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 .
Response to Amendments
Applicant did not amend the claims.
Response to Arguments
Applicant argues that Sawhney teaches away from using Lipidiol®. Further, Applicant argues that there is no motivation to combine the claimed references.
The examiner notes that Sawhney teaches treating the claimed subject population with a biodegradable embolic material. While Sawhney teaches an advantage of embolic agents, it does not provide a teaching away of Lipidiol®. Further, the references as a whole teach using Lipidiol® and address potential shortcomings described by Sawhney.
The prior art teaches that biodegradable embolic compositions that can be used to treat the claimed conditions including hypervascularization formed in response to chronic inflammation in a musculoskeletal vasculature as well as to treat hypervascularization associated with many cancers. The purpose of each reference is to mitigate vasculature and blood flow to tumors and/or excessive vasculature associated with chronic inflammatory cites. While Lipidiol® is not required by Sawhney, it is taught as usable to mitigate hypervascularization and would be understood as usable in view of Dreher and Caroline each teaching use of Lipidiol® and other iodized oils. Sawhney teaches that it is not as predictable as other embolics.
More importantly, while it is true that Sawhney teaches that Lipidiol® is not as predictable as starch beads, a POSA would still understand that it can be used. A preference or advance over a previous standard is not a teaching away which requires more of an explicit disparagement. Even further, Dreher not only recognizes stability issues that can be associated with Lipidiol® (par. 7), but is predicated on a developed emulsion formulation with Lipidiol® that has increased stability by incorporates iodine containing particles into a composition. Dreher states: “The preparation has the potential to provide embolisation of both the arterial and portal venous supply to the tumour, and to reduce exposure of the general circulation to incorporated drug and to provide more predictable pharmacokinetics and improved local delivery.” Par. 8. Thus, Dreher resolves the stability issues described by Sawhney, but also teaches Lipidiol® as being particularly advantageous due to its’ radiopacity due to iodine content. See par. 42. Therefore, the main reason that Sawhney prefers other embolics is ameliorated by the teachings of Dreher.
As such, the prior art provides a POSA a motivation to use an embolic composition having the claimed properties, including one that uses Lipidiol® in view of Dreher because it does so by improving composition predictability while keeping the advantages bestowed by the use of Lipidiol®. As such, a POSA would understand that such composition can be used to treat hypervascularization that is associated with tumors as well as musculoskeletal vasculature associated with other chronic conditions. Even further, the broadest of instant claims do not preclude
Similarly, Caroline teaches chemoembolization procedures for treating cancer using Lipidiol® containing compositions that comprise similar concentrations of oil, water, iodine, and having a comparable viscosity.
The prior art as a whole teaches the use of embolic compositions comprising a claimed iodine containing oil component. These composition can be used to treat conditions involving hypervascularization, including inflammatory conditions of musculoskeletal vasculature as well as hypervascularization that increases blood flow to a tumor. Tumors that can be treated are not limited and would thus be inclusive of musculoskeletal tumors. Each of the cited prior art references teach the ability to deliver a liquid embolic material to effectuate a transient embolization and they include compositions comprising each of the claimed components and they are stable.
Unexpected results that are commensurate in scope with the breadth of the claims have not been shown as compared to the closest prior art.
Status of the Claims
Claims 16-35 are pending and examined.
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.
Claims 16-35 are rejected under 35 U.S.C. 103 as being unpatentable over Sawhney et al., (US2020/0368402) (filed May 8, 2020), in view of Dreher et al., (US2019/0070332), and in view of Caroline et al., (US2016/0346202).
Sawhney teaches using embolic materials to treat hypervascularization formed in response to chronic inflammation in a musculoskeletal vasculature. See Abstract. Osteoarthritis an inflammatory pain in synovial joints is an example of neovascularization that can result from pain. See par. 3. Microspheres have some flow and mechanical property advantages over particles. See par. 19. The method is to transiently block blood flow in a hypervascular inflammatory condition with the embolic material. See par. 25. The area to be treated includes a heel, spine, shoulder, hip, knee, or elbow, e.g. See prior art claim 16. Iodinated contrast medium has been used as well. See par. 22. The embolic material can be delivery through a catheter or through a reservoir of embolic material. See par. 7. The administration can target a vasculature including an artery. See par. 21, 22. The microspheres can ranges from 20 to 100 microns, e.g. See par. 31. Co-delivery can include NSAIDs and other anti-inflammatory agents, e.g. See par. 40.
Sawhney does not describe properties of known embolic compositions.
Dreher teaches therapeutic emulsion embolic compositions wherein an oil component typically includes iodized ethyl-esters of fatty acids of poppy seed oil (i.e., Lipiodol®). See par. 2. The examiner notes that Lipiodol is ethiodized oil, which include non-iodinated ethyl palmitate and ethyl stearate and ethyl monoiodostearet and ethyl diiodostearate thereby including both iodinated and non-iodinated ethyl esters. Even further, the aqueous component typically comprises an iodinated contrast agent to improve visualization during drug delivery. See par. 2. Iodine contrast agents can include iopamidol, iohexol, iodixanol, or iopromide. See par. 55. Absent evidence to the contrary, iodine contrast agents are considered functional equivalents. Iodine containing microspheres formed an emulsion that was stable to form stable droplets. See par. 142. The ratio of oil to aqueous phase includes a ratio of 2:1 up to 5:1. See Table 3 and par. 119. Stable compositions were formed where the ratio of oil to water was at least 2:1. See par. 126. In one example, microspheres were sieved to provide a size range of 70 to 150 μm. This is optimizable and overlaps the claims emulsion droplet size. In addition to a contrast agent, the aqueous phase can comprise an additional drug. See par. 81. The aqueous iodine content ranged from a low of 33 mg/ml to 155 mg/ml. See Figure 4. Figure 10 evaluated different iodine content.
Caroline teaches stable oil in water emulsions that include 20-40% aqueous phase and 60-80% lipid phase wherein the Lipiodol® is used and it includes a mixture of iodized and non-iodized fatty acids of poppyseeds oil. See par. 64. The viscosity of the composition can be 40 to 80 mPa at 37°C. See prior art claim 12 and par. 52. The aqueous phase can comprise the contrast agent and it can be ioversol among others. See par. 43. The iodine concentration of Lipiodol is shown to have an iodine concentration of 480 mg/ml for 37 to 39% w/w. See par. 65.
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985); and 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).
It would have been prima facie obvious to a person having ordinary skill in the art prior to the filing of the instant application to combine the teachings of Sawhney, Dreher, and Caroline to arrive at the claimed methods. One would be motivated to do so because Sawhney teaches using a liquid embolic composition for the claimed purposes, which is a repurposing of liquid embolic compositions, to treat neovascular inflammatory conditions, including osteoarthritis. While Sawhney does not describe an embolic composition with specificity, the prior art recognizes emulsion embolic compositions wherein an oil component “typically” includes iodized ethyl-esters of fatty acids of poppy seed oil and “typically” includes an aqueous component comprising an iodinated contrast agent to improve visualization during delivery. The use of the claimed contrast agents, droplet size, and ratio of oil to water are taught. An oil to water ratio above 2 is preferred to impart stability. The microsphere size and viscosity overlap that taught by the prior art. Further, the iodine concentration in aqueous phase was tested at low and higher levels, which provide a starting point for further optimization. Absent evidence to the contrary deviations in this will not, per se, constitute a patentable distinction. Further, there is no requirement in the prior art that particles and chemotherapeutic agent be incorporated into the composition. While the prior art does use chemotherapeutic agents when treating cancer, this would be an obvious component to avoid using when treating the subject populations described by Sawhney. Even further, if a subject with a condition described by Sawhney is not being treat completely and sufficiently with an oral analgesic or physical therapy, or any other therapy, it would be obvious to try other methods of treatment, including that taught by Sawhney. In view of the combination of prior art as a whole, there is a reasonable and predictable expectation of success in treating chronic inflammatory conditions with embolic agents as described by the cited prior art. A chemotherapeutic agent would not be required in such composition for treating osteoarthritis and the use of claimed components at optimized concentrations would require nothing more than routine experimentation.
As such, no claim is allowed.
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 extension fee 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 JARED D. BARSKY whose telephone number is (571)-272-2795. The examiner can normally be reached on Monday through Friday from 8:30 to 5:30. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Amy L. Clark can be reached on 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JARED BARSKY/Primary Examiner, Art Unit 1628