DETAILED ACTION
Summary
Claims 1, and 5-20 are pending in the application. Claims 1, 5-12, and 14-20 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 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, and 5-9 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) over a time period of 10 min to 90 min (Col 13, lines 4-6), 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 if a half-life in plasma of the first therapeutic agent is ≥ 1 h, the time period for delivering the first therapeutic agent is completed 0 to 30 min prior to applying the LIPU (This limitation is contingent on the half-life in plasma being ≥ 1 h. By the broadest reasonable interpretation of the method, the half-life in plasma need not be ≥ 1 h, and as such this step does not need to occur (MPEP 2111.04(II))), and
wherein the LIPU results in an opening of a blood-brain barrier volume of 1-1500 cm3 (Col 9, lines 9-15), the time period for delivering the first therapeutic agent begins 0 to 30 min after applying the LIPU (Col 10, lines 18-22)+(Col 13, lines 4-6).
While Carpentier teaches wider range (10-120 min and <60 min), Carpentier is silent regarding a range of 0 to 30 minutes. However, it would have been obvious to one of ordinary skill in the art to choose a value of 0 to 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)).
While Carpentier teaches that the therapeutic agent is delivered after applying the LIPU, Carpentier is silent regarding wherein if 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 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 25 ms and a pulse repetition frequency of 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 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) over a time period of 10 min to 90 min (Col 13, lines 4-6), 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)
wherein if the half-life in plasma of the first therapeutic agent is < 1 h, the time period for delivering the first therapeutic agent begins 0to 30 min after applying the LIPU (This limitation is contingent on the half-life in plasma being ≥ 1 h. By the broadest reasonable interpretation of the method, the half-life in plasma need not be ≥ 1 h, and as such this step does not need to occur (MPEP 2111.04(II))).
Carpentier fails to explicitly teach wherein if a half-life in plasma of the first therapeutic agent is ≥ 1 h, the time period for delivering the first therapeutic agent is completed 0 to 30 min prior to applying the LIPU.
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 0 to 30 min 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 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).
Claims 14-17 are rejected under 35 U.S.C. 103 as being unpatentable over Carpentier in view of Shapiro (U.S PGPub 2019/0175763 A1).
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, and the LIPU is applied within 0 to 30 min after completion of delivery of the first therapeutic agent.
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, and the LIPU is therefore applied within 0 to 30 min after completion of delivery of the first therapeutic agent (i.e. after the injection) [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 17 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 microbubble solution (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).
Allowable Subject Matter
Claim 13 allowed.
The following is a statement of reasons for the indication of allowable subject matter: Claim 13 recites “the first therapeutic agent has a longer alpha half-life than the second therapeutic agent, the first therapeutic agent is delivered prior to the applying step, and the second therapeutic agent is delivered after the applying step”. This limitation, in combination with the other limitations, is not taught by the prior art without the benefit of improper hindsight reasoning.
Applicant’s arguments, see pages 12-13, section V, have been fully considered and are persuasive. Carpentier does not teach using multiple therapeutic agents. While Thompson does teach using multiple therapeutic agents, Thompson does not teach applying them at different times or using LIPU. While Shapiro details that different vectors can be applied at different times depending on the half-life of the vector, Shapiro would not suggest applying one vector before the application of ultrasound and another vector after the application of ultrasound without the benefit of improper hindsight reasoning. Mulder and Kazazi-Hysenmi were relied on to teach the alpha half-lives of different, and do not teach the claimed invention. Therefore, claim 13 is non-obvious over the prior art, and is allowable.
Response to Arguments
Applicant's arguments filed 5/11/2026 have been fully considered but they are not persuasive.
Applicant argues that the combination of Carpentier, Zhang, and Borga does not teach claim 1. The Examiner disagrees. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., different sequence of delivering the agent and LIPU depending on the plasma half-life) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). As claimed, the different plasma half-lives are contingent limitation. “The broadest reasonable interpretation of a method (or process) claim having contingent limitations requires only those steps that must be performed and does not include steps that are not required to be performed because the condition(s) precedent are not met” (MPEP 2111.04(II)). As these are mutually exclusive branches, only one of the therapeutic agent time periods need to be found to read on the claim. In this case, the combination teaches the scenario when the agent is applied after the LIPU. The Applicant further argues that the combination does not teach the specific time periods. The Examiner disagrees. As detailed above, the time periods are taught by the combination of references.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). While Zhang and Borga do not individually teach the claimed features, when view together and with the teachings of Carpentier, all the claimed features are taught by the references. Therefore, the rejection of claim 1 under 35 USC 103 under the combination of Carpentier, Zhang, and Borga is maintained.
Applicant argues that the combination of Carpentier, Beccaria, and Goldwirt does not teach claim 1. The Examiner disagrees. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., different sequence of delivering the agent and LIPU depending on the plasma half-life) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). As claimed, the different plasma half-lives are contingent limitation. “The broadest reasonable interpretation of a method (or process) claim having contingent limitations requires only those steps that must be performed and does not include steps that are not required to be performed because the condition(s) precedent are not met” (MPEP 2111.04(II)). As these are mutually exclusive branches, only one of the therapeutic agent time periods need to be found to read on the claim. In this case, the combination teaches the scenario when the agent is applied after the LIPU. The Applicant further argues that the combination does not teach the specific time periods. The Examiner disagrees. As detailed above, the time periods are taught by the combination of references.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). While Beccaria and Goldwirt do not individually teach the claimed features, when view together and with the teachings of Carpentier, all the claimed features are taught by the references.
Applicant argues that the Beccaria is not an analogous references as it pertains to a rabbit study. The Examiner disagrees. Beccaria is in the same realm of endeavor as the claimed invention (using ultrasound in combination with the application of drugs). As such, one of ordinary skill in the art would have considered the teachings of Beccaria. Furthermore, Beccaria teaches applying the therapeutic agent before application of the LIPU, and one of ordinary skill would have been motivated to make the configuration because it resulted in an improved amount of drug applied to the brain. Therefore, the combination does teach the claim, and the claim remains rejected under 35 USC 103.
Applicant argues that the combination of Carpentier and Shapiro fails to teach the features of amended claim 14. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Shapiro teaches applying the therapeutic agent before the ultrasound in [0177] (“In some embodiments, the microbubbles and vectors are co-injected within 1 minute before the focused ultrasound procedure. Vectors with long serum half-lives can be injected longer than 10 minutes before the FUS-BBBO procedure”). One of ordinary skill would further understand the injecting the vectors more than 10 min before would encompass starting the infusion 15 to 90 before, and ending the infusion within 0 to 30 min of applying the ultrasound. Therefore, the combination of references teaches the claimed invention, and the rejection under 35 USC 103 is maintained.
For similar reasons, the rejections of dependent claims 11-12, and 18-20 are also maintained.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN D MATTSON whose telephone number is (408)918-7613. The examiner can normally be reached Monday - Friday 9 AM - 5 PM PST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Pascal Bui-Pho can be reached at (571) 272-2714. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SEAN D MATTSON/Primary Examiner, Art Unit 3798
