DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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 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.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 6/16/26 has been entered.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
Claim 6, 9-11, 15-17, 21 and 22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2010010473 A1 to Shi et al. (Shi).
Shi discloses:
Regarding claim 6:
A method for enhancing the efficacy of a combined therapeutic treatment of gas-filled microvesicles and ultrasound for therapy in a subject, said method comprising the steps of:
a) administering a vasospasm inhibitor into a vascular system of the subject (see step “(ii) the administration of the therapeutic agent in an Ultrasound Dosage Form allowing release of the Therapeutic Agent to be affected by the application of ultrasound,” and further the reference indicates on page 7, line 20 – page 8, line 5 that “Therapeutic Agent” = bioactive agent = vasospasm inhibitors);
b) simultaneously or sequentially administering a suspension of gas-filled microvesicles into the vascular system of the subject (“(i) the administration of Ultrasound Particles that undergo a physical change when subjected to ultrasound;” and the reference further indicates on page 15, lines 10-20 that “Ultrasound Particles” = stable, flexible microbubbles (e.g., lipidshelled, perfluorocarbon gas-filled micro bubbles)); the applicants specification indicates gas-filled microvesicles= “The term includes what is known in the art as gas-filled liposomes, microbubbles, microspheres, microballoons or microcapsules” (specification. page 7, lines 24-31), wherein the vasospasm inhibitor is unbound to the gas-filled microvesicles (column 7, lines 21-22, “It is also conceivable that the Ultrasound Particles comprise the Therapeutic Agent in such a way as to be merely mixed together” or in other words unbound; further, steps of the process indicates the vasospasm inhibitor is unbound to the gas-filled microvesicles since the microvesicles and vasospasm inhibitor are administered at different steps);
c) applying therapeutic ultrasound to a region of interest of the subject (“(iii) the application of ultrasound so as to affect a physical change in at least some of the Ultrasound Particles, and (iv) the application of ultrasound so as to stimulate release of the Therapeutic Agent,”).
Regarding claim 9:
The method according to claim 6, wherein said suspension of gas-filled microvesicles is administered with a continuous infusion (“Herein, at least two known ultrasound agents are injected (or infused) one after another into bloodstream… A combination of multiple tracers and/or multiple drug carriers can also be employed”, page 15, lines 15-25) or by injecting at least one bolus.
Regarding claim 10:
The method according to claim 6, wherein step a) and step b) of said method are carried out sequentially ((“Herein, at least two known ultrasound agents are injected (or infused) one after another into bloodstream…”, page 15, lines 15-25 ).
Regarding claim 11:
The method according to claim 10, wherein step a) is carried out from 1 second to 15 minutes before the step b) (see page 15, lines 10-21 which discuss how the steps A and B of steps II and I (respectively) are repeated multiple times until the proper drug delivery is achieved at the proper location indicating that the steps are carrier out at least within 1 second of each other since the steps are continuously repeated).
Regarding claim 15:
The method according to claim 6, wherein said ultrasounds for therapy have a frequency comprised between 20 kHz and 70 MHz (“therefore 2 to 4 micron diameter particles are preferably chosen because the resonance lies in the medical diagnostic imaging frequency range of 1 to 10 MHz”, page 6, lines 20-25).
Regarding claim 21:
The method according to claim 6, wherein step a) and step b) of said method are carried out simultaneously (“a mixture of imaging and drug bearing contrast agents (i.e. Ultrasound Particles and Ultrasound Dosage Forms) is injected at the same time and selectively activated for imaging and drug release” on page 17, lines 8-12).
Regarding claim 22:
The method according to claim 6, wherein the vasospasm inhibitor is comprised in a separate pharmaceutical composition not physically connected to the gas-filled microvesicles suspension (column 7, lines 21-22, “It is also conceivable that the Ultrasound Particles comprise the Therapeutic Agent in such a way as to be merely mixed together” or in other words unbound; further, steps of the process indicates the vasospasm inhibitor is unbound to the gas-filled microvesicles since they are administered at different steps).
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.
Claim(s) 7-8 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2010010473 A1 to Shi et al. (Shi) as applied to claim 6 above, and further in view of US 20020188202 A1 to Hammesfahr.
Regarding claim 7:
Shi fails to disclose:
The method according to claim 6, wherein said vasospasm inhibitor is selected from the group consisting of dihydropyridine calcium blockers, a-blockers and nitrovasodilators.
Hammesfahr teaches:
A method for treating a stroke or multiple sclerosis (¶0015). The method further includes a step of determining a blood flow (¶0016) and a step of treating a patient with a Vasodilator/vasospasm inhibitor (¶0017). The reference further indicates the Vasodilator can include nitroglycerin (¶0028).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Shi to include nitroglycerin as a vasospasm inhibitor as taught by Hammesfahr. This is a simple substitution of one known element (vasospasm inhibitor as taught by Shi) for another (vasospasm inhibitor including nitroglycerin as taught by Hammesfahr) to obtain predictable results (to relax constricted blood vessels). Based on the 35 USC 112(b) rejection of claim 8 above, the claims have been interpreted to require anyone of dihydropyridine calcium blockers, a-blockers and nitrovasodilators, nimodipine, nifedipine, magnesium, prazosin and nitroglycerin.
Regarding claim 8:
All limitations of the claim are taught by the 35 USC 103 rejection of claim 7 by Shi and Hammesfahr:
The method according to claim 7, wherein said vasospasm inhibitor is selected from the group consisting of nimodipine, nifedipine, magnesium, prazosin and nitroglycerin (see the nitroglycerin as taught by Hammesfahr incorporated into Shi).
Claim(s) 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2010010473 A1 to Shi et al. (Shi) as applied to claim 6 above, and further in view of WO 2006094951 A1 to Gaud et al. (Gaud).
Regarding claim 12:
Shi fails to disclose:
The method according to claim6, wherein said ultrasounds for therapy have an acoustic pressure comprised between 100 and 900 kPa.
Gaud teaches:
A medical imaging system (column 3, lines 5-15) that include microvesicles (page 3, lines 25-30). The reference further indicates the microvesicles can be pulsed with ultrasound (column 4, lines 24-26). The reference also indicates that the acoustic pressure of the microvesicles can includes 20kPa and 500kPa.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Shi to further include the ultrasound therapy to have an acoustic pressure comprised between 20kPa and 500kPa (overlapping with 100 and 900 kPa) as taught by Gaud. This is a simple substitution of one known element (the acoustic pressure of the microvesicles of Shi) for another (20kPa and 500kPa as taught by Gaud) to obtain predictable results (to get the microvesicles to discharge the bioagent/ vasospasm inhibitor).
Claim(s) 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2010010473 A1 to Shi et al. (Shi) as applied to claim 6 above, and further in view of WO 9939738 A1 to Schneider et al. (Schneider).
Regarding claim 13:
Shi fails to disclose:
The method according to claim 6, wherein said ultrasounds for therapy have a pulse length comprised between 5 µs and 60 s.
Schneider teaches:
A method of applying ultrasound pulses (see abstract) to gas filled microvesicles (see abstract). The reference further indicates the pulse length can be 10 µs (page 10, lines 1-5).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Shi to use a pulse length of 10 µs as taught by Schneider to burst the microvesicles (page 3, lines 30-35).
Claim(s) 14 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2010010473 A1 to Shi et al. (Shi) as applied to claim 6 above, and further in view of EP 1714642 A1 to Bettinger et al. (Bettinger).
Regarding claim 14:
Shi fails to disclose:
The method according to claim6, wherein said ultrasounds for therapy are applied for a time comprised between 1 second and 170 minutes.
Bettinger teaches:
A method of comprising gas filled microcapsules and a bioactive agent, useful for an ultrasound-mediated delivery of said bioactive agent. The reference further teaches that the ultrasound exposure can go from a few seconds to up to an hour (page 15, lines 35-40) to achieve the most effective ultrasound enhanced delivery of the bioactive agent.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Shi to further include ultrasound exposure for a time of a few seconds to an hour as taught by Bettinger to achieve the most effective ultrasound enhanced delivery of the bioactive agent (Bettinger, page 15, lines 35-40).
Claim(s) 16 and 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2010010473 A1 to Shi et al. (Shi) as applied to claim 6 above, and further in view of WO 2005063305 A1 to Schneider et al. (Schneider).
Regarding claim 16:
Shi fails to disclose:
The method according to claim 6, further comprising administering a bioactive agent into the vascular system of the subject, wherein the bioactive agent is different from the vasospasm inhibitor.
Schneider teaches:
A method that includes a bioactive agent into the vascular system of the subject. Further, the bioactive agent is within the structure of said gas-filled microvesicles (column 1, lines 1-10 and column 8, lines 25-30).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Shi to further include a bioactive agent within the gas-filled microvesicles of Shi as taught by Schneider to improve the delivery of drugs/medication (column 1, lines 1-10).
Regarding claim 17:
All limitations of the claim are taught by the 35 USC 103 rejection of claim 16 by Shi and Schneider:
The method according to claim 16, wherein said bioactive agent is within the structure of said gas-filled microvesicles (see the bioactive agent within the gas-filled microvesicles as taught by Schneider and incorporated into Shi).
Response to Arguments
Applicant's arguments filed 6/16/26 have been fully considered but they are not persuasive.
Regarding the 35 USC 102 rejection of claim 6:
The applicant has argued that the above rejection no longer reads on the claim because of the amended limitation “wherein the vasospasm inhibitor is unbound to the gas-filled microvesicles” in line 9 of claim 6. However, as indicated above the Shi reference indicates the vasospasm inhibitor is separate from the microvesicles (column 7, lines 21-22, “It is also conceivable that the Ultrasound Particles comprise the Therapeutic Agent in such a way as to be merely mixed together” or in other words unbound; further, steps of the process indicates the vasospasm inhibitor is unbound to the gas-filled microvesicles since the microvesicles and vasospasm inhibitor are administered at different steps).
Regarding the 35 USC 102 rejection of claim 16:
The applicant’s amendments to the claims have overcome the previous rejection and for this reason it has been withdrawn. However, a new 35 USC 103 rejection has been made in its place.
Regarding the 35 USC 112(a) claim rejections:
The applicant’s amendments to the claims have addressed the previous rejections and for this reason they have been withdrawn.
Conclusion
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/WESLEY G HARRIS/Examiner, Art Unit 3783
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