DETAILED ACTION
Summary
Claims 1-20 are pending in the application. Claims 8 and 19-20 are rejected under 35 USC 112(b). Claims 1-20 are rejected under 35 USC 103.
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 .
Claim Objections
Claim 18 objected to because of the following informalities:
Claim 18 recites “60 min. or less.”. It should recites “60 minutes or less”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 8 and 19-20 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 8 recites “about 25 ms”. There is nothing in the specification which suggests what is encompassed by “about”. Clarification is required. For the purposes of examination, “about 25 ms” will be interpreted as within 20% of 25 ms.
Claim 8 recites “about 0.5 Hz to 1 Hz”. There is nothing in the specification which suggests what is encompassed by “about”. Clarification is required. For the purposes of examination, “about 0.5 Hz to 1 Hz” will be interpreted as within 20% of 0.5 Hz as the first endpoint of the range, and within 20% of 1 Hz as the other endpoint of the range.
Claim 19 recites the limitation "the ultrasound transducer" in lines 2-3. There is insufficient antecedent basis for this limitation in the claim. For the purposes of examination, the ultrasound transducer will be interpreted as “an ultrasound transducer”.
Claim 19 recites the limitation "the carboplatin" in line 4. There is insufficient antecedent basis for this limitation in the claim. For the purposes of examination, the carboplatin will be interpreted as being the first therapeutic agent.
Claim 19 recites the limitation "the ultrasound contrast agent" in line 6. There is insufficient antecedent basis for this limitation in the claim. For the purposes of examination, the ultrasound contrast agent will be interpreted as referring to the microbubble solution.
All claims dependent from the above claims rejected under 35 USC 112(b) are also rejected, as the limitations of the dependent claims fail to cure the deficiencies identified above.
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 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.
Claims 1-2, and 4-9 are rejected under 35 U.S.C. 103 as being unpatentable over Carpentier et al. (U.S Patent 10,981,021 B2) in view of Zhang et al. (Zhang, Daniel Y., et al. "Ultrasound-mediated delivery of paclitaxel for glioma: a comparative study of distribution, toxicity, and efficacy of albumin-bound versus cremophor formulations." Clinical cancer research 26.2 (2020): 477-486.) and Borga et al. (Borgå, Olof, et al. "Maximum tolerated dose and pharmacokinetics of paclitaxel micellar in patients with recurrent malignant solid tumours: a dose-escalation study." Advances in Therapy 36.5 (2019): 1150-1163.)
Regarding Claim 1, Carpentier teaches a method for delivering a therapeutic agent to a human brain (Abstract)+(Col 9, lines 15-21), the method comprising:
delivering systemically a first therapeutic agent to a human (Col 10, lines 10-22)+(Col 12-13, lines 65-6), and
applying low intensity pulsed ultrasound (LIPU) (Col 6, lines 6-45)+(Col 7, lines 27-52) (the ultrasound sequence parameters described in the section is LIPU, as recognized on page 8, line 21, of the specification) in the presence of circulating microbubbles to a brain of the human (Col 7-, lines 64-5)+(Col 8, lines 14-25) for a period of 1 µs to 20 min (Col 12, lines 41-43) (activated for 2.5 minutes),
wherein the LIPU results in an opening of a blood-brain barrier volume of 1-1500 cm3 (Col 9, lines 9-15), the first therapeutic agent is delivered after applying the LIPU (Col 10, lines 18-22).
While Carpentier teaches that the therapeutic agent is delivered after applying the LIPU, Carpentier is silent regarding the half-life in plasma of the first therapeutic agent is < 1 h.
Zhang teaches a method for applying paclitaxel for treating a brain disorder (Abstract). This system uses ultrasonic BBB disruption for better administration of paclitaxel (Pg. 478-479) (Sonication procedure).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the combined system to apply paclitaxel, as taught by Zhang, because this provides a safe and efficacious way of treating glioma, as recognized by Zhang (Pg. 485, Col 2, ¶ 1).
Zhang is silent regarding the half-life of paclitaxel.
Borga teaches a paclitaxel formulation (Abstract). This formulation has a half-life of 0.55 h (less than 1 hour) (Abstract) (Table 3, t1/2).
It would have been obvious to one of ordinary skill in the art before the effective filing date to substitute the paclitaxel of the combination with a drug having a half-life less than 1 hour, as taught by Zhang, as the substitution for one known paclitaxel formulation with another yields predictable results to one of ordinary skill in the art. One of ordinary skill would have been able to carry out such a substitution, and the results of using a drug with a half-life of less than 1 hour are reasonably predictable.
Regarding Claim 2, the combination of references teaches the invention substantially as claimed. Carpentier further teaches wherein a time period between completion of the delivering step and the applying step is not more than 45 min (Col 10, lines 18-22). While Carpentier teaches wider range (10-120 min), Carpentier is silent regarding a range of less than 45 minutes. However, it would have been obvious to one of ordinary skill in the art to choose a value less of less than 45 min, as taught by Carpentier, as "[A] prior art reference that discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness." In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003). (MPEP 2144.05(I)).
Regarding Claim 4, the combination of references teaches the invention substantially as claimed. Carpentier further teaches wherein the first therapeutic agent having a half-life in plasma of < 1 h is delivered over a period of time starting 0 to 30 min after applying the LIPU (Col 10, lines 18-22). While Carpentier teaches wider range (10-120 min), Carpentier is silent regarding a range of less than 0-30 minutes. However, it would have been obvious to one of ordinary skill in the art to choose a value less of less than 30 min, as taught by Carpentier, as "[A] prior art reference that discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness." In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003). (MPEP 2144.05(I)).
Regarding Claim 5, the combination of references teaches the invention substantially as claimed. Carpentier further teaches wherein the LIPU is applied to the brain at a pressure level of 0.5 MPa or higher at a resonance frequency ranging from 0.5 to 1.5 MHz (Col 2, lines 40-47).
Regarding Claim 6, the combination of references teaches the invention substantially as claimed. Carpentier further teaches wherein the ultrasound pressure is between 0.5 MPa and 2.00 MPa (Col 2-3, lines 64-2).
Regarding Claim 7, the combination of references teaches the invention substantially as claimed. Carpentier further teaches wherein the LIPU has a mechanical index (MI) from 0.1 to 2.00 (Col 3, lines 3-5).
Regarding Claim 8, the combination of references teaches the invention substantially as claimed. Carpentier further teaches wherein the LIPU is applied in pulses of duration about 25 ms and a pulse repetition frequency of about 0.5 Hz to 1 Hz (Col 7, lines 49-53) (23 ms is “about” 25 ms).
Regarding Claim 9, the combination of references teaches the invention substantially as claimed. Carpentier further teaches wherein the LIPU is applied by an ultrasound transducer implanted in a burr hole or bone flap in a skull of the human (Col 3, lines 16-19).
Claims 1, 3, and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Carpentier in view of Beccaria et al. (Beccaria, Kevin, et al. "Ultrasound-induced opening of the blood-brain barrier to enhance temozolomide and irinotecan delivery: an experimental study in rabbits." Journal of neurosurgery 124.6 (2016): 1602-1610.) and Goldwirt et al. (Goldwirt, Lauriane, et al. "Irinotecan and temozolomide brain distribution: a focus on ABCB1." Cancer chemotherapy and pharmacology 74.1 (2014): 185-193.).
Regarding Claim 1, Carpentier teaches a method for delivering a therapeutic agent to a human brain (Abstract)+(Col 9, lines 15-21), the method comprising:
delivering systemically a first therapeutic agent to a human (Col 10, lines 10-22)+(Col 12-13, lines 65-6), and
applying low intensity pulsed ultrasound (LIPU) (Col 6, lines 6-45)+(Col 7, lines 27-52) (the ultrasound sequence parameters described in the section is LIPU, as recognized on page 8, line 21, of the specification) in the presence of circulating microbubbles to a brain of the human (Col 7-, lines 64-5)+(Col 8, lines 14-25) for a period of 1 µs to 20 min (Col 12, lines 41-43) (activated for 2.5 minutes),
wherein the LIPU results in an opening of a blood-brain barrier volume of 1-1500 cm3 (Col 9, lines 9-15).
Carpentier fails to explicitly teach the first therapeutic agent is delivered prior to applying the LIPU if a half-life in plasma of the first therapeutic agent is ≥ 1 h.
Beccaria teaches a method of treating the brain through the blood brain (Abstract). This system treats the brain using Irinotecan (CPT-11) or TMZ (Pg. 1603, Col 1, ¶ 4). This system delivers the therapeutic agent prior to ultrasound sonication (Fig. 1) (Pg. 1603-1604, Drug Injection Protocols).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the combined system to inject the drug before sonication, as taught by Beccaria, because this improves drug delivery to the brain, as recognized by Beccaria (Pg. 1608, Conclusion).
The combination fails to explicitly teach a half-life in plasma of the first therapeutic agent is ≥ 1 h.
Goldwirt teaches different drugs for treating glioblastoma (Abstract). This system uses CPT-11, which has a plasma half-life of over 1 hour (Pg. 189, Table 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date to substitute the drug of the combination with CPT-11 with a half-life of over 1 hour, as taught by Goldwirt, as the substitution for one known chemotherapy drug with another yields predictable results to one of ordinary skill in the art. One of ordinary skill would have been able to carry out such a substitution, and the results of using CPT-11 with a half-life of over 1 hour are reasonably predictable.
Regarding Claim 3, the combination of references teaches the invention substantially as claimed. Carpentier fails to explicitly teach wherein the LIPU is applied within 0 to 30 min after completion of delivery of the first therapeutic agent having a half-life in plasma of ≥ 1 h.
Beccaria further teaches the system delivers the therapeutic agent prior 5 minutes prior to ultrasound sonication (Fig. 1) (Pg. 1603-1604, Drug Injection Protocols).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the combined system to inject the drug before sonication, as taught by Beccaria, because this improves drug delivery to the brain, as recognized by Beccaria (Pg. 1608, Conclusion).
Regarding Claim 10, the combination of references teaches the invention substantially as claimed. Carpentier further teaches the first therapeutic agent is carboplatin (Col 11, lines 5-10).
Carpentier fails to explicitly teach wherein the first therapeutic agent is temozolomide, or irinotecan.
Beccaria further teaches the therapeutic agent can be temozolomide or irinotecan (Pg. 160, Col 1, ¶ 4).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the combined system to use temozolomide or irinotecan, as taught by Beccaria, because this provides improved treatment to the brain, as recognized by Beccaria (Pg. 1608, Conclusion).
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Carpentier in view of Goldwirt and Beccaria as applied to claim 10 above, and further in view of White et al. (White, Edward, et al. "An evaluation of the safety and feasibility of convection-enhanced delivery of carboplatin into the white matter as a potential treatment for high-grade glioma." Journal of neuro-oncology 108.1 (2012): 77-88.)
Regarding Claim 11, the combination of references teaches the invention substantially as claimed. The combination fails to explicitly teach wherein the first therapeutic agent is delivered by infusion over a period not exceeding 60 min.
White teaches a system for treating glioblastoma (Abstract). This system delivers the drug via infusion for less than 60 min (Pg. 79-80, Pig infusion procedure and apparatus).
It would have been obvious to one of ordinary skill in the art to substitute the delivery of the drug of the combination to be an infusion for less than 60 minutes, as taught by White, as the substitution for one known method for administering a drug with another yields predictable results to one of ordinary skill in the art. One of ordinary skill would have been able to carry out such a substitution, and the results of infusing the drug for less than 60 minutes are reasonably predictable.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Carpentier in view of Goldwirt and Beccaria as applied to claim 10 above, and further in view of Thompson et al. (Thompson, Eric M., et al. "Treatment with bevacizumab plus carboplatin for recurrent malignant glioma." Neurosurgery 67.1 (2010): 87-93.).
Regarding Claim 12, the combination of references teaches the invention substantially as claimed. The combination fails to explicitly teach delivering a second therapeutic agent different from the first therapeutic agent.
Thompson teaches a method for treating glioma (Abstract). This system uses two different therapeutic agents to treat the glioma (Pg. 88, Col 2, ¶ 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the combined system to use more than one therapeutic agent, as taught by Thompson, because this provides improved chances for the survival of the patient, and is the treatment of choice for malignant gliomas, as recognized by Thompson (Pg. 92, Col 1, ¶ 2-3).
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Carpentier in view of Thompson, Shapiro (U.S PGPub 2019/0175763 A1), Mulder et al.(Mulder, Paula OM, et al. "Pharmacokinetics of carboplatin at a dose of 750 mg m-2 divided over three consecutive days." British journal of cancer 61.3 (1990): 460-464.) and Kazazi-Hyseni et al. (Kazazi-Hyseni, Filis, Jos H. Beijnen, and Jan HM Schellens. "Bevacizumab." The oncologist 15.8 (2010): 819.).
Regarding Claim 13, Carpentier teaches a method for delivering a therapeutic agent to a human brain (Abstract)+(Col 9, lines 15-21), the method comprising:
applying low intensity pulsed ultrasound (LIPU) (Col 6, lines 6-45)+(Col 7, lines 27-52) (the ultrasound sequence parameters described in the section is LIPU, as recognized on page 8, line 21, of the specification) in the presence of circulating microbubbles to a brain of the human (Col 7-, lines 64-5)+(Col 8, lines 14-25) for a period of 1 µs to 20 min (Col 12, lines 41-43) (activated for 2.5 minutes),
delivering systemically a second therapeutic agent to the human (Col 10, lines 10-22)+(Col 12-13, lines 65-6)
wherein the LIPU results in an opening of a blood-brain barrier volume of 1-1500 cm3 (Col 9, lines 9-15),
the second therapeutic agent is delivered after the applying step (Col 12-13, lines 65-6).
Carpentier fails to explicitly teach delivering systemically a first therapeutic agent to a human.
Thompson teaches a method for treating glioma (Abstract). This system uses two different therapeutic agents to treat the glioma, bevacizumab and intravenous carboplatin (Pg. 88, Col 2, ¶ 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the combined system to use more than one therapeutic agent, as taught by Thompson, because this provides improved chances for the survival of the patient, and is the treatment of choice for malignant gliomas, as recognized by Thompson (Pg. 92, Col 1, ¶ 2-3).
The combination is silent regarding the first therapeutic agent is delivered prior to the applying step.
Shapiro teaches a method for acoustically treating the brain (Abstract). This system administers the treatment before the application of ultrasound, or after the application of ultrasound, depending on the half-life of treatments [0177]. Serums with longer half lives can be administered long before the application of ultrasound, while serums with shorter half lives can be administered right after the ultrasound [0177].
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the combined system to have the treatment with the longer half life administered before the ultrasound, and the serum with the shorter half life administered after the ultrasound, as taught by Shapiro, because this allows the appropriate concentration of the treatment agent to reach the brain to achieve the desired effect, as recognized by Shapiro [0173].
The combination is silent regarding the alpha half life of the first therapeutic being larger than the second therapeutic.
Mulder teaches the alpha half life of carboplatin is around 70 min (Pg. 462, Table II).
It would have been obvious to one of ordinary skill in the art before the effective filing date to substitute the carboplatin of the combination with carboplatin with an alpha half life around 70 minutes, as taught by Mulder, as the substitution for one known carboplatin with another yields predictable results to one of ordinary skill in the art. One of ordinary skill would have been able to carry out such a substitution, and the results of using carboplatin with a half-life of 70 minutes are reasonably predictable.
The combination is silent regarding the alpha half-life of the first therapeutic being greater than the second therapeutic.
Kazazi-Hysenmi teaches bevacizumab has a half-life of around 20 days (Pg 821, Pharmacokinetics).
It would have been obvious to one of ordinary skill in the art to substitute the bevacizumab of the combination to have a half-life of 20 days, as taught by Kazazi-Hysenmi, as the substitution for one known bevacizumab with another yields predictable results to one of ordinary skill in the art. One of ordinary skill would have been able to carry out such a substitution, and the results of using bevacizumab with a larger half-life than carboplatin are reasonably predictable. One of ordinary skill would recognize that, in the combination, bevacizumab with the larger half life would be administered before the application of ultrasound, and carboplatin with the shorter half life would be administered after, as suggested by Shapiro.
Claims 14-17 are rejected under 35 U.S.C. 103 as being unpatentable over Carpentier in view of Shapiro.
Regarding Claim 14, a method for treating a brain disorder in a human (Abstract)+(Col 9, lines 15-21), the method comprising:
delivering a first therapeutic agent systemically to a human suffering from a brain disorder (Col 10, lines 10-22)+(Col 12-13, lines 65-6)+(Table 1),
administering to the human a microbubble solution (Col 12, lines 53-65), and
applying low intensity pulsed ultrasound (LIPU) to a brain of the human (Col 6, lines 6-45)+(Col 7, lines 27-52) (the ultrasound sequence parameters described in the section is LIPU, as recognized on page 8, line 21, of the specification) for a period of 1 min to 30 min (Col 12, lines 41-43) (activated for 2.5 minutes),
wherein the LIPU results in an opening of a blood-brain barrier volume of 1-1500 cm3 (Col 9, lines 9-15).
Carpentier fails to explicitly teach the first therapeutic agent is delivered by infusion starting at 15 to 90 min prior to applying the LIPU.
Shapiro teaches a method for acoustically treating the brain (Abstract). This system administers the treatment longer than 10 minutes before the application of ultrasound, depending on the half-life of treatments [0177].
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the combined system to have the treatment administered before the ultrasound, as taught by Shapiro, because this allows the appropriate concentration of the treatment agent to reach the brain to achieve the desired effect, as recognized by Shapiro [0173]. It further would have been obvious to one of ordinary skill in the art to choose a value between 15 to 90 min, as Shapiro teaches a range of greater than 10 min, and "[A] prior art reference that discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness." In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003). (MPEP 2144.05(I)).
Regarding Claim 15, the combination of references teaches the invention substantially as claimed. Carpentier further teaches wherein the brain disorder is cancer (Col 9, lines 28-47) (Table 1, the patients have tumors ) and the first therapeutic agent is carboplatin delivered at a dose of AUC3-7 (Col 12-13, lines 65-6).
Regarding Claim 16, the combination of references teaches the invention substantially as claimed. Carpentier further teaches wherein the LIPU is applied for 3 to 5 min (Col 7, lines 43-48).
Regarding Claim 17, the combination of references teaches the invention substantially as claimed. Carpentier further teaches wherein the LIPU is applied by an ultrasound transducer implanted in a burr hole or bone flap in a skull of the human (Col 3, lines 16-19).
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Carpentier in view of Shapiro as applied to claim 14 above, and further in view of Stewart et al. (Stewart, David J., et al. "Phase I study of intracarotid administration of carboplatin." Neurosurgery 30.4 (1992): 512-517.).
Regarding Claim 18, the combination of references teaches the invention substantially as claimed. The combination of references fails to explicitly teach wherein the first therapeutic agent is infused through a catheter for a period of 60 min. or less.
Stewart teaches a method for administering carboplatin (Abstract). The carboplatin is infused using a catheter of 30 minutes (Abstract) (Pg. 4, ¶ 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date to substitute the method of administering carboplatin with an infusion which occurs over 30 minutes, as taught by Stewart, as the substitution for one known method for administering carboplatin with another yields predictable results to one of ordinary skill in the art. One of ordinary skill would have been able to carry out such a substitution, and the results of infusing carboplatin for less than 60 min are reasonably predictable.
Claims 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Carpentier in view of Shapiro and Stewart as applied to claim 18 above, and further in view of Chen et al (U.S PGPub 2015/0045724 A1) and Gorski (Gorski, Lisa A. "The 2016 infusion therapy standards of practice." Home healthcare now 35.1 (2017): 10-18.).
Regarding Claim 19, the combination of references teaches the invention substantially as claimed. Carpentier further teaches preparing the microbubble solution (Pg. 12, lines 53-64) (by using the microbubble solution, it must have been prepared), connecting the ultrasound transducer electrically to a radio frequency generator (Col 12, lines 33-52), injecting the microbubble solution (Pg. 12, lines 53-64), and the LIPU is applied for a period of 4.5 min after injection of the ultrasound contrast agent (Col 7, lines 43-48)+ (Pg. 12, lines 53-64).
While Carpentier is silent the LIPU is applied for 4.5, it would have been obvious to one of ordinary skill to perform the LIPU for 4.5 min because Carpentier teaches using a range of 1 to 10 minutes and "[A] prior art reference that discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness." In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003). (MPEP 2144.05(I)).
Carpentier fails to explicitly teach wherein the carboplatin is delivered by infusion for 30 min through the catheter.
Stewart teaches a method for administering carboplatin (Abstract). The carboplatin is infused using a catheter of 30 minutes (Abstract) (Pg. 4, ¶ 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date to substitute the method of administering carboplatin with an infusion which occurs over 30 minutes, as taught by Stewart, as the substitution for one known method for administering carboplatin with another yields predictable results to one of ordinary skill in the art. One of ordinary skill would have been able to carry out such a substitution, and the results of infusing carboplatin for less than 60 min are reasonably predictable.
The combination fails to explicitly teach injecting the microbubble solution into the catheter.
Chen teaches a method for drug delivery (Abstract). This system injects the microbubble solution into the catheter and delivers the microbubble solution after delivering the therapeutic agent [0080]+[0082] (Fig. 13).
It would have been obvious to one of ordinary skill in the art before the effective filing date to substitute the method of delivering the agents, with using a catheter, as taught by Chen, as the substitution for one known method for delivering microbubbles with another yields predictable results to one of ordinary skill in the art. One of ordinary skill would have been able to carry out such a substitution, and the results of using the catheter the deliver the microbubbles are reasonably predictable.
The combination fails to explicitly teach flushing the catheter with saline for a period of 20 s to 10 min and delivering the carboplatin prior to the flushing step.
Gorski teaches standards for using an infusion catheter (Abstract). The standards require that the catheter is flushed between the infusion of medications (Pg. 16, Flushing and Locking).
It would have been obvious to one of ordinary skill in the art before the effective filing date to flush the infusion catheter, as taught by Gorski, because to assess catheter function and prevent complications, as this improves the safety and efficacy of the procedure, as recognized by Gorski (Pg. 16, Flushing and Locking). While Gorski is silent regarding flushing the catheter from 20 s to 10 min, is would have been obvious to one of ordinary skill in the art to flush the catheter over a period for 20 s to 10 min through routine experimentation in determining the optimal amount of time to fully flush the medicament in the catheter. One of ordinary skill would have been motivated to optimize the optimal amount of time to flush the catheter, and would have had a reasonable expectation of success optimizing the period to be between 20 s to 10 min. One of ordinary skill would recognize the combination would have the carboplatin delivered before the flushing step, as it is delivered before the microbubble is delivered, as suggested by Chen.
Regarding Claim 20, the combination of references teaches the invention substantially as claimed. Carpentier further teaches obtaining a magnetic resonance image of the brain of the human to determine an extent of blood-brain barrier volume opening (Col 8-9, lines 61-8).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Walczak et al. (U.S Patent 10,478,120 B2), which teaches a method for administering a therapeutic through the blood brain barrier.
Zhang et al. (U.S PGPub 2022/0161013 A1), which teaches a method for treating the central nervous system after ultrasonically opening the blood brain barrier.
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/SEAN D MATTSON/ Primary Examiner, Art Unit 3798