DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant's election with traverse of Group II, now including claims 15-18, 21-31, 35-37, and 39-44, in the reply filed on 05/22/2026 is acknowledged. The traversal is on the grounds that Krishna does not explicitly state that the photonic nanoparticles are at or delivered to a kidney stone and therefore the combination of photonic nanoparticles with kidney stones possesses a special feature compared to Krishna. This is not found persuasive in view of the references below, which anticipate and make obvious the use of photonic nanoparticles for treating kidney stones.
The requirement is still deemed proper and is therefore made FINAL.
As such, claims 1-2, 6-9, 11-12, 14, and 38 are withdrawn from further consideration as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Status of Claims
Receipt of Remarks/Amendments filed on 05/22/2026 is acknowledged. Claims 18 and 31 are amended and claims 3-5, 10, 13, 19-20, and 32-34 are canceled. Claims 39-44 are new. As discussed above claims 1-2, 6-9, 11-12, 14, and 38 are withdrawn. Claims 15-18, 21-31, 35-37, and 39-44 are examined on the merits herein.
Priority
The instant application filed 12/04/2023, is a 371 filing of PCT/US2022/032336, filed 06/06/2022, which claims priority to Provisional Application No. 63/196,938, filed 06/04/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/04/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 15-18, 21-31, 35-37, and 39-44 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The term “vicinity” in claims 15, 18, and 36 is a relative term which renders the claim indefinite. The term “vicinity” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. For the sake of compact prosecution vicinity is being interpreted as any surrounding area of a kidney stone.
The term “substantially” in claim 26 is a relative term which renders the claim indefinite. The term “substantially” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. For the sake of compact prosecution substantially is being interpreted as an degree of transparency.
Claims 30 and 44 recite wherein said nanoparticles are irradiated from a distance of more than 3 mm or 5 mm, respectively. Such a range is one sided and includes infinite distance, thereby rendering the claim unclear. Furthermore, it is unlikely that the nanoparticles can be irradiated from longer distances which are currently included in the instant range.
Claims 31 recites “PHF” without defining the abbreviation, thereby rendering the claim unclear. For the sake of compact prosecution PHF is interpreted as polyhydroxyfullerene.
Claim 41, which depends on claim 15, recites the limitation "the ligand". There is insufficient antecedent basis for this limitation in the claim since claim 15 does not define a ligand.
The remaining claims are rejected by virtue of their dependency on claim 15.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 15-17, 26-27, 29, 37, and 43 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Kislev et al. (US 20080045865 A1, 02/21/2008, PTO-892), hereinafter Kislev.
Kislev discloses a method for localized delivery of heat useful for localized imaging and treatment of a biological material (abstract).
Regarding claim 15: The method for inducing localized delivery of heat to a cell or a tissue comprises: a. administering (i.e., delivering) a plurality of nanoparticles to the cell or tissue; and b. irradiating the nanoparticles administered to said cell or tissue by electromagnetic radiation ([0042]-[[0044]; claim 20). The nanoparticles display enhanced absorption of electromagnetic radiation ([0028]), and the electromagnetic radiation used to irradiate said nanoparticles is ultraviolet, visible or infrared radiation ([0036]; claim 103). As such, the nanoparticles of Kislev read on photonic nanoparticles and the electromagnetic radiation reads on non-ionizing electromagnetic radiation. In one embodiment, the method above is for reducing the size of or removing at least one stone from a kidney (claim 52), for example, to break (i.e., fragment) kidney stones ([0055]). Such a use inherently requires the nanoparticles to be delivered in a vicinity of the kidney stone within a patient.
Regarding claim 16: While it is not explicitly taught by Kislev that the nanoparticles yield acoustic energy in response to being irradiated, such a property is believed to be inherent to photonic nanoparticles. Additionally, it is considered inherent that when these nanoparticles are used to treat kidney stones that they would perform work on said kidney stones to cause the reduction in size or fragmentation taught by Kislev. Because the photonic nanoparticles of Kislev are identical to those defined in claims 15 and 16, the nanoparticles must necessarily have the characteristics claimed as an inherent property. 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 to be shown in the prior art does not possess the characteristic relied on” (205 USPQ 594). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference.
Regarding claim 17: Most of the energy due to optical absorption (in the nanoparticles) is converted into heat. Thus, resonant illumination of highly absorptive nanoparticles can provide significant local heating to the microscopic environment of the nanoparticles ([0101]). When an absorbing particle is exposed to a continuous electromagnetic radiation, the absorbed power is transferred to the surrounding tissue thereby increasing the tissue temperature ([0139]), which reads on thermal energy being delivered to the treatment area (i.e., kidney stone) in response to the nanoparticles being irradiated.
Regarding claim 26: The nanoparticles are exposed to optical pulsed radiation. Specifically, the optical radiation may be delivered to a subject through the skin surface ([0186]). Fig. 2 shows a target tissue 1, to which the nanoparticles have been administered, and electromagnetic beam 12 illuminating the target tissue 1 through the patient skin 14 ([0176]), thereby reading on irradiation of nanoparticles at a wavelength at which human soft tissues are substantially transparent to. The electromagnetic radiation used to irradiate the nanoparticles is infrared radiation ([0036]; [0180]; [0217]; claims 103-104).
Regarding claim 27: The electromagnetic radiation used to irradiate the nanoparticles is infrared radiation in the ranges of from about 800 to 1300 nm. ([0036]; claim 104). A wavelength of 800 nm falls within the claimed range of 700-950 nm, while a wavelength of 1300 nm falls within the claimed range of 1000-1350 nm. The electromagnetic radiation source is selected from various lasers ([0034]; [0037]; claim 79).
Regarding claim 29: It can be seen in Fig. 2, and is discussed above in regards to instant claim 26, that the electromagnetic source 8 delivers an electromagnetic beam 12 which illuminates the target tissue 1 through the patient skin 14 ([0176]). It is also taught that the electromagnetic radiation source is selected from various lasers ([0034]; [0037]; claim 79). Thus, it is inherently taught that the irradiation of the nanoparticles is achieved via a laser emitter which is not physically contacting the target (i.e., the kidney stone) since the electromagnetic beam is delivered through the skin.
Regarding claim 37: Kislev does not disclose the placement of a ureteral stent, as such, the method inherently excludes this step.
Regarding claim 43: The electromagnetic radiation absorbing nanoparticles may include gold. Gold nanoparticles are commonly used in biological and biomedical applications, specifically gold nanoshells ([0100]-[0102]). Specifically, a gold nanoshell dispersion is prepared for the invention ([0106]).
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.
1. Claims 15-18, 22, 26-27, 29-30, 35, 37, and 43-44 are rejected under 35 U.S.C. 103 as being unpatentable over Kislev et al. (US 20080045865 A1, 02/21/2008, PTO-892), hereinafter Kislev..
The teachings of Kislev are disclosed above as are the rejections of 15-17, 26-27, 29, 37, and 43.
Kislev further teaches that the nanoparticles may be administered to the cell or tissue using targeting schemes involving specific chemical interactions or may consist of the simple delivery of the nanoparticles to the desired area, preferably by the delivery of a pharmaceutical composition comprising the nanoparticles according to the present invention ([0108]). Conjugating targeting materials to nanoparticles increases their tendency to stick onto targeted cells or tissue or even non- cell non-tissue materials like kidney stones ([0012]). According to one embodiment, the administered nanoparticles are targeted to the desired location by the use of appropriate chemical schemes, including ligand-receptor complexes ([0051]; claims 98-99). The pharmaceutical composition comprising the nanoparticles is formulated for parenteral administration, e.g., formulated for injection via the intravenous route ([0111]). The cell or tissues to which the nanoparticles are delivered include that of the kidney ([0134]-[0136]).
The teachings of Kislev differ from that of the instantly claimed invention in that Kislev does not explicitly teach a specific embodiment utilizing the delivery method of claim 18, the irradiation distance of claims 30 and 44, nor a specific embodiment wherein the nanoparticles are in contact with the kidney stone as defined in claims 22 or functionalized according to claim 35.
Regarding claim 18, 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 administer the nanoparticles of Kislev intravenously in the vicinity of the kidney stone within the kidney since intravenous administration and administration to the kidney are both known and routine in the art as taught by Kislev. One of ordinary skill in the art could have applied the known technique of intravenous administration to the known method of nanoparticle administration to predictably yield the instant method. It would have also been obvious to deliver said nanoparticles to the kidney since it is an exemplary target tissue/cell taught by Kislev, which one of ordinary skill in the art would have been motivated to target in the case of treating kidney stones. Furthermore, the method of reducing the size of or removing at least one stone from a kidney, as taught by Kislev, inherently requires the nanoparticles to be delivered in a vicinity of the kidney stone within the kidney.
Regarding claims 22 and 35: 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 conjugate targeting materials (i.e., a ligand) to the nanoparticles of Kislev in order to bring nanoparticles in contact with the kidney stones prior to activation, since such a method is known and routine in the art as taught by Kislev. One of ordinary skill in the art would have been motivated to conjugate a targeting material onto the nanoparticles in order to being them in contact with the kidney stones being treated since the closer the nanoparticles are to the target prior to activation, the more localized the delivery of heat will be. Increasing localization increases the desired therapeutic effect while reducing undesired off target effects, as recognized by one of ordinary skill in the art. The conjugation of a targeting material to the nanoparticles also reads on the nanoparticles being functionalized with a ligand that interacts with a predetermined kidney-stone composition as recited in claim 35. Kislev teaches that such conjugation increases the tendency of the nanoparticles to stick onto targeted kidney stones, thereby reading on interactions which produce adhesion.
Regarding claims 30 and 44: As discussed above, Figure 2 illustrates a target tissue 1, to which the nanoparticles have been administered, and electromagnetic beam 12 illuminating the target tissue 1 through the patient skin 14 (Fig. 2; [0176]). While not explicitly defined, there is an inherent distance that exists between the point of irradiation and the nanoparticles in the target tissue. It is well within the abilities of an ordinary artisan to optimize the irradiation distance in the method depending on the desired strength of irradiation and location of the target tissue. As such, one of ordinary skill in the art would have arrived at the instantly claimed range of more than 3 mm or more than 5 mm through no more than routine experimentation. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
One of ordinary skill in the art would have had a reasonable expectation of success in making the above modifications since all of these modifications are either encouraged or optimizable from the teachings of Kislev.
Claims 15-18, 21-22, 26-27, 29-30, 35, 37, and 43-44 are rejected under 35 U.S.C. 103 as being unpatentable over Kislev as applied to claims 15-18, 22, 26-27, 29-30, 35, 37, and 43-44 above, and further in view of Shock wave lithotripsy (SWL) by Boston Scientific. (2016). (PTO-892), hereinafter Boston Scientific.
The teachings of Kislev are discussed above.
The teachings of Kislev differ from that of the instant invention in that Kislev does not explicitly teach the kidney stone being within the ureter as recited n claim 21.
Boston Scientific teaches that shock wave lithotripsy is recommended if you have medium-sized stones in your kidney or ureter (p. 1, para. 1). Such a procedure targets the stone with high-energy shock waves from outside the body. The goal of the procedure is to break the stone into small fragments that can pass in the urine over the next few weeks (p. 1, para. 2).
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 perform the method of Kislev on a kidney stone in the ureter of the patient since treatment of kidney stones in the ureter is known and routine in the art as taught by Boston Scientific. Both Kislev and Boston Scientific teach methods of reducing the size or fragmenting kidney stones, specifically through the delivery of an external stimuli to a target site. One of ordinary skill in the art could have therefore applied the known technique of Kislev to a kidney stone in the ureter since this is known and routine location to treat kidney stones with similar methods, as taught by Boston Scientific. One of ordinary skill in the art would have had a reasonable expectation of success in using the method of Kislev to treat a kidney stone in the ureter since Boston Scientific teaches that similar methods can be used to treat kidney stones in both the kidney and the ureter.
Claims 15-18, 22-24, 26-27, 29-30, 35-37, and 43-44 are rejected under 35 U.S.C. 103 as being unpatentable over Kislev as applied to claims 15-18, 22, 26-27, 29-30, 35, 37, and 43-44 above, and further in view of DiVito et al. (US 20170027647 A1, 02/02/2017, IDS dated 12/04/2023), hereinafter DiVito.
The teachings of Kislev are discussed above.
Kislev further teaches that the nanoparticles are administered to the cell or tissue by the delivery of a pharmaceutical composition comprising the nanoparticles ([0108]). Various types of pharmaceutical compositions may be used depending on the desired form of administration ([0109]). Aqueous compositions comprise an effective amount of nanoparticles dissolved and/or dispersed in a pharmaceutically acceptable carrier and/or aqueous medium. "Pharmaceutically and/or pharmacologically acceptable" refer to molecular entities and/or compositions that do not produce an adverse, allergic and/or other deleterious effects when administered to an animal (i.e., biocompatible). The use of pharmaceutically acceptable carriers is well known in the art ([0110]). The electromagnetic source of Kislev may be selected from a solid state laser, diode laser, or a gaseous laser ([0034]; [0037]; claim 79).
The teachings of Kislev differ from that of the instant invention in that Kislev does not explicitly teach the irradiation being delivered retrograde at the power output of claims 23 and 24, nor a gel as recited in claim 36.
DiVito discloses the use of a laser light and other energy sources in the field of dentistry, medicine and veterinary medicine to perform endodontic, periodontic, and other dental and medical procedures ([0003]). The method for treating a treatment zone comprises the steps of (A) providing a laser system containing a source of a laser light beam and an elongate optical fiber connected to said source and configured to transmit said laser light beam to a tip thereof, (B) immersing at least a portion of a tip of a light beam producing apparatus into a fluid reservoir located in the treatment pocket, the fluid reservoir holding a first fluid; and (C) pulsing the laser light source at a first setting, wherein at least a substantial portion of any contaminants located in or adjacent the treatment pocket are destroyed or otherwise disintegrated into fragmented material ([0015]). Additional medical uses for the photoacoustics of DiVito include breaking up kidney stones and other blockages in the body. In such a use, a flexible fiber optic could be fished up the urethra and placed adjacent to the stone (Table 2, p. 17-18 bridging entry). Such a method reads on delivering irradiation retrograde via a laser, as recited in claims 23 and 24. In a preferred embodiment, the laser source is a solid state laser having a wavelength of from about 700 nm to about 3000 nm, such as NdYAG, ErYAG, HoYag, NdYLF, Ti Sapphire, or ErCrYSGG laser ([0039]), which reads on the infrared wavelength of claims 23 and 24. The pulsing laser induces oscillating photoacoustic energy waves which emanate from the applicator tip into adjacent fluid medium from a light energy source maintained at a relatively low power setting of from about 0.1 to no more than about 1.5 watts or from about 0.4 watts to about 4.0 watts ([0036]). All of these wattages fall within the range of claim 23, with the examples of 0.1 and 0.4 watts falling within the range of claim 24. The first solution of DiVito preferably includes a compound containing molecules with at least one hydroxyl functional group and/or other excitable functional groups which are susceptible to excitation by a laser or other energy source. Solutions containing fluids other than water may be used, such as gels. The solution may also include dispersions or mixtures of particles containing nano- or micro-structures, preferably in the nature of fullerenes, such as nanotubes or bucky balls, or other nanodevices (including micro-sized devices) capable of sensitizing or co-acting with oxygenating, energizable, or activatable components in the solution/mixture ([0038]). As such, DiVito teaches gel solutions which may comprise nanoparticles dispersed within, thereby reading on the biocompatible gel of claim 36.
Regarding claims 23 and 24, 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 deliver the irradiation in the method of Kislev using the retrograde method and laser of DiVito since such a method is known and routine in the art as taught by DiVito. Both Kislev and DiVito teach the treatment of kidney stones by delivering infrared radiation to the treatment area. One of ordinary skill in the art could have used the known retrograde technique of DiVito (i.e., fishing a flexible laser up the urethra and placing near the stone) to improve the similar method of Kislev, which also applies electromagnetic radiation to a treatment area, specifically kidney stones. The retrograde technique of DiVito has the benefit of getting closer to the kidney stone than the transcutaneous method generally taught by DiVito, which one of ordinary skill in the art would recognize as having the advantage of reaching more internal areas on the body and providing improved radiation at a lower power. Both Kislev and DiVito teach lasers operating an infrared wavelength.
Regarding the power output of claims 23 and 24, DiVito specifically teaches a power output in such methods to be 0.1-1.5 watts or 0.4-4.0 watts. It would have therefore been prima facie obvious to one of ordinary skill in the art to use any of these power outputs when using the retrograde irradiation method of DiVito since these are known and effective wattages to use with the irradiation method of DiVito. Additionally, power level is a results effective parameter that one of ordinary skill in the art would have been motivated to optimize depending on the desired radiation. The optimization of a result effective parameter is considered within the skill of the artisan. See, In re Boesch and Slaney (CCPA) 204 USPQ 215. This is what research chemists do, optimization of result-effective variables through routine experimentation (MPEP 2144.05 IIA and B).
Regarding claim 36, it would have been prima facie obvious to one of ordinary skill in the art to formulate the nanoparticles of Kislev in a gel since this is a known and routine carrier in the art as taught by DiVito. As discussed above, Kislev teaches biocompatible solutions having nanoparticles dispersed in any pharmaceutically acceptable carrier known in the art. DiVito teaches that gels are known and routine carriers for dispersing activatable nanoparticles. As such, one of ordinary skill in the art could have combined the nanoparticles of Kislev with the gel dispersion/suspension taught by DiVito to predictably yield the instant invention. Both Kislev and DiVito teach such solutions as being delivered to a target site and undergoing radiation. As such, it would have been further obvious to deliver such a nanoparticle gel in the vicinity of a kidney stone, as taught by Kislev, wherein the solution partially coats the kidney stone, thereby improving the localization of heat release upon irradiation to the targeted kidney stone.
One of ordinary skill in the art would have had a reasonable expectation of success in making the above modifications since Kislev and DiVito both teach infrared radiation to a target site to which a solution of activatable nanoparticles has been delivered, specifically in the context of fragmenting kidney stones. Additionally, Kislev welcomes the use of solid state infrared lasers such as those taught by DiVito.
Claims 15-18, 22, 25-31, 35, 37, and 43-44 are rejected under 35 U.S.C. 103 as being unpatentable over Kislev as applied to claims 15-18, 22, 26-27, 29-30, 35, 37, and 43-44 above, and further in view of Krishna et al. (2010). Polyhydroxy Fullerenes for Non-Invasive Cancer Imaging and Therapy. Small, 6: 2236-2241 (on record, supplemental provided in 892), hereinafter Krishna, as evidenced by B&W Tek, Inc. (2014). BFW2 Laser System. (PTO-892), hereinafter B&W Tek.
The teachings of Kislev are discussed above.
Kislev further teaches that the electromagnetic radiation absorbing nanoparticles can be made from non-metallic materials, for example carbon ([0048]; [0100]; claim 93). The electromagnetic source may be selected from a solid state laser, diode laser, or a gaseous laser ([0034]; [0037]; claim 79).
The teachings of Kislev differ from that of the instantly claimed invention in that Kislev does not explicitly teach the power output and specific laser of claims 25 and 28, nor the nanoparticles of claim 31.
Krishna discloses polyhydroxy fullerenes (PHF) for non-invasive cancer imaging and therapy (title). In vivo photothermal ablation experiments conducted by intratumoral injection of CP-0.25 nanoparticles (i.e., chitosan encapsulated PHF) are disclosed. Starting immediately after injection, the mouse tumor was irradiated with 500 mW, 785 nm continuous-wave near infrared laser for 10 minutes. Two hours later, the tumors were smaller in cross-sectional area by an average of 32% (p. 2238-2239, bridge paragraph). Such a method reads on irradiating photonic nanoparticles via a laser operating at an infrared wavelength and at less than 5 W, as defined in claim 25. It can be seen in figure 4a that the laser delivers the irradiation through the skin (i.e., transcutaneously), which further reads on claim 25. The above method also reads on irradiation of nanoparticles via an external laser emitter generating infrared radiation energy at not more than 5 W, as recited in claim 28. The supplemental information of Krishna further teaches that the photothermal tumor treatment method utilizes a continuous wave laser (B&W TEK Inc, BWF2-785-5-400-0.22-SMA) (p. 4-5, bridge paragraph of Suppl.). The BWF2 laser is a fiber-coupled laser diode containing a thermoelectric cooler with internal fan, as evidenced by B&W TEK, meaning it omits a liquid cooling circuit as defined in claim 28. While the dB range is not defined by the art, the instant specification also utilizes a near-infrared laser (785 nm) by B&W Tek, which is believed to be the same as that disclosed by Krishna. As such, it is believed that the laser of Krishna inherently operates at less than 30 dB as recited in claim 28. Overall, Krishna teaches that photoacoustic and photo-thermal properties of polyhydroxy fullerenes can be exploited for non-invasive imaging and treatment of cancer (p. 2239, right col., para. 2). The PHF fullerenes of Krishna further read on the photonic nanoparticles of claim 31, which yield thermal and acoustic energy in response to being irradiated. Use of polyhydroxy fullerenes for cancer theranostics has several advantages over currently proposed single-wall carbon nanotubes and gold based nanostructures. PHF is water-soluble, biocompatible and biodegradable, and has been shown to possess antioxidant properties, inhibit allergic response and protect tissues of the central nervous system. PHF molecules are 1.3 nm in size and can be easily excreted in urine, whereas larger nanostructures such as carbon nanotubes and gold-based nanostructures typically exceed the renal excretion limit of 5.5 nm (p. 2240, left col., para. 3).
Regarding claim 25, it would have been prima facie obvious to one of ordinary skill in the art to perform the irradiation step of Kislev with a laser operating at 500 mW since it is a known and routine power to transcutaneously irradiate photonic nanoparticles in the art as taught by Krishna. Both Kislev and Krishna teach irradiating photonic nanoparticles transcutaneously via a laser at an infrared wavelength. Since 500 mW is an known and effective power at which to irradiate photonic nanoparticles through the skin, one of ordinary skill in the art could have used the known power of 500 mW in the similar method of Kislev to predictably yield the instantly claimed invention. Furthermore, power output is a results effective parameter that one of ordinary skill in the art would have been motivated to optimize. The optimization of a result effective parameter is considered within the skill of the artisan. See, In re Boesch and Slaney (CCPA) 204 USPQ 215. This is what research chemists do, optimization of result-effective variables through routine experimentation (MPEP 2144.05 IIA and B).
Regarding claim 28, both Kislev and Krishna teach irradiation of nanoparticles via an external laser emitter generating infrared radiation energy. Krishna makes obvious a power of 500 mW, as discussed above, which reads on less than 5 W. It would have been further prima facie obvious to utilize the BW Tek BFW2 laser of Krishna as the external laser emitter in the combined method, since such a laser is known and routine in the art as taught by Krishna. One of ordinary skill in the art could have used the laser of Krishna as the infrared laser in the combined method since it is known and effective for transcutaneously delivering infrared radiation to photonic nanoparticles, such as the method of Kislev. Thus, one of ordinary skill in the art could have replaced the infrared laser emitter of Kislev with the known infrared laser emitter of Krishna to predictably yield the instant invention. As discussed above, the laser of Krishna possesses the instantly claimed technical elements. Even in a case where the laser of Krishna does not operate at less than 30 dB, it would have been prima facie obvious to one of ordinary skill in the art to select a laser which does, as motivated by the elimination of noise.
Regarding claim 31, 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 use the polyhydroxy fullerene nanoparticles (PHF) of Krishna, in the method of Kislev since PHF nanoparticles are known and routine photonic nanoparticles in the art as taught by Krishna. Both Kislev and Krishna teach electromagnetic radiation absorbing nanoparticles that are delivered to a target and activated with infrared light causing the nanoparticles to release heat. One of ordinary skill in the art could have replaced the electromagnetic radiation absorbing nanoparticles of Kislev with the PHF nanoparticles of Krishna through no more than simple substitution of one known element for another to predictably yield the instantly claimed invention. One of ordinary skill in the art would have been motivated to use the PHF nanoparticles of Krishna over other known nanoparticles taught by Kislev, such as carbon nanotubes and gold based nanostructures, since PHF is water-soluble, biocompatible and biodegradable, and has been shown to possess antioxidant properties, inhibit allergic response and protect tissues of the central nervous system as well as being easily excreted in urine. The PHF nanoparticles of Krishna further read on the nanoparticles of claims 16-17 and 43.
One of ordinary skill in the art would have had a reasonable expectation of success in making the above modifications since 1) the nanoparticles of Kislev and Krishna operate by similar mechanisms and Kislev welcomes nanoparticles made of carbon and 2) the lasers of Kislev and Krishna are used in similar methods for the same purpose and Kislev welcomes diode lasers.
Claims 15-18, 22, 26-27, 29-30, 35, 37, 39-41, and 43-44 are rejected under 35 U.S.C. 103 as being unpatentable over Kislev as applied to claims 15-18, 22, 26-27, 29-30, 35, 37, and 43-44 above, and further in view of Cole et al. (2016). Targeted delivery to bone and mineral deposits using bisphosphonate ligands, Advanced Drug Delivery Reviews, Volume 99, Part A, Pages 12-27 (PTO-829), hereinafter Cole.
The teachings of Kislev are discussed above.
As discussed above, Kislev teaches that the nanoparticles may be administered to the cell or tissue using targeting schemes involving specific chemical interactions ([0108]). Conjugating targeting materials to nanoparticles increases their tendency to stick onto targeted cells or tissue or even non- cell non-tissue materials like kidney stones ([0012]). According to one embodiment, the administered nanoparticles are targeted to the desired location by the use of appropriate chemical schemes, including ligand-receptor complexes ([0051]; claims 98-99).
The teachings of Kislev differ from that of the instant invention in that Kislev does not explicitly teach the ligands of claims 39-41.
Cole discloses targeted delivery to bone and mineral deposits using bisphosphonate ligands (title). Targeted delivery enables accumulation of a high local dose of a therapeutic or imaging contrast agent to diseased bone or pathological calcifications (abstract). Bone pathologies and pathological calcifications in soft tissues can be diagnosed and treated by targeted delivery of imaging probes and pharmaceuticals to these mineral sites. Pathological calcifications are deposits of mineral in soft tissues, such as kidney stones (Intro, para. 1). Bisphosphonates can be conjugated to nanoparticles for targeting mineral in bone and pathological calcifications for drug delivery, diagnostic imaging, and radiotherapy (Fig. 1). The bisphosphonate of Cole reads on the ligand of claims 39 and 41. Many other molecules besides BPs also exhibit bone-targeting characteristics. Many noncollagenous proteins that are found in bone exhibit binding affinity to hydroxyapatite due to repeating amino acids such as glutamic or aspartic acid. These amino acids exhibit a negative charge due to carboxylate ligands, which chelate calcium ions on the surface of hydroxyapatite (Section 3.3, para. 1). Such amino acids read on the ligand of claims 40 and 41.
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 conjugate the bisphosphonates or carboxylate containing amino acid ligands taught by Cole to the nanoparticles of Kislev, since such ligands are known and routine in the art for targeting mineral calcifications such as kidney stones. Kislev teaches wherein the nanoparticles are coupled to at least one type of molecule that specifically binds to a target, particularly in the context of kidney stones. As such, one of ordinary skill in the art would have been motivated to conjugate the ligands taught by Cole (i.e., bisphosphonate or carboxylate amino acids), which are known and effective for selectively binding to mineral deposits such as kidney stones, to the nanoparticles of Kislev to better target kidney stones and provide improved delivery and localization of the nanoparticle treatment.
One of ordinary skill in the art would have had a reasonable expectation of success in making such a modification since Cole teaches that targeting ligands are known to be conjugated onto therapeutic nanoparticles and Kislev generally welcomes targeting molecules.
Claims 15-18, 22-24, 26-27, 29-30, 35-37, and 42-44 are rejected under 35 U.S.C. 103 as being unpatentable over Kislev and DiVito as applied to claims 15-18, 22-24, 26-27, 29-30, 35-37, and 43-44 above, and further in view of Aboutaleb H. (2016). Fluoroscopy free flexible ureteroscopy with holmium: Yttrium-aluminium-garnet laser lithotripsy for removal of renal calculi. Arab J Urol. 14(2):123-30 (PTO-892), hereinafter Aboutaleb.
The combined teachings of Kislev and DiVito are discussed above.
The combined teachings of Kislev and DiVito differ from that of the instant invention in that neither explicitly teach wherein the method is performed without image guidance as recited in claim 42.
Aboutaleb discloses the feasibility of access sheath insertion and ureteric stent placement without image guidance in flexible ureteroscopic lithotripsy with holmium:yttrium-aluminium-garnet laser for renal stones (abstract). These stones are increasingly being treated by flexible ureteroscopes with holmium:yttrium-aluminium-garnet (Ho:YAG) laser lithotripsy. Growing awareness of the radiation hazards associated with routine medical imaging and intraoperative exposure has prompted the search for methods to reduce patient, surgeon, and intraoperative team exposure. During flexible ureteroscopic lithotripsy, the placement of a ureteric access sheath exposes the patient to significant amounts of radiation. Thus, the goal is to insert the access sheath without the use of fluoroscopy (Intro). Overall, access sheath insertion without fluoroscopic guidance is feasible and reduces the risk of radiation exposure. Fluoroscopy free flexible URSL with Ho:YAG laser for the treatment of renal calculi is a safe and effective option (Conclusion).
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 perform the combined method of Kislev and DiVito without image guidance since Aboutaleb teaches that flexible ureteroscopic lithotripsy is feasible without image guidance and reduces radiation risk. The combined method of Kislev and DiVito teaches irradiation of nanoparticles by fishing a flexible laser up the urethra and placing the laser near the stone. DiVito also teaches the flexible laser may be a HoYAG laser, such as that used in Aboutaleb. One of ordinary skill in the art would have been motivated to insert the laser without image guidance in order to reduce the radiation risks associated with fluoroscopy, as taught by Aboutaleb. One of ordinary skill in the art would have had a reasonable expectation of success in performing the combined method without image guidance since Aboutaleb teaches that lithotripsy with a flexible Ho:YAG laser is safe and effective for the treatment of renal calculi without image guidance.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 15-18, 21-31, 35-37, and 39-44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 2 of U.S. Patent No. 9,475,028 in view of Kislev. The Obviousness Double Patenting rejection is appropriate because while the conflicting claims are not identical, the examined claims are not patentably distinct from the reference claims and would have been obvious over the reference claims in view of Kislev.
Conflicting claim 1 recites a method of localized heating within an article, comprising the steps of: disposing a plurality of functionalized fullerenes in or on at least one target region; and irradiating said functionalized fullerenes with electromagnetic radiation to convert said radiation to thermal energy wherein said thermal energy dissipates as a photoacoustic wave emanating from said functionalized fullerene comprising molecule; and inducing a change in physical state or a chemical reaction in said target region by said photoacoustic wave wherein an article comprising said target region is altered. Such a method reads on delivering photonic nanoparticles and irradiating said nanoparticles with electromagnetic radiation. The electromagnetic radiation may be ultraviolet, visible, infrared, microwave or radio wave (conflicting claim 4), all of which read on non-ionizing electromagnetic radiation.
The conflicting claims differ from the instant claims in that they do not specify that the target region is “in a vicinity of a kidney stone within a patient” or wherein the target region is altered “to fragment the kidney stone”.
Kislev discloses a method for inducing localized delivery of heat to a cell or a tissue comprises: a. administering a plurality of nanoparticles to the cell or tissue; and b. irradiating the nanoparticles administered to said cell or tissue by electromagnetic radiation ([0042]-[[0044]; claim 20). In one embodiment, the method is for reducing the size of or removing at least one stone from a kidney (claim 52), for example, to break (i.e., fragment) kidney stones ([0055]). Such a use inherently requires the nanoparticles to be delivered in a vicinity of the kidney stone within a patient.
It would have therefore been prima facie obvious to one of ordinary skill in the art to utilize the method of the conflicting claims as a method for localizing heat in the vicinity of a kidney stone, and wherein the target region is altered to fragment said kidney stone, since similar methods of localized delivery of heat via nanoparticles and electromagnetic radiation are known and routine in the art for treating kidney stones, as taught by Kislev. One of ordinary skill in the art could have used the known technique of the conflicting claims to treat kidney stones according to Kislev, which teaches a similar technique, to predictably yield the instant invention. One of ordinary skill in the art would have had a reasonable expectation of success in making such a modification since the conflicting claims broadly teach a “target region” which “is altered”, and Kislev teaches that similar methods of localized heat delivery are used for the breaking up of kidney stones.
Conclusion
No claims allowed.
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/SUSANNAH S ARMSTRONG/Examiner, Art Unit 1616
/SUE X LIU/Supervisory Patent Examiner, Art Unit 1616
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