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 .
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.
Claim(s) 1,3-15 is/are rejected under 35 U.S.C. 103 as being unpatentable over the combined disclosures of combined disclosures of van Elk et al (Alginate Microspheres Containing Temperature Sensitive Liposomes (TSL) for MR-Guided Embolization and Triggered Release of Doxorubicin, PLOS, November 11, 2015) in view of Cascone et al (Microencapsulation effectiveness of small active molecules in biopolymer by ultrasonic atomization technique, Drug Development and Industrial Pharmacy, 38:12, 1486-1493 hereafter Cascone) and Kennedy et al (US 2008/0075777 hereafter Kennedy).
Van Elk discloses a temperature-sensitive liposomes comprising an atomizing a liposome/alginate into a curing solution comprising an alginate cross -linker and isolating the resulting microspheres having an average diameter of about 50 µm (abstract, Figure 2, Figure 4), meeting elements of claim 1, 12, 14 and 15. The curing solution which crosslinks the alginate comprising cations such as zinc and barium (pg 6), meeting limitations of claims 1, 6 and 7. The liposome/alginate is present in a ratio of 1:1(pg 6) meeting limitations of claim 9. The liposomes comprises chemotherapeutic agent and thermotherapeutic such as doxorubicin and a imagine agent comprising Gd (pg. 8), meeting limitations of claims 10 and 11. The liposomes are injected directly into a tumor for treatment (Animal Model, pg. 8, pg. 15).
While van Elk discloses a method of preparing alginate liposomes comprising spraying a liposome/alginate solution into a crosslinking solution through a nozzle with nitrogen gas. The reference is however silent to the use of an ultrasonic nozzle as an atomizer, however the use of such method components in the making of liposome microspheres is well known in the art as seen in the Cascone study.
Cascone discloses a method of making drug loaded microspheres [abstract]. The method comprises using an ultrasonic atomizer at a frequency of 20 kHz spray an alginate aqueous solution into a calcium chloride solution forming microspheres [pg. 1488], meeting limitations of claim 3, 4 and 6-8. It would have been obvious to include this nozzle into the preparation method of van Elk as they solve the same problem.
The combination discloses a method of preparing a liposome using an ultrasonic nozzle, but is silent to the specific frequency of claim 3. The use of specific frequency for the use of ultrasonic nozzles is known in the art as seen in the Kennedy patent.
Kennedy discloses a means of making microparticles using an ultrasonic nozzle at a frequency of 25 kHz and at a height of 4 cm [abstract, 0150, Figure 2]. The nozzle sprayed directly into a solution forming microspheres from 20-50 microns [Figure 5]. The nozzle allows for control over the particle size and would have been an obvious addition to the process of van Elk as they solve the same problem.
With these aspects in mind, it would have been obvious to combine the prior art to produce a method of preparing liposomes using an ultrasonic nozzle in order to tightly control the size of the size of the liposomes. It would have been obvious to include the commonly available ultrasonic nozzle of Cascone in order produce more uniform particles. This combination would have been obvious as van Elk and Donsky solve the same problem of making alginate liposomes. It would have been obvious to include the ultrasonic nozzle of Kennedy into the preparation in or to produce large quantities of the liposomes at a higher frequency for industrial production. One of ordinary skill in the art would have been motivated to combine the prior art in order to produce liposomes on an industrial scale.
Response to Arguments
Applicant's arguments filed 12/15/25 have been fully considered but they are not persuasive. Applicant argues that the combination of van Elk, Cascone and Kennedy do not render the claims obvious as they do not disclose all of the elemnts of the instant claims.
As discussed above it remains the position of the Examiner that the combination of van Elk, Caruso and Kennedy, render the claims obvious. Van Elk discloses a method for producing liposome containing alginate comprising atomizing a temperature sensitive liposome alginate solution using a nozzle into a curing solution comprising alginate crosslinker that is a cation, isolating the liposome where the microspheres are about 50 microns. The curing solution is a barium salt and the liposome/alginate is present in the same ratio as the instant claims. The nozzle uses nitrogen glass, however is not described as an ultrasonic nozzle. The method produces microspheres of the same size, components and for the same use, by injecting them into tumors for treatment and imaging. The use of an ultrasonic nozzle to make microspheres is well known the art as seen in Kennedy, where nitrogen gas is used through an ultrasonic nozzle to generate microspheres from 20-50 microns. The frequency is 25kHz at a height of 4 cm. This allows for mass production of microspheres comprising alginate as a polysaccharide as it is biocompatible for injection. Cascone provides the specific curing agent for the liposomes while also using an ultrasonic nozzle to form liposomes. It would have been obvious to modify the process of van Elk to include the ultrasonic nozzle as seen in Kennedy as they both use nitrogen gas to propel the fluid. There would have been a reasonable expectation of success as they use the same gas and materials, specifically alginate. It would have been obvious to modify van Elk as seen in the Cascone as, again they solve a similar problem and van Elk is suggestive of cation curing agents and the inclusion of calcium chloride would have been useful in producing stable microspheres. It would have been obvious to include the commonly available ultrasonic nozzle of Cascone in order produce more uniform particles. This combination would have been obvious as van Elk and Donsky solve the same problem of making alginate liposomes. It would have been obvious to include the ultrasonic nozzle of Kennedy into the preparation in or to produce large quantities of the liposomes at a higher frequency for industrial production. One of ordinary skill in the art would have been motivated to combine the prior art in order to produce liposomes on an industrial scale.
Conclusion
THIS ACTION IS MADE FINAL. 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 MICAH PAUL YOUNG whose telephone number is (571)272-0608. The examiner can normally be reached Monday through Friday, 9:00 am to 5:30 pm.
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/MICAH PAUL YOUNG/Primary Examiner, Art Unit 1618