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 .
Status of the Claims
Claims 1, 2, 5, 8, 10, 11, 13-15, 17, 23-25, 29, 32, 37, 39, 49, and 55 are pending.
Claims 8, 10, 11, 13-15, 17, 23-25, 29, 32, 49, and 55 are withdrawn from consideration as directed to non-elected inventions.
Claims 1, 2, 5, 37, and 39 are presented for examination and rejected as set forth in greater detail below.
Claim Interpretation
Applicants Claims are directed to nanoparticle compositions comprising the elected copolymer (shown above) encapsulating perfluorocarbons which must include perfluorooctyl bromide (perflubron). Claim 2 limits the size of each of the polyoxyethylene and polycaprolactone blocks of the copolymer, with Claim 5 specifying the polydispersity index of the particles. Claim 37 specifies that the perfluorocarbon is to be perfluorooctyl bromide. Claim 39 specifies the nanoparticle is to contain at least one additional therapeutic or diagnostic agent, have a particular diameter, and again a particular polydispersity index. The examiner notes that polydispersity indices are used to assess the size distribution of particles about a given value. The Examiner will consider art describing or advocating providing particles of uniform size sufficient to address the polydispersity indices recited by the claims.
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 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 1, 2, 5, 37, and 39 are rejected under 35 U.S.C. 103 as being unpatentable over Lavasanifar (U.S. PGPub. 2010/0137206), in view of Walovitch (WO2005/120587), and Hecht (WO2011/019419).
Lavasanifar describes micelle forming polyoxyethylene polyester block copolymers compatible with a wide variety of bioactive agents, which serve as suitable carriers for those compounds, or may have them, or targeting moieties, bound thereto. (Abs.); [0003]. In general, Lavasanifar teaches the generic compound of formula I (below) as the particular polymer of the invention. [0011-13].
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The Examiner notes that Lavasanifar defines x as an integer of between 10-300, an integer between 5 and 100, L1 a carbonyl containing linker, and R1 an active agent. Id. Lavasanifar indicates these compounds of formula I form a micelle around a bioactive agent contained within the polymer shell. [0021]. Lavasanifar indicates bioactive agents are to be construed broadly as including any substance intended for diagnosis, treatment, or prevention of disease. [0092]. Of particular interest to the instant claims is the disclosure in Lavasanifar of the compound referred to as “PEO-b-PChCl,” a copolymer of polyethylene oxide and polycaprolactone modified to contain a cholesteryl pendant group. Pg.13, “Example 6.” (the examiner notes that while the structure provided in the PGPub reflects a butyl, rather than the claimed pentyl, chain, by the disclosure’s reference to polymerization via ring-opening of a caprolactone monomer, the Examiner considers the omission of two methylene groups in the image below to represent a typographic error).
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The m and n variables of the POE-b-PChCl of Lavasanifar correspond to the x and y variables of the generic formula I provided, meaning that the POE and polycaprolactone blocks of the Lavasanifar compound overlap in size with the POE and polycaprolactone blocks of the claimed polymer, rendering them obvious thereby. See In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003) (“A prima facie case of obviousness typically exists when the ranges of a claimed composition overlap the ranges disclosed in the prior art.”). While no particular particle size of these block copolymers are described, Lavasanifar indicates that a variety of empty micelles of representative examples of the compound of formula I possess diameters of between 48-99 nm and polydispersities of less than 0.3, and drug loaded micelles of average diameter between 68-600nm an polydispersities of between 0.15-0.72, ranges overlapping and therefore rendering obvious those limitations of Claims 1 and 39. Pg.19, “Table 2”; see Peterson, supra.
Despite teaching bioactive agent encapsulating micelles of the presently claimed POE-b-PChCl possessing block sizes, micelle sizes, and polydispersities overlapping those of the present claims, Lavasanifar does not particularly describe the inclusion of a perfluorocarbon, either alone or in combination with an additional active agent as required by Claims 1 and 39.
Walovitch describes polymeric particles which are used to encapsulate perfluorocarbons to provide contrast agents with significantly enhanced images. (Abs.). Walovitch indicates that in preferred embodiments the microparticles contain a polymer, lipid, and perfluorocarbon gas. (Pg.10). PEG copolymers are identified as suitable for use in the formation of such particles, and Cholesterol is identified as a particular lipid useful in the stabilization of the perfluorocarbons contained within the polymeric particles. (Pg.10-12).
Hecht indicates that tumors can be selectively targeted by compositions which combine microbubbles encompassing a perfluorocarbon gas core with additional active and chemotherapeutic agents for use in imaging. (Abs.); [0006]. While listed as a “chemotherapeutic agent,” Hecht enumerates the presently claimed perflubron as suitable for use with the microbubble compositions. (Pg. 19). Hecht indicates that PEG-PCL copolymers are particularly useful for encapsulating the fluorocarbon gasses as well as additional chemotherapeutic agents. [0087-88].
The art available to the skilled artisan at the time the instant application was filed therefore teaches the use of the presently claimed POE-b-PChCl possessing block sizes, micelle sizes, and polydispersities overlapping those of the present claims as useful for encapsulating a wide variety of active agents, that PEG polymers in combination with lipids such as the cholesterol of the present claims and the Lavasanifar copolymers serve to improve the solubilization of perfluorocarbons in polymeric particles, and that the instantly claimed perflubron and additional chemotherapeutic agents were, at the time the instant application was filed, known to be agents usefully incorporated into particles for use as imaging and therapeutic agents.
It must be remembered that “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious.” KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious,” the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR at 1741. The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742.
Consistent with this reasoning, it would have been prima facie obvious to have used POE-b-PChCl possessing block sizes, micelle sizes, and polydispersities overlapping those of the present claims to encapsulate each of perflubron and additional chemotherapeutic agents, to arrive at compositions “yielding no more than one would expect from such an arrangement.”
Response to Arguments
Applicant's arguments filed 24 February 2026 have been fully considered but they are not persuasive.
Applicants argue that Lavasanifar and Walovitch fail to teach the encapsulation of perflubron by asserting that Walovitch teaches the formation of microparticles rather than nanoparticles of the claims and of Lavasanifar. This argument misapprehends the Examiner’s stated rationale for relying on the combined teachings of each of Lavasanifar and Walovitch. As set forth previously and again above, Lavasanifar establishes that the PEG/PCL polymer with a cholesterol moiety grafted to the polycaprolactone (hereafter “the copolymer”) was, at the time the instant application was filed, known in the art as useful for the encapsulation of a wide variety of pharmaceutical agents. This was, and remains, combined with the teachings of Walovitch which establishes that PEG copolymers were, at the time the instant application was filed, known to encapsulate perfluorocarbons for pharmaceutical use, and that the use of cholesterol in such compositions serves to stabilize those encapsulates.
Applicants are reminded that the rejections of record are not based on the combination of the teachings of Lavasanifar and Walovitch, but rather on what Lavasanifar and Walovitch combined with the teachings of Hecht convey to the skilled artisan. Applicants are reminded that it is not possible to establish the non-obviousness of an invention rendered obvious by the combined teachings of multiple prior art references by arguing that each of the references relied upon fails to teach the entirety of the invention which has been claimed; the absence of a single anticipatory reference is implied by both the reliance on the combined teachings of multiple references as well as the fact that the rejection being made is one of obviousness under 35 U.S.C. 103 rather than any of the subsections of 35 U.S.C. 102. MPEP § 2145(IV), see In re Keller, 642 F.2d 413, 426 (C.C.P.A. 1981) (citing Application of Young, 403 F.2d 754, 757 (C.C.P.A. 1968) (indicating that "[O]ne cannot show non-obviousness by attacking references individually where ... the rejections are based on combinations of references"). Here, Lavasanifar establishes that the copolymer was known to be useful for the encapsulation of a wide variety of pharmaceutical agents, and Walovitch establishes that combinations of PEG copolymers and cholesterol were known to encapsulate perfluorocarbons for pharmaceutical use. This understanding was, and is, combined with the teachings of Hecht to establish that PEG-PCL copolymers, such as the copolymer of the claims, were known to encapsulate perfluorocarbons including the perflubron of the instant claims.
The art establishes that PEG copolymers and cholesterol advantageously stabilize encapsulated perfluorocarbons, and that PEG-PCL copolymers were known to be effective in encapsulating perfluorocarbons including the instantly claimed perflubron. On this basis, the Examiner concluded that it would have been prima facie obvious to have utilized the PEG/PCL/cholesterol copolymer of the claims and the Lavasanifar reference as a PEG/PCL copolymer to encapsulate as an active agent the perflubron of the claims. This is because the PEG/PCL/cholesterol copolymer of Lavasanifar and the claims combines both the PEG/PCL copolymer the art establishes is effective in encapsulating perflubron with the cholesterol that Walovitch establishes helps stabilize encapsulated perfluorocarbons.
Applicants assertion that Hecht teaches perflubron as among a variety of alternative active agent which can be encapsulated by PEG/PCL copolymers does nothing to detract from the fact that Hecht enumerates perflubron as one of the pharmaceutical agents suitable for encapsulation within PEG/PCL copolymers. Applicants are reminded that it is well settled that it is a matter of obviousness for one of ordinary skill in the art to select a particular component from among many disclosed by the prior art as long as it is taught that the selection will result in the disclosed effect, even when the possible selections number 1200 or in the thousands. Merck & Co., Inc. v. Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed. Cir. 1989); In re Corkill, 771 F.2d 1496, 1500 (Fed. Cir. 1985).
Applicants assertion that perflubron loaded nanoparticles “can be difficult to form” presents no evidence, let alone sufficient evidence, to overcome the prior art’s presumption of enablement and operability and are unpersuasive as a result. See In re Antor Media Corp., 689 F.3d 1282, 1288 (Fed. Cir. 2012)(indicating that "a prior art publication cited by an Examiner is presumptively enabling barring any showing to the contrary by a patent applicant”).
Applicants arguments concerning the utility of the Lavasanifar copolymers and the Walovitch compositions, as well as the applicants findings that the copolymer can be used to encapsulate perflubron are unpersuasive. Applicants are reminded that the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981), In re Kotzab, 217 F.3d 1365, 1370 (Fed. Cir. 2000). Here, the art of record establishes that PEG copolymers and cholesterol advantageously stabilize encapsulated perfluorocarbons, and that PEG-PCL copolymers were known to be effective in encapsulating perfluorocarbons including the instantly claimed perflubron. On this basis, the Examiner concluded that it would have been prima facie obvious to have utilized the PEG/PCL/cholesterol copolymer of the claims and the Lavasanifar reference as a PEG/PCL copolymer to encapsulate as an active agent the perflubron of the claims. As a result, the Examiner has concluded that the claims, and results applicants observe, are precisely what a skilled artisan would expect from modifying the art identified by the Examiner in the manner set forth previously and again above. This is because if an applicant merely submits evidence to establish the obtention of a result which would have been expected based upon the knowledge of the worker in the art, the evidence merely buttresses the Examiner’s case for obviousness. In re Skoll, 523 F.2d 1392, 187 USPQ 481, 484 (CCPA 1975), In re Gershon, 372 F.2d 535, 538, 152 USPQ 602, 604 (CCPA 1967), In re Skoner, 517 F.2d 947, 950 (CCPA 1975). In addition, the advantage relied upon must be a significant advantage. See In re Nolan, 553 F.2d 1261, 193 USPQ 641 (CCPA 1977).
For at least these reasons, applicants arguments are unpersuasive.
Conclusion
No Claims are allowable.
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 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 SEAN M BASQUILL whose telephone number is (571)270-5862. The examiner can normally be reached Monday through Thursday, 5:30 AM to 4 PM.
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, Ali Soroush can be reached at (571) 272-9925. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SEAN M BASQUILL/Primary Examiner, Art Unit 1614
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