer shell (layer) containing a therapeutic that is released from the shell to provide local treatment of complex malignant tumor cells (see abstract; also see paragraphs [0004], [0008], [0044], and [0080] within Gao et al.).
Regarding instant claim 12, Zhang et al. and Gao et al. teach wherein the radioisotope includes yttrium-90 (Y-90) or Holmium-166.
Zhang et al. disclose wherein the radioisotope includes yttrium-90 (Y-90) (yttrium-90; see paragraphs [0036] and [0045] within Zhang et al.) or Holmium-166 (Holmium-166; see paragraphs [0036] and [0048] within Zhang et al.).
Regarding instant claim 13, Zhang et al. and Gao et al. teach wherein the embolic particle treats at least one of primary or metastatic tumors of a liver, lungs, the brain or spinal cord, prostate, breast, esophagus, upper aerodigestive tract including the nasopharynx, nasal cavity, oral cavity, oropharynx, hypopharynx, larynx, neck, thyroid, lungs, mediastinum, stomach, small bowel, large bowel, pancreas, spine, kidneys, ureters, bladder, urethra, vagina, uterus, cervix, ovary, lymph nodes, muscles, and bones.
Zhang et al. disclose wherein the embolic particle treats at least one of primary or metastatic tumors of a liver (hepatocellular carcinoma (primary tumor of the liver); paragraph [0004] within Zhang et al.).
Combination of Zhang et al., Gao et al., and DiCarlo et al.
Regarding instant claim 14, Zhang et al., Gao et al., and DiCarlo et al. teach wherein the inner core is formed from at least one of a polymer, ceramic, glass, a glass-ceramic composite.
Zhang et al. and Gao et al., in combination, do not disclose wherein the inner core is formed from at least one of a polymer, ceramic, glass, a glass-ceramic composite. However, DiCarlo et al. disclose wherein the inner core is formed from at least one of a polymer (inner core is formed from a polymer; see paragraph [0022] within DiCarlo et al.).
It would have been obvious to one skilled in the art, prior to the effective filing date to have modified the embolic particle, as disclosed by Zhang et al. and Gao et al., to provide the embolic particle discloses wherein the inner core is formed from at least one of a polymer, as disclosed by DiCarlo et al., for the benefit that a polymer inner core and an outer layer is used to prepare embolic particles that contain radioisotopes to treat tumors (see paragraphs [0003], [0022], [0111], and [0121] within DiCarlo et al.).
Regarding instant claim 15, Zhang et al., Gao et al., and DiCarlo et al. teach wherein the inner core is sintered with a porosity of about 10% to about 75%.
Zhang et al. disclose wherein the inner core is sintered with a porosity of about 10 percent to about 75 percent (cavity of microsphere with core-shell structure (inner core is sintered) with a porosity of 5 to 80 percent; see paragraph [0027] within Zhang et al.).
Combination of Zhang et al. and Gao et al.
Regarding instant claim 16, Zhang et al. and Gao et al. teach wherein the outer layer forms a uniform shape about the inner core.
Zhang et al. disclose wherein the outer layer forms a uniform shape about the inner core (shell forms a microsphere (small spherical particle) form a uniform shape about the inner core; see paragraph [0008] within Zhang et al.).
Regarding instant claim 17, Zhang et al. and Gao et al. teach wherein the outer layer is formed from a polymer.
Zhang et al. disclose wherein the outer layer is formed from a polymer (outer shell (outer layer) is formed from a polymer; see paragraph [0008] within Zhang et al.).
Combination of Zhang et al., Gao et al., and Fritz et al.
Regarding instant claim 18, Zhang et al., Gao et al., and Fritz et al. teach wherein the outer layer is embedded with a radiopaque material.
Zhang et al. and Gao et al., in combination, do not disclose wherein the outer layer is embedded with a radiopaque material. However, Fritz et al. disclose wherein the outer layer is embedded with a radiopaque material (outer layer is embedded with a radiopaque material; see paragraph [0075] within Fritz et al.).
It would have been obvious to one skilled in the art, prior to the effective filing date of the invention to have modified the embolic particle, as disclosed by Zhang et al. and Gao et al., to provide the embolic particle wherein the outer layer is embedded with a radiopaque material, as disclosed by Fritz et al., for the benefit that particles coated with a radio-opaque barium sulfate aids in visualization of the finished particles when in use for embolization (see paragraphs [0075] and [0086] within Fritz et al.).
Combination of Zhang et al. and Gao et al.
Regarding instant claim 19, Zhang et al. and Gao et al. teach wherein the embolic particle has a substantially spherical shape.
Zhang et al. disclose wherein the embolic particle has a substantially spherical shape (embolic microsphere is a small spherical particle (substantially spherical); see paragraph [0008] and Figure 1; both within Zhang et al.).
Regarding instant claim 20, Zhang et al. and Gao et al. teach wherein the embolic particle has a size of about 15 micrometers - about 1000 micrometers.
Zhang et al. disclose wherein the embolic particle has a size of about 15 micrometers - about 1000 micrometers (embolic microsphere (particle) has a size of 20 to 35 micrometers; see paragraphs [0008] and [0036] within Zhang et al.).
Combination of Zhang et al., Gao et al., and Fritz et al.
Regarding instant claim 21, Zhang et al., Gao et al., and Fritz et al. teach further comprising at least one additional layer, the at least one additional layer being distinct from the inner core and outer layer.
Zhang et al. and Gao et al. do not disclose further comprising at least one additional layer, the at least one additional layer being distinct from the inner core and outer layer. However, Fritz et al. disclose further comprising at least one additional layer, the at least one additional layer being distinct from the inner core and outer layer (further comprising a surface barium sulfate (additional layer) being distinct from the inner core and the outer coating; see paragraph [0075] within Fritz et al.).
It would have been obvious to one skilled in the art, prior to the effective filing date of the invention to have modified the embolic particle, as disclosed by Zhang et al. and Gao et al., to provide the embolic particle further comprising at least one additional layer, the at least one additional layer being distinct from the inner core and outer layer, as disclosed by Fritz et al., for the benefit that particles coated with an additional layer of barium sulfate provides enhance fluidization properties to the particles such that it reduces agglomeration especially during drying and coating thereby improving the overall coating and adhesion properties of the outer layer (see paragraph [0075] within Fritz et al.).
Combination of Koole and Reb et al.
Regarding instant claim 25, Koole and Reb et al. teach wherein the liquid includes saline.
Koole does not disclose wherein the liquid includes saline. However, Reb et al. disclose wherein the liquid includes saline (physiologically compatible solution (liquid) is saline; see column 23, lines 50-54; column 30, lines 43-54 within Reb et al.).
It would have been obvious to one skilled in the art, prior to the effective filing date of the invention to have modified the kit, as disclosed by Koole, to provide the kit wherein the liquid includes saline, as disclosed by Reb et al., for the benefit that microspheres are loaded with a therapeutic agent by adding the microspheres to the therapeutic agent in a physiological compatible solution (see column 29, lines 1-5; column 30, lines 43-54 within Reb et al.).
Combination of Koole and Vogel et al.
Regarding instant claim 27, Koole and Vogel et al. teach wherein the plurality of embolic particles remain the same size when the plurality of embolic particles are disposed in the liquid.
Koole does not disclose wherein the plurality of embolic particles remain the same size when the plurality of embolic particles are disposed in the liquid. However, Vogel et al. disclose wherein the plurality of embolic particles remain the same size when the plurality of embolic particles are disposed in the liquid (plurality of embolic particles are non-swellable (remain same size) when the plurality of embolic particles are disposed in a liquid; column 40, lines 11-16 within Vogel et al.).
It would have been obvious to one skilled in the art, prior to the effective filing date of the invention to have modified the kit, as disclosed by Koole, to provide the kit wherein the plurality of embolic particles remain the same size when the plurality of embolic particles are disposed in the liquid, as disclosed by Vogel et al., for the benefit of providing embolic microspheres (particles) with a size sufficient to embolize and release the therapeutic agent (see column 36, lines 16-33 and 61-67; and column 40, lines 11-16; both within Vogel et al.).
Combination of Zhang et al. and Gao et al.
Regarding instant claim 28, Zhang et al. and Gao et al. teach a method of manufacturing an embolic particle, the method comprising, providing an inner core having a volume within which a radioisotope can be accommodated, the inner core including a surface over which a layer can be arranged; providing a composition within which a therapeutic can be infused, and arranging the composition over the surface of the inner core to create an outer layer.
Zhang et al. disclose a method of manufacturing an embolic particle (method for preparing (manufacturing) embolic microspheres (small spherical particles); see paragraphs [0044]-[0045] within Zhang et al.), the method comprising, providing an inner core having a volume within which a radioisotope can be accommodated (providing an inner core having a volume within which a radionuclide (radioisotope) is accommodated; see Figure 1; see paragraphs [0008], [0010], and [0045] within Zhang et al.), the inner core including a surface over which a layer can be arranged (inner core has a surface over which a layer is arranged; see Figure 1, paragraphs [0008], [0010] within Zhang et al.); providing a composition within which a therapeutic can be infused (PLGA composition (composition within which a therapeutic can be infused as evidenced by Zhang that discloses a polymer shell accommodates a therapeutic; see paragraphs [0009], [0011], and [0044]); see Figure 1, paragraphs [0008] and [0010]; both within Zhang et al.), and arranging the composition over the surface of the inner core to create an outer layer (PLGA polymer shell being placed over the surface of the inner core; see Figure 1; paragraphs [0008], [0010], and [0045]; all within Zhang et al.).
Regarding instant claim 29, Zhang et al. and Gao et al. teach wherein the inner core includes a hollow inner chamber which can accommodate the radioisotope or the therapeutic.
Zhang et al. disclose wherein the inner core includes a hollow inner chamber which can accommodate the radioisotope or the therapeutic (microsphere with a core-shell structure has a cavity (inner core includes a hollow inner chamber) which can accommodate the radionuclide (radioisotope); paragraph [0027] within Zhang et al.).
Regarding instant claim 30, Zhang et al. and Gao et al. teach further comprising, infusing the radioisotope into the inner core.
Zhang et al. disclose further comprising, infusing the radioisotope into the inner core (inner core is embedded with a radionuclide (infusing); see abstract within Zhang et al.).
Regarding instant claim 31, Zhang et al. and Gao et al. teach further comprising, activating the radioisotope such that the embolic particle emits radiation.
Zhang et al. disclose further comprising, activating the radioisotope such that the embolic particle emits radiation (enabling the nuclide in the embolic microsphere (particle) to have radioactivity through neutron excitation; see paragraph [0016] within Zhang et al.).
Regarding instant claim 32, Zhang et al. and Gao et al. teach further comprising, infusing the outer layer with the therapeutic.
Zhang et al. does not disclose further comprising, infusing the outer layer with the therapeutic. However, Gao et al. disclose further comprising, infusing the outer layer with the therapeutic (therapeutic agent is added (infused) to the outer shell (layer); see paragraph [0074] within Gao et al.).
It would have been obvious to one skilled in the art, prior to the effective filing date of the invention to have modified the method, as disclosed by Zhang et al., to provide the method further comprising, infusing the outer layer with the therapeutic, as disclosed by Gao et al., for the benefit that radioactive particles with an inner core containing a radionuclide (radioisotope) and an outer shell (layer) containing a therapeutic are used to provide simultaneous radioactive and local drug treatment of malignant tumor cells (see paragraphs [0004], [0008], [0044], and [0080] within Gao et al.).
Regarding instant claim 33, Zhang et al. and Gao et al. teach wherein the therapeutic is premixed with the outer layer prior to the arranging step.
Zhang et al. does not disclose wherein the therapeutic is premixed with the outer layer prior to the arranging step. However, Gao et al. disclose the therapeutic is premixed with the outer layer prior to the arranging step (the therapeutic is added the raw material polycaprolactone of the outer layer (premixed) prior to the arranging step; paragraphs [0079]-[0080], and [0084] within Gao et al.).
It would have been obvious to one skilled in the art, prior to the effective filing date of the invention to have modified the method, as disclosed by Zhang et al., to provide the method wherein the therapeutic is premixed with the outer layer prior to the arranging step, as disclosed by Gao et al., for the benefit of preparing a biodegradable radioactive particle for the dual treatment effects of radiotherapy and drug treatment (see paragraph [0074] within Gao et al.).
Combination of Zhang et al., Gao et al., and Koole
Regarding instant claim 35, Zhang et al., Gao et al., and Koole teach further comprising activating radioisotopes within the inner core.
Koole does not disclose further comprising activating radioisotopes within the inner core. However, Zhang et al. disclose further comprising activating radioisotopes within the inner core [neutron excitation (activating)] radioactive nuclide (radioisotopes) in the inner core; paragraphs [0016] and [0036] within Zhang et al.).
It would have been obvious to one skilled in the art prior to the effective filing date of the invention to have modified the method, as disclosed by Koole, to provide the method further comprising activating radioisotopes within the inner core, as disclosed by Zhang et al. and Gao et al., for the benefit that radioactive embolic microspheres (small spherical particles) with radionuclide core are activated by neutron excitation to treat tumors (see paragraphs [0004] and [0016] within Zhang et al.).
Regarding instant claim 36, Zhang et al., Gao et al., and Koole teach further comprising irradiating the tumor cells at the site of interest.
Koole does not disclose further comprising irradiating the tumor cells at the site of interest. However, Zhang et al. disclose further comprising irradiating the tumor cells at the site of interest (radioactive nuclide release beta rays (irradiating) the tumor cells at the site of interest; see paragraphs [0004] and [0016] within Zhang et al.).
It would have been obvious to one skilled in the art prior to the effective filing date of the invention to have modified the method, as disclosed by Koole, to provide the method further comprising irradiating the tumor cells at the site of interest, as disclosed by Zhang et al. and Gao et al., for the benefit that radioactive embolic microspheres (small spherical particles) with radionuclide core are activated by neutron excitation to release radiation to treat tumors (see paragraphs [0004] and [0016] within Zhang et al.).
Regarding instant claim 41, Zhang et al., Gao et al., and Koole teach the method further comprising, treating at least one of primary or metastatic tumors of a liver, lungs, the brain or spinal cord, prostate, breast, esophagus, upper aerodigestive tract including the nasopharynx, nasal cavity, oral cavity, oropharynx, hypopharynx, larynx, neck, thyroid, lungs, mediastinum, stomach, small bowel, large bowel, pancreas, spine, kidneys, ureters, bladder, urethra, vagina, uterus, cervix, ovary, lymph nodes, muscles, and bones.
Koole further discloses the method further comprising, treating at least one of primary or metastatic tumors of a liver (treating primary liver cancer; paragraph [0069] within Koole).
Analogous Art
The Zhang et al., Gao et al., Koole, DiCarlo et al., Fritz et al., Reb et al., and Vogel et al. references are directed to the same field of endeavor as the instant claims, that is, an embolic particle for use in treatment of tumor cells, 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 embolic particle for use in treatment of tumor cells disclosed by Zhang et al., using the teachings of Gao et al., Koole, DiCarlo et al., Fritz et al., Reb et al., and Vogel et al. in order to arrive at the subject matter of the instant claims.
The Zhang et al., Gao et al., Koole, DiCarlo et al., Fritz et al., Reb et al., and Vogel et al. references all have considerable overlap in the embolic particle arts. In this instance, Zhang et al., Gao et al., and Koole supplies the template for the embolic particle, DiCarlo et al. and Fritz et al. supplies additional support for specific polymeric claim limitations, while Reb et al. and Vogel et al. supplies support for the liquid surrounding the embolic particles. All references are directed to the application of medical devices and therefore constitute analogous art under MPEP §2141.01(a). A POSITA would have reasonably consulted the seven references when seeking to develop an embolic particle for use in the treatment of tumor cells.
Given these teachings, a POSITA would have been motivated to combine the template for the embolic particles disclosed by Zhang et al., Gao et al., and Koole into the additional support for specific polymeric claim limitations disclosed by DiCarlo et al. and Fritz et al., and the support for the liquid surrounding the embolic particles taught by Reb et al. and Vogel et al.
The modification constitutes a simple substitution of one known element for another to obtain a predictable results [MPEP §2143(I)(B)].
The combination represents the use of a known technique to improve a similar device 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 embolic particle for use in treatment of tumor cells taught by Zhang et al. along with the use of the necessary claim limitations taught by Gao et al., Koole, DiCarlo et al., Fritz et al., Reb et al., and Vogel 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 Gao et al., Koole, DiCarlo et al., Fritz et al., Reb et al., and Vogel et al. would have been viewed by a POSITA as routine design optimizations or known modifications for embolic particles used in cancer treatment. The motivation to combine the seven references would be to create an embolic agent with a therapeutic drug that can be embedded within the outer biodegradable polymeric shell. Implementing these features in Zhang et al.’s embolic particles would not require more than ordinary skill or routine experimentation.
Accordingly, the combination of Zhang et al., supplemented by Gao et al., Koole, DiCarlo et al., Fritz et al., Reb et al., and Vogel et al. provides all the elements of the claimed invention. The resulting medical device for embolic particles for use in the treatment of tumor cells constitutes 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN W LIPPERT III whose telephone number is (571)270-0862. The examiner can normally be reached Monday - Thursday 9:00 AM - 5:00 PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert A Wax can be reached on 571-272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC)
at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JOHN W LIPPERT III/Examiner, Art Unit 1615
