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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on September 30, 2025 has been entered.
Applicants' arguments, filed September 30, 2025, have been fully considered but they are not deemed to be fully persuasive. The following rejections and/or objections constitute the complete set presently being applied to the instant application.
Based on the claim amendments, new prior art rejections are set forth below rendering the arguments set forth regarding the prior art rejections of record moot as none of the previously applied references are used in the new grounds of rejection set forth below.
Terminal Disclaimer
The terminal disclaimer filed on September 30, 2025 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of ant patent granted on Application No. 18/280,779 has been reviewed and is accepted. The terminal disclaimer has been recorded. Accordingly, the provisional non-statutory double patenting rejection based on this rejection has been withdrawn.
Claim Rejections - 35 USC § 112 – New Matter
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1 – 5, 8 and 21 – 26 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
Independent claims 1 and 21 have been amended with a negative proviso that the m second particle(s) are not embedded within said n first particle(s) and none of the cited locations provide support for this limitation. Any negative limitation or exclusionary proviso must have basis in the original disclosure. If alternative elements are positively recited in the specification, they may be explicitly excluded in the claims. See In re Johnson, 558 F.2d 1008, 1019, 194 USPQ 187, 196 (CCPA 1977) (“[the] specification, having described the whole, necessarily described the part remaining.”). See also Ex parte Grasselli, 231 USPQ 393 (Bd. App. 1983), aff’d mem., 738 F.2d 453 (Fed. Cir. 1984). The mere absence of a positive recitation is not basis for an exclusion. MPEP 2173.05(i). The only disclosure related to embedding is ¶ [0109] where the entirety to the nanobomb can be embedded in a substrate onto which cells can be cultured and not about the localization of the two different populations of particles in relation to one another in the nanobomb itself as in the negative proviso added to each independent claim.
All functional language regarding the n first particle(s) absorbing electromagnetic radiation to generate a vapor bubble that causes at least one m second particle(s) a certain distance away has been deleted from claim 1. Therefore the compositions encompassed by claim 1 and all claims that depend from claim 1 do not require those functions related to vapor bubble generation and leading to propulsion of at least one of the other population of particles a certain distance away. Claim 2 mentions a vapor bubble but does not require that the vapor bubble be generated by at least one of the n first particle(s) as in the disclosure as filed but does not require that the vapor bubble be generated by at least one of the n first particle(s) as previously. Independent claim 21 does not contain any such functional language and/or any requirement of vapor bubble generation and movement of at least one of the m second particle(s) upon vapor bubble generation. Claim 24 requires a configuration capable of vapor bubble generation under very specific conditions but does not require a vapor bubble to be generated and no link to propulsion of at least one m second particle when that would occur is set forth.
Each independent claim encompasses any combination of n first particle(s) and m second particle(s) made of a material as required by each claim for these particles but no other limitations are placed on the nanobomb composition. The word “nanobomb” is recited in each claim but the use of this word as part of the claimed composition does not impart additional limitations on the claimed composition such as the functional language that was previously present in claim 1. Therefore any combination of two populations of particles having the required material falls within the scope of the claims as based on Brownian motion, the limitation as to the proximity of at least one of the n first particle(s) and at least one of the m second particle(s) will be met.
A review of the disclosure as filed its entirety indicates that only specific combinations of particles were envisioned – namely compositions with one set of particles (the n first particle(s)) that absorb electromagnetic radiation and generate a vapor bubble and not all particles are capable of such a function. The other population of particles, the m second particle(s), are then propelled after that vapor bubble generation a distance D away. Not all populations of particles are capable of vapor bubble generation and with another population capable of being propelled a particular distance away after vapor bubble is generated. Therefore the current claim scope encompasses compositions that were not envisaged in the disclosure as originally filed. The Examiner was unable to locate any language in the disclosure as originally filed including the cited sections that the vapor bubble generation and particle propulsion with exemplary embodiments of the disclosed invention such that these functions were not required of all embodiments. Applicants are invited to explain along with specific quotes from the disclosure as originally filed to show implicit or inherent support for the claimed invention.
The dependent claims fall therewith.
Claim 24 was rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
While this claim was previously rejected as containing new matter and has been extensively amended to overcome the previous issue, claim 24 as currently written comprises new matter for the reasons set forth below.
The only reference in the disclosure as originally filed of 1 ns laser pulse with a fluence of 1 J/cm2 and a wavelength of 561 nm is in the description of Figure 2 (¶ [0155] of the PGPub of the instant application). That figure shows an iron oxide nanoparticle (IONP) as the first particle 2 that appears to have a size of 500 nm functionalized with streptavidin 5 and fluorescent polystyrene nanoparticles as the second particles 3 that are functionalized with biotin 4 to form the nanobomb 1. The conditions are stated as those in which the IONP “may generate a vapor bubble upon irradiation with a single laser pulse, for example, a 7 ns laser pulse with a fluence of 1 J/cm2 and a wavelength of 561 nm.” This specific recitation does not provide support for the language in amended claim 24 of the composition, as a whole, “is configured so that upon exposure of the composition to a single 7 ns laser pulse having a wavelength of 561 nm and a fluence of 1.05 J cm-2 the iron oxide nanoparticle generates a vapor bubble that propels the at least one of the polystyrene nanoparticles at least 0.01 µm away from the iron oxide nanoparticle”. Vapor bubble generation is described but that the particles are configured to do so and/or what features of the particles present are required to propel at least one the second polystyrene nanoparticles at least 0.01 µm away are not described. That the specific materials in Figure 2 can generate a vapor bubble when exposed to such laser light does not provide support for the full breadth of any compositions as encompassed by claim 24 that could generate a vapor bubble even if that was insufficient to move at least one polystyrene particle at least 0.01 µm away.
None of the cited sections provide sufficient support for using those specific conditions to generate vapor bubbles for the full scope of n first particle(s) as required by claim 24.
If Applicant is in disagreement with the Examiner regarding support for the amended claims, Applicant is respectfully requested to point to additional locations wherein support may be found for the instant invention and/or provide an explanation as to how implicit and/or inherent support is present for the claimed subject matter.
Claim Rejections - 35 USC § 112 – Written Description
Claim 24 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. this is a written description rejection.
Claim 24 has been amended to recite that the claimed n first particle(s) are configured so that upon exposure of the composition to a single 7 ns laser pulse having a wavelength of 561 nm and a fluence of 1.05 J cm-2 the iron oxide nanoparticle generates a vapor bubble that propels the at least one of the polystyrene nanoparticles at least 0.01 µm away from the iron oxide nanoparticle”. The features and/or structures that result in iron oxide particles that are capable of generation a vapor bubble under these very specific conditions are not set forth in the disclosure as originally filed. A description that merely renders a claimed invention obvious may not sufficiently describe the invention for the purposes of the written description requirement of 35 U.S.C. 112 (MPEP 2163 (I)). Without a description of the structure(s) or structural features (e.g., size or the presence of a coating material) that are linked to the required function of vapor bubble generation under the specific conditions recited in this claim, the written description requirement has not been fully satisfied for claim 24.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1, 2 and 5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Townley et al. (WO 2016/166550).
Townley et al. discloses an embolization microparticle coated with a plurality of nanoparticles comprising titanium dioxide, zinc oxide or cerium dioxide doped with one or more rare earth elements (whole document, e.g., abstract and Figure 10). The microparticle reads on the m second particles(s) of the instant claims while the metal oxide nanoparticles read on the n first particle(s) of the instant claims and neither type of particle is embedded in the other type of particle. Given the association in the final structure with contact between the two populations of particles, at least one of m second particle(s) must be functionalized with one or more functional group to induce a linking strategy with the at least one of said n first particle(s). Polystyrene divinylbenzene microparticles were coated with gadolinium doped titania nanoparticles on p 30, ¶ 3.
As to claim 2, there is no evidence of record that the microparticles is not adapted to alter a biological barrier if propelled by a vapor bubble. “As a practical matter, the Patent Office is not equipped to manufacture products by the myriad of processes put before it and then obtain prior art products and make physical comparisons therewith.” MPEP 2113 It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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 nonobviousness.
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.
Claim(s) 1 – 5 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Townley et al. (WO 2016/166550).
Townley et al. discloses an embolization microparticle coated with a plurality of nanoparticles comprising titanium dioxide, zinc oxide or cerium dioxide doped with one or more rare earth elements (whole document, e.g., abstract and Figure 10). The microparticle reads on the m second particles(s) of the instant claims while the metal oxide nanoparticles read on the n first particle(s) of the instant claims and neither type of particle is embedded in the other type of particle. The multimodal particles treat cancer by simultaneously embolizing tumor vasculature and radiotherapeutically treating the tumor (p 3, ¶ 3). Typically the microparticle forms the core of the particle with the nanoparticles typically forming a coating or outer layer on the core and the nanoparticles typically adhere directly to the surface of the nanoparticle (p 5, ¶ 5) although the microparticle may additionally comprise some of the nanoparticles or other different nanoparticles (p 5, ¶ 6). The embolization particle can be in size range of 5 – 100 µm or 5 – 50 µm (p 6, ¶ 1). The particle size distribution may be varied to correspond closely to the vascular diameter in various tumors and therefore to more effectively occlude vasculature within the tumor (¶ bridging p 17 and 18). The diameter of tumor vasculatures is reported in Table 1 on p 18. The microparticle can be 0.1 – 500 µm in size and preferably 10 – 200 µm and can be used for embolization alone (p 13, ¶ 3). The microparticle is typically an inert material and polymer, metal and inorganic compound are taught as suitable (p 13, ¶ 5). Examples of suitable polymers include polystyrene (p 14, ¶ 2) and preferably the microparticle comprises a polymer or copolymer formed from styrene monomer units (p 14, ¶ 6). Various strategies to coat the microparticle with nanoparticles were tried with electrostatic binding of the titania nanoparticles vis the positively charged electrolyte PDADMAC (p 40, ¶ 2) and sintering (p 40, ¶ 3) were used to coated the nanoparticles onto the microparticle. The nanoparticles typically have an average diameter of less than 200 nm (p 9, ¶ 4) and more preferably 5 – 75 nm (p 10, ¶ 1). At least one targeting moieties such as lipids can also be present on the nanoparticles (p 17, ¶ 2). Additional modalities such as imaging agents such as fluorophores or heavy metals, radiopaque nanoparticles or chemotherapeutic agents can be present in the embolization particles (p 15, ¶ 4 onward).
An example with a targeting ligand or a property as in claim 4 is not specifically disclosed.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to prepare polystyrene containing embolization particles with nanoparticles having a targeting ligand such as a lipid on them coated onto the microparticle. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because the nanoparticles need to be coated onto the microparticles and not embedded. Based on the teachings of Townley et al. as to possible coating methods, the coating process depends on the materials being used to prepare the embolization particles can be accomplished by functionalizing the surface of the microparticle. The size of embolization particle overall and the size of the microparticle and nanoparticle in the embolization particle are results effective parameters that one of ordinary skill in the art would routinely optimize. The size ranges overlap or just touch those that are claimed which are prima facie obvious absence evidence of record as to the criticality of the claimed range (see MPEP 2144.05). Smaller embolization particles will allow for the embolization of smaller blood vessels in tumors, which as shown in Table 1 can be less than 10 µm in diameter. One of ordinary skill in the art would also optimize the number of embolization particles without a nanoparticle coating in the composition that are still suitable to embolize vasculature. Particles coated with nanoparticles will have additional functionality but treat the cancer by different mechanisms as taught by Townley. Un-coated microparticles can be added to the composition to provide sufficient embolization while still providing a suitable dose of radiotherapeutic agent that is sufficient but not excessive as too high of doses of radiotherapeutic agent can cause more or more severe side effects upon administration.
Claim(s) 1 – 5, 8 and 21 – 26 are rejected under 35 U.S.C. 103 as being unpatentable over Townley et al. as applied to claims 1 – 5 and 8 above, and further in view of Vogel et al. (WO 01/72281).
Townley et al. is discussed above,
The presence of iron oxide nanoparticles is not disclosed.
Vogel et al. discloses 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 (whole document, e.g. abstract) that can be used to treat diseases such as cancer that comprise bioactive therapeutic factors in association with microspheres as carriers (p 1, ¶ 1). A polymeric material can be the carrier (¶ bridging p 6 and 7). Physical linkages can be used to physically linked them to one another (p 6, ¶ 4) with adsorption by means such as ion exchange, hydrophobicity, molecular recognition or combinations thereof being disclosed on p 7, ¶ 6. The materials can be used in connection with diagnostic imaging so contrast agents may serve to increase the effectiveness of the bioactive therapeutic factor transfection agent microspheres composition of the present invention as contrast agents (p 55, ¶ 2). Iron oxide and magnetic iron oxide are exemplified as superparamagnetic contrast agents suitable for use with the disclosed invention although other metal oxides are also superparamagnetic contrast agents (p 57, ¶ 2). These agents are nano- or microspheres and iron oxide particles about 3 nm to about 5 nm have probably the most balanced relaxation rates although the particles 100 nm in diameter would still be considered nanoparticles (p 58, ¶ 1). The iron oxides can be adsorbed onto the surface, incorporated into the wall of the microsphere or entrapped within the interior (p 58, ¶ 2).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to iron oxide particles such as superparamagnetic iron oxide nanoparticles onto the surface of the embolization particles of Townley et al. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because Vogel et al. discloses that contrast agents such as iron oxide nanoparticles can be used as contrast agents in polymeric embolization particles. Townley et al. generally discloses the presence of additional modality of imaging can be added but not iron oxide particles specifically. Contrast agents allow for imaging via different modalities or improved image contrast and Vogel et al. discloses that iron oxide nanoparticles can be added for contrast purposes when images are taken in combination with embolization particles. Note that while the art references microparticles and claim 21 requires nanoparticles, given the size range recited in instant claim 25, particles up to 10 µm in diameter fall within the scope of nanoparticles.
As to claims 24, there is no evidence of record that the composition rendered obvious by Townley et al. and Vogel et al. is not configured in the required manner. There is also no evidence of record that the density requirement of claim 25 is not met. “As a practical matter, the Patent Office is not equipped to manufacture products by the myriad of processes put before it and then obtain prior art products and make physical comparisons therewith.” MPEP 2113 It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Nissa M Westerberg whose telephone number is (571)270-3532. The examiner can normally be reached M - F 8 am - 4 pm.
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/Nissa M Westerberg/Primary Examiner, Art Unit 1618