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 .
Election/Restrictions
To summarize the current election, the applicant elected Group I.
The restriction is made FINAL.
Claims 25-26, 28-35, 37-39 and 41-42 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. The applicant is reminded to update their claim status identifiers in each reply containing claims.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 43-44 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are drawn to a microparticle cavitation nucleus capable of undergoing stable and/or inertial cavitation when exposed to ultrasound frequency of 0.1 to 30 MHz and having a cavitation threshold with the range of 0.1 MPa to 10 MPa with this frequency. The microparticle is structurally recited as a core-shell microparticle comprising a degradable polymer at least two surface cavities and one or more drugs. The drugs are selected from a particular listing of categories and both the microparticle and cavities have a recited average diameter. The instant disclosure provides examples of a microparticle that meet the structural recitation for size and surface cavities that are composed of poly(lactide-co-glycolide) (PLGA). The cavities are shown as indentations on the surface on the microparticles that have a blind end or an open end due to intersecting with a more interior cavity (see figure 1 and figure 2c and 2d). The specification details testing the microparticles made by employing phosphate buffered saline in a double emulsion process (see figure 5). All of the microparticles show a cavitation intensity when exposed to 1.1 MHz ultrasound (see page 24 lines 1-11). There is no discussion of the necessary structure amongst the possible configurations of core-shell microparticles having two or more surface cavities that yields the cavitation ability or how the structure is configured such that the cavitation occurs across the range of applied frequencies and in the claimed range of pressures. No other biodegradable polymers are made into microparticles that have the claimed cavitation functionality. In addition, no particular surface architecture is connected to the claimed cavitation such that the necessary modifications required to yield a desired inertial or stable cavitation are clear. Thus the disclosure does not provide a sufficient structure-function correlation for the claims. As a result, the artisan or ordinary skill would not have deemed the applicant to be in possession of the scope of invention as currently claimed.
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 43-45 is 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.
Due to the lack of adequate description of the structure necessary to yield the functional limitation of claims 42-44, the scope of microparticles that meet the claim limitations is unclear.
For the sake of compact prosecution and the application of prior art, a microparticle of instant claim 19 will be deemed sufficient to meet the instant functional limitations. Clarification is still required.
The structure of the claimed microparticles of claim 45 is unclear. As recited, the microparticle has surface cavities. They are shown as indentions in the surface of the microparticles that have a blind end or an open end due to an intersection with a pore(s) below the surface (see instant figures 1 and 2). It is not clear how a gas bubble is held/retained in an indention on the surface of a microparticle. The specification details that gas bubbles form when dried or lyophilized microparticles are suspended in a liquid (see page 12 lines 13-14). It is unclear which variables determine where on a microparticle surface bubbles form and the duration of time that they exist. Since no gas interface stabilizing component is required in the pharmaceutically acceptable carrier, water, or aqueous solution that is present in the claimed composition, the presence of the gas bubble would be transient. Thus it is unclear the circumstances and structural requirements of the composition under which a gas bubble would form in at least one of the two or more surface cavities. As a result the metes and bounds of the claim are unclear.
For the sake of compact prosecution and the application of prior art, a microparticle of instant claim 19 that has been lyophilized and suspended in an aqueous medium will be deemed sufficient to meet the instant claim limitations. Clarification is still required.
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.
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 19-24 and 42-45 are rejected under 35 U.S.C. 103 as being unpatentable over Seekell et al. (Proceedings of the National Academy of Sciences 2016 113(44):12380-12385 + Supplemental Information) in view of Polizzotti et al. (US PGPub No. 2016/0067276) and Bartels (US PGPub No. 2011/0189307) as evidenced by Guimberteau et al. (US PGPub No. 2007/0264346).
Seekell et al teach core-shell PLGA microparticles that have a porous shell and encapsulate oxygen (see abstract; instant claims 19 and 22). They provide microparticles with an average size less than 10 mm and pores that occur at the surface of the shell (cavities) (see page 12381 second column last partial paragraph and figure 2 A, C, I, and K; instant claim 19). The average pore diameter of their formulation 4 was between 0.1 and 0.3 mm (see figure 2 K, L, M, and O; instant claim 19). Seekell et al. provide the microparticles as lyophilized (freeze dried) particles and dispersed in ultra-pure water (see page 12384 second column fourth full paragraph-last partial paragraph; instant claim 23-24 and 45). They also detail their oxygen containing microparticles for oxygen delivery therapeutic applications (see page 12384 second column second full paragraph). The presence of a drug in the microparticle as instantly claimed is not detailed.
Polizzotti et al. also teach core-shell PLGA microparticles that encapsulate oxygen similar to those of Seekell et al. (see paragraphs 344-348). They further detail including a drug in the polymer shell of such microparticles (see paragraph 19). Polizzotti et al. additionally each application of the oxygen releasing microparticles via topical wound healing compositions for burns and other skin wounds (see paragraphs 225 and 258). They further teach providing the microparticles in an aqueous suspension (see paragraph 28-29; instant claims 23-24).
Bartels teaches the delivery of oxygen in combination with various drugs from a topical composition to wounds, ulcers and burns (see abstract and paragraphs 21 and 67). The drugs include anti-inflammatory agents such as dexamethasone as well as immunomodulators such as cyclosporin and tacrolimus (see paragraph 67 and 71-72). Both cyclosporin and tacrolimus are immunosuppressants (see Guimberteau et al. paragraph 259).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include dexamethasone, tacrolimus or cyclosporin in the shell of the PLGA microparticles of Seekell et al. in light of Polizzotti et al. and Bartels. This modification would have been obvious so as to direct the composition toward utility for wound healing as Polizzotti et al. suggest from similar oxygen delivering microparticles. The modifications are also obvious to provide additional drugs as suggested by Polizzotti et al. that were known for combination with delivered oxygen to address would healing in light of Bartels as the application of the same technique to a similar product in order to yield the same improvement. Inclusion in an aqueous suspension as detailed by Seekell et al. and Polizzotti et al. would follow. According to MPEP 2145II, mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention In re Wiseman, 596 F.2d 1019, 201 USPQ 658 (CCPA 1979). In addition, the fact that an inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). The microparticles and their aqueous suspension provide the claimed structural limitations. Absent evidence to the contrary, they also would provide the recited functions (see instant claims 43-45). Therefore claims 19-24 and 42-45 are obvious over Seekell et al. in view of Polizzotti et al. and Bartels as evidenced by Guimberteau et al.
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 19-24 and 42-45 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of copending Application No. 18/010216 (reference application) in view of Reb (previously cited).
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims recite core-shell particles comprising a biodegradable polymer with at least two surface cavities. The polymers include aliphatic polyester and the shell contains drug. The size of the microparticles meet the instant limitations. The copending claims also recite the presence of a contrast agent in the particles. Particular drugs are not recited by the copending claims.
Reb teaches a variety of drugs to include in a polymeric microparticle that also contains a contrast agent (see abstract and claims 1 and 9). These drugs include the immunosuppressant cyclosporine as well as dexamethasone (see paragraphs 150 and 161). They additionally teach dispersion of the particles in a pharmaceutically acceptable solution, that may be aqueous, for administration (see paragraphs 129-130 and 224).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select dexamethasone or cyclosporine as the drugs in the particles of the copending claims because they were known to be included along with contrast agent in microparticles, in light of Reb. This modification is obvious as the simple substitution of one known element for another in order to yield a predictable outcome. Inclusion of the particles in an aqueous liquid prior to administration would follow. Routine work and the sizes permissible in the range of possible shell thickness yield a range of possible cavity diameters that overlap with or embrace the instant range and render them obvious. “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); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed.Cir. 1990)” (see MPEP 2144.05). According to MPEP 2145II, mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention In re Wiseman, 596 F.2d 1019, 201 USPQ 658 (CCPA 1979). In addition, the fact that an inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). The microparticles and their aqueous suspension provide the claimed structural limitations. Absent evidence to the contrary, they also would provide the recited functions (see instant claims 43-45). Therefore claims 19-24 and 43-45 are obvious over claims 1-21 of copending Application No. 18/010216 (reference application) in view of Reb
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant's arguments filed October 1, 2025 have been fully considered. In light of the amendment to the claim, the previous ground of rejection under 35 USC 102 and 35 USC 103 are hereby withdrawn. New grounds of rejection are presented in their place to address the new claim limitations.
Conclusion
No claim is allowed.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CARALYNNE E HELM whose telephone number is (571)270-3506. The examiner can normally be reached Mon-Fri 9-5.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert Wax can be reached at (571) 272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CARALYNNE E HELM/ Examiner, Art Unit 1615
/MELISSA S MERCIER/ Primary Examiner, Art Unit 1615