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 .
Summary
Claims 1-15 are pending in this office action. All pending claims are under examination in this application.
Priority
The current application was filed on December 21, 2023 is a 371 of PCT/EP2021/066751 filed June 21, 2021.
Information Disclosure Statement
Receipt of the Information Disclosure Statement filed on December 21, 2023 is acknowledged. A signed copy of the document is attached to this office action.
Claim Objections
Claims 1-15 are objected to because of the following informalities:
Claim 1 should have the article “a” prior to “composition.”
Dependent claims 2-15 fail to cure the defect of claim 1.
Claims 2-8 should have the article “the” prior to “composition.”
Claim 9 should have the article “a” prior to “wound.”
Claim 10 should have the article “a” prior to “method.” Furthermore, claim 10 should have the article “the” prior to “wound.”
Dependent claims 11-14 fails to cure the defects of claim 10.
Claims 11-14 should have the article “the” prior to “method.”
Additionally, claims 8 and 12-13 should be consistent with claim 11, and have the necessary description for the stated value when first mentioned (MPa or %). For example, claim 8 states, “between about 1 and about 8 MPa.” This should be written, “between about 1 MPa and about 8 MPa.”
Appropriate correction is required.
Objections to the Drawings
New corrected drawings in compliance with 37 CFR 1.121(d) are required in this application because Figure 1 is missing text descriptions within the boxes. Applicant is advised to employ the services of a competent patent draftsperson outside the Office, as the U.S. Patent and Trademark Office no longer prepares new drawings. The corrected drawings are required in reply to the Office action to avoid abandonment of the application. The requirement for corrected drawings will not be held in abeyance.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 8 and 12-13 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claims 8 and 12-13 the phrase "more preferably" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 15 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. Claim 15 is written as a “use” claim and does not recite process steps. Additionally, claim 15 does not comply with the four statutory categories. It is therefore, indefinite.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 15 is directed to non-statutory subject matter. The claim 15 does not fall within at least one of the four categories of patent eligible subject matter because it is written as a “use” claim.
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.
Claims 1, 3-4, and 10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kohane et al. (US2013/0041311A1).
Kohane et al. is considered the closest prior art as it teaches methods, devices, and systems for on-demand ultrasound-triggered drug delivery (see title). Furthermore, Kohane et al. disclose injectable or implantable drug delivery systems providing on-demand ultrasound-triggered drug release and methods for controlling the release of drug in a patient are provided herein. The on-demand drug delivery systems contain a drug depot, and a drug encapsulated in an encapsulating material, where the encapsulating material is different from the depot. In the preferred embodiment, the depot also contains microbubbles that encapsulate one or more gases. The
microbubbles enhance the drug release when ultrasound is applied compared to the same system in the absence of microbubbles. In a preferred embodiment, the drug delivery system, contains an encapsulating material, preferably liposomes,
a drug to be delivered, microbubbles, and at least two hydrogel-forming precursor components. Following injection or implantation, the patient can control the time, location and dosage released by administering ultrasound (see abstract).
Regarding instant claim 1, Kohane et al. teach a composition comprising a matrix and a carrier encapsulating a therapeutic compound. The necessary citations of Kohane et al. that pertain to instant claim 1 are presented in Table I.
Table I
Instant Claim 1
Kohane et al. Citations
A composition comprising a matrix and a carrier encapsulating a therapeutic compound,
Kohane et al. discloses a drug delivery system which is an injectable, multi-component system for providing on-demand, ultrasound-triggered drug release, containing an encapsulating material, preferably liposomes, microbubbles and a hydrogel (see title and abstract).
In use, the liposomes carry the drugs and prevent their premature release. The hydrogel can be an alginate (see paragraph [0035]). Alginate can be ionically cross-linked with divalent cations, in water, at room temperature, to form a hydrogel matrix (see paragraph [0038]). The preferred cations for cross-linking of the polymers with acidic side groups to form a hydrogel are divalent and trivalent cations such as copper, calcium, aluminum, magnesium, strontium, barium (see paragraph [0044]). The overall charge for the liposome may be neutral, positive or negative. Preferably the overall charge for the liposome is neutral or the same as the charge of the drug to be encapsulated, if the drug has an overall charge (see paragraph [0069]). A long list of drugs to be delivered is disclosed (see paragraphs [0120-0149]). Liposomes were prepared according to the method (see paragraph [0180]) by modified thin lipid film hydration: DSPC:DSPG:cholesterol, negatively charged, DSPC:DODAB:cholesterol, positively charged, (molar ratio 3:1:2) and DSPC:cholesterol, neutral, (molar ratio 4:2). DextranCHO/CMC-ADH hydrogel was prepared according to the method disclosed (see paragraphs [0192-0197]).
wherein the matrix is configured to release the therapeutic compound under an ultrasound stimulus.
The microbubbles enhance the drug-release and the hydrogel maintains both the encapsulating materials and the microbubbles in close proximity to each other and in a relatively constrained location so that they can affect release when ultrasound is applied (see Figure 1; also see paragraph [0009]). The encapsulating material will open up, thereby releasing the drug into the drug depot, which will erode and/or have pores with larger openings following ultrasound application. Then the drug depot will stop releasing drug when the ultrasound pulse is stopped (see paragraph [0167]).
Regarding instant claims 3-4 and 10, Kohane et al. teach wherein the matrix comprises an alginate hydrogel comprising the therapeutic compound, the alginate hydrogel being configured to release the therapeutic compound under an ultrasound stimulus. Please see the discussion and citation within instant claim 1. This would apply directly to a method for activating the drug release of the composition described within Table I.
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.
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 non-obviousness.
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.
Claims 1-2 and 4-15 are rejected under 35 U.S.C. 103 as being unpatentable over Kohane et al. in view of Villanueva et al. (WO2021/097224A1, published in May 2021), Mooney et al. (WO2016/161372A1), and Hunt et al. (US2020/0353292A1, published in November 2020).
[The Examiner is going to introduce each new reference and then combine them where appropriate to reject the instant claims.]
1. Villanueva et al.
Villanueva et al. teach cardioprotective microbubble-liposomal drug complexes (see title). In addition, Villanueva et al. disclose that the presently described drug-loaded liposomal conjugated to polymer microbubbles showed: i) increased tumor drug concentration; ii) reduced tumor growth; and ii) increased survival time in a mouse cancer model when exposed to concurrent high and low acoustic pressure ultrasonic pulses as compared to individual high or low acoustic pressure ultrasonic pulses. Notably, when unconjugated drug-loaded liposome were administered with free microbubbles and exposed to concurrent high and low acoustic pressure ultrasonic pulses, a superior tumor growth inhibition was also seen. Three weeks after treatments, DoxLPX+US group showed significantly better left ventricular function indices from echocardiography imaging than the free Dox group. Clinical methods using these liposomal conjugated microbubbles permit an increased therapeutic drug delivery and improved safety profile, respectively due to enhanced, preferential drug accumulation in target tumor tissue and simultaneously reduced drug delivery to non-target tissue (see abstract).
2. Mooney et al.
Mooney et al. teach immunoconjugates for programming or reprogramming of cells (see title). In addition, Mooney et al. disclose that the conjugate compositions and methods are useful to elicit/augment an immune response to a tumor or microbial infection or to reduce the severity of autoimmunity, chronic inflammation, allergy, asthma, periodontal disease, and transplant rejection (see abstract).
3. Hunt et al.
Hunt et al. teach automatically steering and focusing therapeutic ultrasound systems (see title). In addition, Hunt et al. disclose a system for therapeutic ultrasound includes one or more ultrasound transducer modules that are configured to generate ultrasound waves at a first power level and at a second power level, the first and second power levels being different and the second power level being sufficient to provide a therapeutic effect for a living subject, and an electronic controller in communication with the one or more ultrasound transducer modules, the electronic controller being programmed to cause the one or more ultrasound transducer modules to generate a first ultrasound wave at the first power level and detect a reflected ultrasound wave from the subject in response to the first ultrasound wave, determine a location of a target within the subject based on the detected reflected ultrasound wave, and, after determining the location of the target, generate a second ultrasound wave at the second power level focused at the target (see abstract).
The teachings of Kohane et al. are disclosed above within the 35 U.S.C. §102 Section. Additionally, the following claims are taught by Kohane et al. within the 35 U.S.C. §103 Section.
Regarding instant claim 5, Kohane et al. teach wherein the alginate hydrogel is selected from the group comprising calcium alginate, magnesium alginate, strontium alginate and barium alginate hydrogel. Kohane et al. disclose polysaccharides can also be cross-linked to form a water-insoluble network. For many polysaccharides, this can
be accomplished by reaction with calcium salts or multivalent cations which cross-link the main polymer chains. Pectin, alginate, dextran, amylase and guar gum are subject to crosslinking in the presence of multivalent cations. Complexes between oppositely charged polysaccharides can also be formed; pectin and chitosan, for example, can be complexed via electrostatic interactions (see paragraph [0085] within Kohane et al.). Therefore, a skilled artisan (POSITA; person having ordinary skill in the art) would use this disclosure and purchase the commercially available calcium alginate.
Regarding instant claim 6, Kohane et al teach wherein the therapeutic compound is a neutrally charged compound. Kohane et al. disclose one or more drugs, i .e. pharmaceutically active agents, are encapsulated in the encapsulating material. Suitable classes of active agents include, but are not limited to, antibiotic agents, antimicrobial agents, anti-acne agents, antibacterial agents, antifungal agents, antiviral agents, steroidal anti-inflammatory agents, non-steroidal anti-inflammatory agents, anesthetic agents, antipruriginous agents, antiprotozoal agents, anti-oxidants, antihistamines, vitamins, and hormones (see paragraph [0121] within Kohane et al.). A skilled artisan (POSITA) would select a neutrally charged compound from this extensive list of drugs.
Combination of Kohane et al. and Mooney et al.
Regarding instant claim 2, Kohane et al. and Mooney et al. teach wherein the matrix forms a net having a pore size comprised between about 1 nm to about 15 nm. Mooney et al. disclose the pore size is less than about 10 nm…(see page 92, paragraph 4 within Mooney et al.).
Mooney et al. disclose the use of an alginate hydrogel (see page 15, paragraph 2 within Mooney et al.). Furthermore, Mooney et al. disclose the timed pDNA release with ultrasound (see page 28, paragraph 1 within Mooney et al.).
Therefore, a skilled artisan (POSITA) would combine the teachings of Kohane et al. and Mooney et al. under routine experimental conditions due to the disclosed overlap in the two references.
Regarding instant claims 9 and 15, Kohane et al. and Mooney et al. teach a wound dressing comprising a composition according to instant claim 1. Mooney et al. disclose that the compositions and methods are also useful in wound healing, e.g., to treat smoldering wounds (slow healing), thereby altering the immune system toward healing and resolution of the wound. [The Examiner is relying on the fact that smoldering wounds are a form of chronic wounds (see PTO-892 NPL U).].
Combination of Kohane et al. and Villanueva et al.
Regarding instant claims 7 and 11, Kohane et al. and Villanueva et al. teach wherein the ultrasound stimulus is ranging from about 0.5 MHz to about 15 MHz. Villanueva et al. disclose the combined ultrasound wave has a frequency selected from the group consisting of 0.5 MHz to 1.0 MHZ, 0.75 MHz to 1.25 MHz, 0.9 MHz to 1.1 MHz, 1.0 MHz to 10.0 MHz, and 1.0 MHz (see pages 2 and 3, lines (2) 30-31 (3) 1 within Villanueva et al.).
Villanueva et al. disclose the release of a therapeutic agent encapsulated by liposomes conjugated to polymer microbubbles and released by ultrasound (see page 11, lines 21-31 and page 12, lines 1-14 within Villanueva et al.).
Regarding instant claims 8 and 12, Kohane et al. and Villanueva et al. teach wherein the peak-to-peak acoustic pressure of the ultrasound stimulus is comprised between about 1 and about 8 MPa. Villanueva et al. disclose the US (ultrasound) pulse is a high acoustic pressure US (ultrasound) pulse (~1 MPa) (see page 20, line 10 within Villanueva et al.).
Regarding instant claim 13, Kohane et al. and Villanueva et al. teach wherein the duty cycle of ultrasound is comprised between about 1 and about 25%. Villanueva et al. disclose that the overall duty cycle was 10% (see page 37, line 10 within Villanueva et al.).
Combination of Kohane et al. and Hunt et al.
Regarding instant claim 14, Kohane et al. and Hunt et al. wherein the ultrasound beam is an unfocused ultrasound beam. Hunt et al. disclose the use of an unfocused ultrasound beam.
Hunt et al. disclose the use of a therapeutic ultrasound machine (see claims 1-20 within Hunt et al.). The use of a focused and unfocused ultrasound beam would allow a skilled artisan (POSITA) to expand the ultrasound therapy available for a subject.
Analogous Art
The Kohane et al., Villanueva et al., Mooney et al., and Hunt et al. references are directed to the same field of endeavor as the instant claims, that is, a composition comprising a matrix and a carrier encapsulating a therapeutic compound, wherein the matrix is configured to release the therapeutic compound under an ultrasound stimulus.
Obviousness
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the ultrasound-triggered drug delivery system disclosed by Kohane et al. using the teachings of Villanueva et al., Mooney et al., and Hunt et al. to incorporate the necessary claim limitations.
The Kohane et al., Villanueva et al., Mooney et al., and Hunt et al. references all have considerable overlap with the use of ultrasound to coordinate the release of a therapeutic agent. Therefore, a skilled artisan (POSITA) would be motivated to consult these citations.
Starting with Kohane et al., the skilled person only had to try the necessary claim limitations disclosed by Villanueva et al., Mooney et al., and Hunt et al. The combination of Kohane et al., Villanueva et al., Mooney et al., and Hunt et al. would allow one to arrive at the present application without employing inventive skill. This combination of the ultrasound-triggered drug delivery system taught by Kohane et al. along with the use of the necessary claim limitations taught by Villanueva et al., Mooney et al., and Hunt et al. would allow a research and development scientist (POSITA) to develop the invention taught in the instant application.
It would have only required routine experimentation to modify the ultrasound-triggered drug delivery system disclosed by Kohane et al. with the use of the necessary claim limitations taught by Villanueva et al., Mooney et al., and Hunt et al. This combined modification would have led to an enhanced ultrasound-triggered drug delivery system that would be beneficial for patients.
In the context of instant method claims 10-14 the desired purpose defines an effect that arises from and is implicit in the method step(s). Thus, where the purpose is limited to stating a technical effect that inevitably occurs during the performance of the claimed method step(s), and is therefore inherent in that/those step(s), that technical effect is not limiting to the subject-matter of the claim. Thus, the present method claim, defining the application/use of the composition according to the prior art, and defining its purpose as "use", is anticipated by any document of the state of the art describing a method of application/use although not mentioning this specific use.
Conclusion
No claims are allowed.
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/JOHN W LIPPERT III/Examiner, Art Unit 1615 /Robert A Wax/Supervisory Patent Examiner, Art Unit 1615