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 .
Receipt is acknowledged of Applicant’s Amendment filed on 03/24/2026.
Claims 43, 45-48 have been amended.
Claims 44, 54-55 have been canceled.
Claims 43, 45-53 are pending in the instant application.
Note, rejections and objections not reiterated from previous office actions are hereby withdrawn. The following rejections or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Note, Applicant’s Terminal Disclaimer in re Application 17/6126,166 filed on 03/24/2026 was disapprove.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim 43, 45-53 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over copending Application No. 17/616,166 (reference application).
The co-application recites a method for disrupting or destroying vascular thromboses or plaques, comprising: administering to a subject in need thereof an aqueous emulsion or suspension of claim 1; and applying ultrasound to a targeted region of an organ of the subject having vascular thromboses or plaques thereby destroying or reducing the vascular thromboses or plaques (see claim 36). An aqueous emulsion or suspension of microbubbles and/or nanodroplets having one or more fibrin-binding ligands attached thereto (see claim 1), wherein the fluorinated gas comprises octafluoropropane (see claim 11).
The difference between instant application and the patented claims is that the patent claims include additional limitations. Thus, the invention of the patent is in effect a “species” of the “generic” invention of the application claims. It has been held that the generic invention is “anticipated” by the “species”, and, therefore, the application claims are not patentably distinct from the claims of the patent and are rejected on the ground of nonstatutory obviousness-type double patenting. See In re Goodman, 29 USPQ2d 2010 (Fed. Cir. 1993).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Note, Applicant’s Terminal Disclaimer in re Application 17/6126,166 filed on 03/24/2026 was disapprove.
Claims 43, 45-53 are rejected on the ground of nonstatutory double patenting as being unpatentable over U.S. Patent No. 6,576,220 in view of SWENSON et al (US 8,293,214)
The patent recites a non-invasive method for performing surgery in the vasculature of a patient, said method comprising: (a) administering intravascularly to said patient a composition comprising, in an aqueous diluent, vesicles comprising a gas or gaseous precursor and a stabilizing compound; and (b) applying ultrasound to said patient in an amount sufficient to induce activation or rupture of said vesicles (see claim 1), wherein said surgery alleviates a thrombosis in said patient (see claim 6), wherein said fluorinated compound is perfluoropropane (see claim 13), wherein the vesicles have a mean diameter less than about 12 microns (see claim 40).
The patent does not recite the lower size limit of the vesicles, such as nano-size; however, the patent’s specification discloses “the vesicles can be appreciably under a micron, even under 100 nm diameter”.
SWENSEN teaches the prior art had known of a method of ultrasound imaging (see claim 22), such as thrombus in the abdominal artery (see col. 104, Example 68), which reads on vascular thrombosis, comprised of: (a) administering a composition comprising gas-filled microvesicles to a patient (see claim 22); and (b) subjecting said patient to ultrasound irradiation (see claim 22), wherein the preferred gas is fluorinated (see col. 22, line 39), such as perfluoropropane (see col. 22, line 57-58), which is also known as octafluoropropane and would be acoustically activable. Additional disclosures include: “The term "gas-filled microvesicles" includes any structure comprising bubbles of gas of micronic or nanometric size surrounded by an envelope or layer (including film-form layers) of a stabilizing material” (see col. 3, line 62-65). Any biocompatible gas, gas precursor or mixture thereof may be employed to fill the above microvesicles (see col. 22, line 20-21). Gaseous precursors… undergo a liquid/gas phase transition and are converted to a gas within the human body (see 34-36), which reads on droplets.
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate micro and/or nano-sized gas precursor droplets. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because micro and/or nano-sized gas precursor droplets are well-known in this field of the art in the prior art.
Claim Rejections - 35 USC § 102
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 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(s) 43, 45-46, 48-51, 53 is/are rejected under 35 U.S.C. 102(a)(10 as being anticipated by SWENSON et al (US 8,293,214).
SWENSON teaches a method of ultrasound imaging (see claim 22), such as thrombus in the abdominal artery (see col. 104, Example 68), which reads on vascular thrombosis, comprised of: (a) administering a composition comprising gas-filled microvesicles to a patient (see claim 22); and (b) subjecting said patient to ultrasound irradiation (see claim 22), wherein the preferred gas is fluorinated (see col. 22, line 39), such as perfluoropropane (see col. 22, line 57-58), which is also known as octafluoropropane and would be acoustically activable. Additional disclosures include: “The term "gas-filled microvesicles" includes any structure comprising bubbles of gas of micronic or nanometric size surrounded by an envelope or layer (including film-form layers) of a stabilizing material” (see col. 3, line 62-65). Any biocompatible gas, gas precursor or mixture thereof may be employed to fill the above microvesicles (see col. 22, line 20-21). Gaseous precursors… undergo a liquid/gas phase transition and are converted to a gas within the human body (see 34-36), which reads on droplets.
SWENSON teaches further teaches “class of contrast agents, particularly useful for ultrasound contrast imaging, includes suspensions of gas bubbles of nano- and/or micro-metric size dispersed in an aqueous medium. Of particular interest are those formulations where the gas bubbles are stabilized, for example by using emulsifiers, oils, thickeners or sugars, or by entrapping or encapsulating the gas or a precursor thereof in a variety of systems. These stabilized gas bubbles are generally referred to in the art with various terminologies, such as, for instance, "microvesicles", "microspheres", "microbubbles", "microcapsules" or "microballoons" (see col. 1, line 35-50); sugars, such as trehalose (see col. 19, line 24), which reads on stabilizing agent; PEG-4000 (see col. 97, line 10-15); aqueous suspension (see col. 4, line 13-15); targeting ligands (see abstract), such as fibrin-targeting (see col. 12, line 35-50), preferably comprising about 10 amino acids (see col. 12, line 66-67).
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.
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.
Claim(s) 43, 45-53 is/are rejected under 35 U.S.C. 103 as being unpatentable over SWENSON et al (US 8,293,214) in view of OLIVEIRA et al (Peptide-Based Fibrin-Targeting Probes for Thrombus Imaging. Dalton Trans. 2017 October 31; 46(42): 14488–14508).
As discussed above, SWENSON teaches a method of ultrasound imaging (see claim 22), such as thrombus in the abdominal artery (see col. 104, Example 68), which reads on vascular thrombosis, comprised of: (a) administering a composition comprising gas-filled microvesicles to a patient (see claim 22); and (b) subjecting said patient to ultrasound irradiation (see claim 22), wherein the preferred gas is fluorinated (see col. 22, line 39), such as perfluoropropane (see col. 22, line 57-58), which is also known as octafluoropropane and would be acoustically activable. Additional disclosures include: “The term "gas-filled microvesicles" includes any structure comprising bubbles of gas of micronic or nanometric size surrounded by an envelope or layer (including film-form layers) of a stabilizing material” (see col. 3, line 62-65). Any biocompatible gas, gas precursor or mixture thereof may be employed to fill the above microvesicles (see col. 22, line 20-21). Gaseous precursors… undergo a liquid/gas phase transition and are converted to a gas within the human body (see 34-36), which reads on droplets.
SWENSON teaches further teaches “class of contrast agents, particularly useful for ultrasound contrast imaging, includes suspensions of gas bubbles of nano- and/or micro-metric size dispersed in an aqueous medium. Of particular interest are those formulations where the gas bubbles are stabilized, for example by using emulsifiers, oils, thickeners or sugars, or by entrapping or encapsulating the gas or a precursor thereof in a variety of systems. These stabilized gas bubbles are generally referred to in the art with various terminologies, such as, for instance, "microvesicles", "microspheres", "microbubbles", "microcapsules" or "microballoons" (see col. 1, line 35-50); sugars, such as trehalose (see col. 19, line 24), which reads on stabilizing agent; PEG-4000 (see col. 97, line 10-15); aqueous suspension (see col. 4, line 13-15); targeting ligands (see abstract), such as fibrin-targeting (see col. 12, line 35-50), preferably comprising about 10 amino acids (see col. 12, line 66-67).
SWENSON does not teach using specific fibrin-binding peptides selected from Table 1, such as Tn6.
OLIVEIRA teaches the prior art had known of peptide-based fibrin-targeted probes for molecular imaging of thrombosis (see title and abstract), such as Tn6, Tn7 and Tn10 (see pg. 26 at Figure 3), which has about 11-16 amino acids (see pg. 45 at Table 1).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate using specific fibrin-binding peptides selected from Table 1, which are Tn6, Tn7 and Tn10. The person of ordinary skill in the art would have been motivated to make those modifications, because these peptides would allow specific targeting of thrombosis, and reasonably would have expected success because the primary reference teaches using fibrin binding peptides to target thrombosis.
The references do not specifically teach the nanoparticle size range as claimed by Applicant. The nanodroplet size of a nano-composition is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the nanodroplet/particle size in order to best achieve the desired results, such as the small size needed to travel through the vasculature system. Thus, absent some demonstration of unexpected results from the claimed parameters, this optimization of nanodroplet/particle size would have been obvious at the time of Applicant's invention.
Response to Arguments
Applicant argues that firstly, the method of amended claim 43 in an initial step administers acoustically activatable nanodroplets with a fluorinated gas in a condensed phase, i.e, fluorinated liquid core nanodroplets. In contrast, Swenson discloses administering initially gas-filled stabilized microvesicles, including microbubbles, microspheres, microcapsules, and microballoons. Secondly, in the method of amended claim 43, the nanodroplets with the fluorinated condensed gas phase therein do not contain gas until they undergo acoustic droplet vaporization (ADV) in situ under therapeutic ultrasound pressures ([0032-0033]). In contrast, in Swenson, gas-filled microvesicles are the only composition administered and subjected to ultrasound vaporization at the targeted site.
The Examiner finds this argument unpersuasive, because SWENSON teaches any biocompatible gas, gas precursor or mixture thereof may be employed to fill the above microvesicles (see col. 22, line 20-21). Gaseous precursors… undergo a liquid/gas phase transition and are converted to a gas within the human body (see 34-36), which reads on droplets.
Applicant argues that firstly, regarding specific fibrin-binding peptides, at best, arguendo, should a suggestion be found in Oliveira to modify Swenson with any of the Tn6, Tn7 or Tn10 peptides disclosed in Oliveira, the suggestion might be to modify the microvesicles for ultrasound imaging. However, Applicant submits that, although fibrin-binding peptides may be known in the art, the references in the combination must be considered as a whole. As such Swenson discloses gas-filled microvesicles that may be modified with targeting ligands, such as fibrin-targeting with any of nine peptide sequences (Table 1; col. 12, line 35-50) for thrombus imaging via ultrasound. As a whole, Oliveira in the combination discloses that phage-derived peptides from Tn6, Tn7 and Tn10 libraries bound to fibrin. However, the intent of Oliveira is directed to fibrin-targeting probes for MRI, PET, SPECT and optical imaging where the reference discloses Gd-DTPA modified Tn6 and Tn7 chelates as MRI probes for thrombus detection (pages 14493-14494). As it is known in the art that the paramagnetic/superparamagnetic fibrin-targeting contrast agents for MRI, such as the gadolinium-DTPA in Oliveira, are fundamentally different from the microvesicles comprising a fibrin-targeting agent used for ultrasound imaging in Swenson. Thus, Applicants submit that a reasonable expectation of success is not found in modifying the microvesicles in Swenson with the phage-derived, Gd-DTPA chelated Tn6 or Tn7 peptides in Oliveira, particularly as this secondary reference is completely silent about ultrasound imaging.
The Examiner finds this argument unpersuasive, because 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). In this instance OLIVEIRA is a secondary reference to show that the prior art had known of peptide-based fibrin-targeted probes for molecular imaging of thrombosis (see title and abstract), such as Tn6, Tn7 and Tn10 (see pg. 26 at Figure 3), which has about 11-16 amino acids (see pg. 45 at Table 1). It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate using specific fibrin-binding peptides selected from Table 1, which are Tn6, Tn7 and Tn10. The person of ordinary skill in the art would have been motivated to make those modifications, because these peptides would allow specific targeting of thrombosis, and reasonably would have expected success because the primary reference teaches using fibrin binding peptides to target thrombosis
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.
Telephonic Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAKE MINH VU whose telephone number is (571)272-8148. The examiner can normally be reached Mon-Fri 9:00am-5:30pm.
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/JAKE M VU/Primary Examiner, Art Unit 1618
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