DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 8/8/24 has been entered.
Claims Status
Claims 1-3 and 5-21 are pending in the application.
Claim Objections
Claim 8 is objected to because of the following informalities: the instant claim 8 recites “claim-“ but does not recite the claim to which it depends. Appropriate correction is required.
Claim 16 is objected to because of the following informalities: the instant claim 16 recites “claim 2-wherein“ that is believed to be a typographical error. Appropriate correction is required.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim 1-3 and 5-21 is/are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Kawabata et al. (US 2008/0311046A1) in view of Zhang et al. (Ultrasound in Med & Biol., Vol. 36, No. 10, pp1691-1703, 2010) and Kripfgans et al. (IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control, Vol. 52, No. 7, July 2005, p1101-1110).
Kawabata et al. (US 2008/0311046A1) discloses ultrasound contrast agents used for the method of diagnosis, such as ultrasonography (p2, [0024]; claim 14) that encompasses the method of medical diagnostic imaging of the instant claims.
With regards to the instant claims 2, Kawabata et al. further discloses that the ultrasound contrast agents may be used for the method of therapy (p2, [0025]; p5, [0056]; p6, [0081]) that encompasses the method of medical therapy of the instant claims.
The ultrasound contrast agents comprise at least one kind of low-boiling water-insoluble liquid substance (with a boiling point lower than 37°C) and a least one high-boiling water-insoluble substance (with a boiling point higher than 37°C) (abstract; p2, [0021]).
The low-boiling water-insoluble liquid substance is any one of straight-chain hydrocarbons, branched-chain hydrocarbons, straight-chain halogenated hydrocarbons and branched-chain halogenated hydrocarbons (p2, [0023], p3, [0034]) that encompasses the fluorocarbon, perfluorocarbon, chlorofluorocarbon, hydrofluorocarbon and hydrocarbon of the instant claims.
The low-boiling water-insoluble liquid substance comprise decafluorobutane (DFB) having a
boiling point of 4°C under normal pressure (FIG. 2; p3, [0032]).
The DFB encompasses the liquid component having a boiling point that is below room temperature (25°C) at atmospheric pressure of the instant claims and the DFB of the instant claims 5 and 13.
The ultrasound contrast agent comprises a water-soluble polymer (e.g. mPEG-2000-PE) or a surfactant (e.g. lecithin) to enclose the emulsion of a low-boiling water-insoluble liquid substance and a least one high-boiling water-insoluble substance (p3, [0038],[0040]; Example 4) that encompasses providing encapsulated droplets, each encapsulated droplet comprising a liquid encapsulated in a shell
of the instant claims.
The mPEG-2000-PE encompasses the shell polymer of the instant claims 6 and 14 and the lecithin encompasses a shell lung surfactant of the instant claims.
The ultrasound contrast agent is injected into a vein of a living body wherein the ultrasound contrast agent is a liquid at the time of injection (p6, [0069]; claim 14) that encompasses introducing the liquid encapsulated droplets into a tissue to be imaged of the instant claims.
The ultrasound contrast agent is in the form of an encapsulated liquid which is evaporated by application of ultrasonic energy wherein the low-boiling water-insoluble liquid substance vaporizes upon the application of ultrasound to yield a gas that increases the size and results in a bubble of encapsulated gas (abstract; FIG. 1; p2-3, [0021],[0029]).
The application of ultrasonic energy, the conversion of a liquid phase to a gas phase and formation of a bubble of encapsulated gas encompasses providing activation energy to cause the liquid within the encapsulated droplet to change from a liquid phase to a gas phase, causing the encapsulated droplet to increase in size and become bubbles of encapsulated gas of the instant claims.
The ultrasound contrast agent gives an image upon application of ultrasound (claim 1) that encompasses performing ultrasonic imaging of the instant claims.
The ultrasound contrast agent may comprise a molecular probe chemically or physically attached thereto, such as antibodies, proteins, peptides, etc. (p3, [0039]) that encompasses the component that causes the shell to attach to cells of a tissue within a target region, targets a specific component within a cell and promotes intracellular uptake of the instant claims 10-12 and 18-20.
With regards to the instant claim 3, Kawabata et al. further discloses that the peptides and
antibodies are preferred for the diagnosis of tumors (p3, [0039]) that encompasses the tumor,
cancerous cells, etc. of the instant claim 3.
The high-boiling water-insoluble substance is evaporated not by the energy of applied ultrasound but by the energy of ultrasound accumulated in bubbles (or vapor) originating from the low-boiling water-insoluble substance (p3, [0029]) that encompasses the liquid comprises a mixture of a plurality of different perfluorocarbons and each having a different activation energy of the instant claims.
The low-boiling water-insoluble substance (which is a liquid) vaporizes to give a mixed phase of liquid and gas. The gas evolved is more dilute than that which is evolved from an ultrasound contrast agent composed of a single substance because of interactions between the gas and the high-boiling water-insoluble substance surrounding it. This results in discrete microbubbles that make their surrounding substance increase in the apparent absorption factor of ultrasonic energy that encompasses the activation energy is adjustable based on the relative proportions of the plurality of different perfluorocarbons of the instant claims 9 and 17.
With regards to the instant claims 7 and 15, Kawabata et al. does not explicitly disclose a stabilized bilayer and multilayer folds.
The lecithin, proteins, peptides, etc. encompass the lung surfactants, proteins and peptides of the instant claims, have the same properties and are capable of the same functions, such as being components to form and stabilize bilayer and multilayer folds of the shell.
With regards to the instant claim 2, Kawabata et al. does not disclose bubbles obstruct the flow
of blood within the target region.
Zhang et al. (Ultrasound in Med & Biol., Vol. 36, No. 10, pp1691-1703, 2010) discloses fluoropentane droplets encased in lipids that are used for targeted tissue occlusion (abstract; p1692, left column, first full paragraph; p1692, Perfloropentane droplet preparation).
Microbubbles are generated by phase conversion of the perfluoropentane within renal arteries or segmental arteries (abstract).
Acoustic droplet vaporization (ADV) uses ultrasound to induce phase transition of liquid droplets that are near their boiling point or are superheated in vivo (p1692, left column, first full paragraph). The droplet phase-transition and expand into gas bubbles approximately 4-5 times larger in diameter than the droplets and can occlude capillaries and small arterioles (p1692, left column, first full paragraph).
At the time of the invention it would have been obvious to one of ordinary skill in the art to
utilize the ultrasound contrast agents of Kawabata et al. for occlusion during tumor therapy to allow for
the advantage of a combination of imaging a tumor site, heat therapy and reducing tumor size via blocking blood flow.
With regards to the instant claim 21, Kawabata et al. does not disclose a therapeutic agent enters into cells via vaporization.
Zhang et al. discloses that ADV uses ultrasound to induce phase transition as well as that stated above.
Zhang et al. further discloses that the ultrasonically phase-transitioned perfluorocarbon droplets have been investigated for drug delivery (p1692, left column, first full paragraph).
Kripfgans et al. (IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control, Vol. 52, No. 7, July 2005, p1101-1110) discloses that vascular occlusion can be used for a variety of cancer types. Perfluorocarbon-based emulsions can be made to carry and, upon vaporization, locally deposit chemotherapy drugs. It is beneficial to use local deposition of chemotherapeutic agents directly inside of the tumor’s vasculature because the nature of cancer blood vessels (p1108, C. Prospects of Cancer Treatment).
At the time of the invention it would have been obvious to one of ordinary skill in the art to utilize the ultrasound contrast agents of Kawabata et al. for delivery of therapeutic agents to a tumor via ADV for the advantage of treating various cancer types via site specific targeting and delivery of the chemotherapeutic agents.
With regards to the instant claims 1,2,8 and 16, Kawabata et al. does not disclose that each liquid component has a boiling point below room temperature at atmospheric pressure or a single perfluorocarbon having a single activation energy.
Zhang et al. further discloses that ADV occurs with liquid droplet comprising a single perfluorocarbon (PCF) (abstract; (p1692, left column, first full paragraph).
At the time of the invention it would have been obvious to one of ordinary skill in the art to utilize the ultrasound contrast agents of Kawabata et al. with a single perfluorocarbon, such as one having a boiling point below room temperature at atmospheric pressure and having a single activation energy as Zhang et al. teaches that the ADV uses ultrasound to induce phase transition of liquid droplets
comprising a single PCF with a single activation energy to expand into gas bubbles approximately 4-5 times larger in diameter that are advantageous for occlusion treatment techniques.
The references of Kawabata et al. and Zhang et al. are drawn to analogous methods of using liquid perfluorocarbon droplets to yield expanded gas bubbles for tumor therapy via the administration of ultrasound. Therefore, it would have been predictable to examine a combination of liquid perfluorocarbons or a single perfluorocarbon, such as multiple or one perfluorocarbon having a boiling point(s) below room temperature at atmospheric pressure to determine the most effective liquid perfluorocarbon(s) droplet formulation for individual or a combination of the methods imaging,
therapeutic agent delivery via ADV and/or occlusion.
Response to Arguments
Applicant's arguments filed 6/25/24 have been fully considered but they are not persuasive.
Applicant asserts that Kawabata is directed to the use of an ultrasound contrast agent comprising at least one low-boiling point water-insoluble substance with a boiling point lower than 37°C at normal pressure and at least one high-boiling point water-insoluble substance with a boiling point higher than 37°C at normal pressure. Kawabata does not disclose an agent in which all of the components in the liquid have a boiling point that is below room temperature (25°C) at atmospheric pressure.
The reference of Kawabata was not used to teach of each components in the liquid have a boiling point that is below room temperature (25°C) at atmospheric pressure but was used to teach that stated above.
The reference of Zhang was used to teach that stated above and further discloses that ADV occurs with liquid droplet comprising a single perfluorocarbon (PCF).
At the time of the invention it would have been obvious to one of ordinary skill in the art to utilize the ultrasound contrast agents of Kawabata et al. with a single perfluorocarbon, such as one having a boiling point below room temperature at atmospheric pressure and having a single activation energy as Zhang et al. teaches that the ADV uses ultrasound to induce phase transition of liquid droplets
comprising a single PCF to expand into gas bubbles approximately 4-5 times larger in diameter that are
advantageous for occlusion treatment techniques.
The references of Kawabata et al. and Zhang et al. are drawn to analogous methods of using liquid perfluorocarbon droplets to yield expanded gas bubbles for tumor therapy via the administration of ultrasound. Therefore, it would have been predictable to examine a combination of liquid perfluorocarbons or a single perfluorocarbon, such as multiple or one perfluorocarbon having a boiling point(s) below room temperature at atmospheric pressure to determine the most effective liquid perfluorocarbon(s) droplet formulation for individual or a combination of the methods imaging, therapeutic agent delivery via ADV and/or occlusion.
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.
Claims 1-3 and 5-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 and 8-16 of U.S. Patent No. 11,1233,302B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the particle U.S. Patent No. 11,1233,302B2 comprising a first substance that consists of at least one perfluorocarbon having a boiling point below 25°C at atmospheric pressure (e.g. DFB or OFP) and a different second substance which is liquid at 25°C and atmospheric pressure encompasses the liquid perfluorocarbon components having a boiling point below 25°C at atmospheric pressure (e.g. DFB or OFP) of the instant claims.
The at least one perfluorocarbon having a boiling point below 25°C at atmospheric pressure (e.g. DFB or OFP) of U.S. Patent No. 11,1233,302B2 encompasses the single perfluorocarbon having a single activation energy of the instant claims.
The second substance of U.S. Patent No. 11,1233,302B2 comprises at least one lipid, protein,
polymer, gel, surfactant, peptide or sugar that encompasses the at least one lipid, protein, polymer, gel, surfactant, peptide or sugar of the instant claims and the shell of the instant claims.
The second substance of U.S. Patent No. 11,1233,302B2 comprises lung surfactants,
amphiphiles, proteins, or their peptide components to form and stabilize bilayers and multilayer folds of
the encapsulated material that encompasses the lung surfactants, amphiphiles, proteins, or their peptide components to form and stabilize bilayers and multilayer folds of the shell of the instant claims.
The at least one perfluorocarbon comprising a mixture of a plurality of different perfluorocarbons and each having a different activation energy, wherein an activation energy of the particle is adjustable based on the relative proportions of the plurality of different perfluorocarbons of U.S. Patent No. 11,1233,302B2 encompasses the liquid mixture of a plurality of different perfluorocarbons and each having a different activation energy, wherein an activation energy of the particle is adjustable based on the relative proportions of the plurality of different perfluorocarbons of the instant claims.
The component that causes the second substance to attach to cells of a tissue within a target region, attaches to proteins expressed by the cells, such as tumor, cancerous cells or pre-cancerous cells and promotes intracellular uptake of U.S. Patent No. 11,1233,302B2 encompasses the shell component that causes the shell to attach to cells of a tissue within a target region, such as tumor, cancerous cells or pre-cancerous cells and promotes intracellular uptake of the instant claims.
The particles of U.S. Patent No. 11,1233,302B2 comprise a therapeutic agent: a drug to be delivered to a target region that encompasses the therapeutic agent that enter the cells of a target region of the instant claims.
The particles of U.S. Patent No. 11,1233,302B2 encompasses the activatable droplets of the instant claims as they comprise analogous components and therefore are capable of the same functions and have the same properties, such as being used for a method of medical diagnostic imaging and a method for medical therapy for delivery a therapeutic agents into cells via sonoporation, vaporization, endocytosis or contact-facilitated diffusion.
Conclusion
No claims are allowed at this time.
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/MELISSA J PERREIRA/Examiner, Art Unit 1618