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 Claims
A new claim set was filed on 1/14/26 with the following:
Amended claims
Newly canceled claims
Newly added claims
Previously canceled claims
1-11, 14-16, 18, 21, 28
Previously withdrawn claims
12, 17, 27
Claims under instant examination
13, 19-20, 22-26, 29-34
Maintained 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 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 13, 19-20, 22-26 and 30-34 remain rejected under 35 U.S.C. 103 as being unpatentable over Cai et al. (CN 101716146; published: 6/2/10; in IDS dated 3/19/19), in view of Kondiah et al. (WO 2015/011653; published: 1/29/15; of record) and Satarkar et al. (J Contr Rel, 130, 2008,246-251; of record).
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Cai et al. is directed to vancomycin slow-release microsphere with magnetic field compliance and preparation method thereof (Title). Cai et al. teach crosslinked-chitosan microspheres comprising vancomycin (claimed agent; an anti-bacterial agent; antibody) and nanoscale ferroferric oxide magnetic powder (claimed magnetic nanoparticle) (limitations of instant claims 13, 22-23 and 30-32; Abstract). Cai et al. teach that vancomycin kills bacteria by inhibiting their growth and reproduction (limitation of instant claims 30-33). Cai et al. teach that after being infused to body, the microsphere can gather in local pathologic change part under guidance of outer magnetic field so as to improve local drug concentration and reach the purpose of targeted therapy of drug (limitation of instant claim 13, 22 and 25; Abstract).
Cai et al. teach a method of treating bone infections comprising aggregating the microspheres at the lesion site (i.e., contacting the site of trauma with a chitosan microbead of claim 1) via the guidance of an external magnetic field (limitations of instant claim 13, 22 and 25; see entire reference; e.g., summary of the invention).
With regards to the limitations of instant claim 20, Cai et al. teach the claimed active steps of applying contacting the trauma site with the chitosan microsphere and applying a magnetic field. The MPEP §2111.04 states: “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure….However, the court noted that a "‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’" Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)).” In the instant case, the claim 20 limitation “wherein the method reduces fungi or bacteria present at the site by at least about 20-100% at 72 hours after contact with the chitosan-microbead composition relative to an untreated control site” and claim 22 limitation “wherein agent release is controlled through application of the magnetic stimulus” indicates the intended result of the process step positively recited (“applying a magnetic field to chitosan microspheres disposed within the patient”). That is, since the prior art teaches the same active method steps of the instantly claimed invention, the method taught by Cai et al. must necessarily be capable of producing the same intended use as recited in the instant claims. It is noted that there is no difference between the prior art method steps and the claimed method steps that would result in a different effect.
With regards to the “desired time point” limitation of instant claim 22, one of ordinary skill in the art would understand that in the method of Cai et al., the desired time point to apply the external stimulus is any time after contacting the microspheres to the patient because it is taught that the magnetic field applied keeps the drug-loaded microspheres at the desired location for drug release and minimizes releasing the drug to areas of the body that are not desired.
Ascertainment of the Difference Between the Scope of the Prior Art and Claims
(MPEP §2141.012)
Cai et al. do not teach wherein chitosan is cross-linked specifically with polyethylene dimethylacrylate (PEGDMA), as required by instant claims 13 and 22. However, this deficiency is cured by Kondiah et al.
Kondiah et al. is directed to pH responsive oral polymeric pharmaceutical dosage form (Title). Kondiah et al. teach a dosage form comprising chitosan-poly(ethylene glycol) dimethacrylate-methacrylic acid (CHT-PEGDMA-MAA) copolymer particles, wherein CHT-PEGDMA-MAA demonstrate highly efficient systems in encapsulating a protein and/or peptide (conclusions).
With regards to the drug release limitations of instant claim 19, Cai et al. teach the following drug release from the microspheres: 89.5% in 24 hours, 84.6% in 16 hours, 77.5% in 4 hours, 72.7% in 2 hours, and 56.6% in 1 hour (see detailed description section). Cai et al. do not specifically teach wherein the composition releases at least about 0.2-50 µg of an antimicrobial agent per hour or wherein the microbead releases about 2 µg-1000 mg of the agent in 1-72 hours, as required by instant claims 19 and 24, respectively.
Although Cai et al. teach the application of a magnetic field, they do not specifically teach wherein the stimulus is applied for 30 minutes, as required by instant claim 26.
Cai et al. and Kondiah et al. do not teach wherein the method comprises applying high frequency alternating magnetic field to the site, as required by instant claims 13, 22, 25 and 34. However, this deficiency is cured by Satarkar et al.
Satarkar et al. is directed to magnetic hydrogel nanocomposites for remote controlled pulsatile drug release. Satarkar et al. teach that a high frequency alternating magnetic field (AMF) was used to trigger the on-demand pulsatile drug release from the nanocomposites (Abstract). Application of AMF resulted in uniform heating with the nanocomposites leading to accelerated collapse and squeezing out large amounts of imbibed drug (release at a faster rate) (Abstract).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, at the time the invention was made, to substitute equivalents, each of which is taught by the prior art to be useful for the same purpose (cross-linked- chitosan particles loaded with peptide drug of Cai et al. with that of Kondiah et al. for the purpose of delivering drugs) (See MPEP 2144.06-II).
The drug release amount and amount of time the stimulus is applied 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 would reasonably expect success. It would have been customary for an artisan of ordinary skill to determine the optimal amount of drug to incorporate in the microspheres in order to best achieve the desired results as such would provide advantageous for delivering an efficacious amount of active agent (e.g., vancomycin) in order to treat the bone infection in the patient. Furthermore, based on the drug release profile, one of ordinary skill in the art would understand that the amount of time the magnetic field was applied would affect how long the drug-loaded microspheres stayed at the desired site in the body for its drug release. It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to engage in routine experimentation to determine optimal or workable ranges that produce expected results. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. In re Aller, 220 F. 2d 454, 105 USPQ 233 (CCPA 1955).
Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art to apply the high frequency alternating magnetic field taught by Satarkar et al. to any known magnetic drug delivery product such as those taught by Cai et al. and the results would have been predictable to one of ordinary skill in the art. That is, using the known technique of applying a high frequency alternating magnetic field in order to enhance the release rate of the encapsulated drug would have been prima facie obvious to one of ordinary skill (See MPEP 2143C: Use of known technique to improve similar devices (methods, or products) in the same way).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Thus, the claimed invention was prima facie obvious before the effective filing date of the claimed invention.
Claim 29 remains rejected under 35 U.S.C. 103 as being unpatentable over Cai et al. (CN 101716146; published: 6/2/10; in IDS dated 3/19/19), in view of Kondiah et al. (WO 2015/011653; published: 1/29/15; of record) and Satarkar et al. (J Contr Rel, 130, 2008,246-251; of record) as applied to claims 13, 19-20, 22-26 and 30-34 above, and further in view of Alcala-Cerra et al. (Rev Esp Cir Ortop Traumatol. 2014, 58(3), 182-191; of record).
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Cai et al., Kondiah et al. and Satarkar et al. teach the limitations of instant claims 13, 19-20, 22-26 and 30-34 (see details in above rejection).
Ascertainment of the Difference Between the Scope of the Prior Art and Claims
(MPEP §2141.012)
Cai et al., Kondiah et al. and Satarkar et al. do not teach wherein the trauma is selected from the group consisting of a fracture, open fracture, wound, complex wound and surgical site, as required by instant claim 29. However, this deficiency is cured by Alcala-Cerra et al.
Alcala-Cerra et al. is directed to application of vancomycin powder into the wound during spine surgery (Title). Alcala-Cerra et al. teach that application of vancomycin powder into the wound was associated with a significantly reduced risk of surgical site infections, without increasing pseudo-arthrosis or adverse events (Abstract).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
The disclosures of Cai et al. and Alcala-Cerra et al. are each directed to the use of vancomycin. Therefore, it would have been prima facie obvious for a person of ordinary skill in the art to combine their respective teachings and to use the vancomycin-containing composition of Cai et al. to reduce the risk of surgical site infections, as instantly claimed, with a reasonable expectation of success, at the time of the instant application. A person of ordinary skill would have been motivated to do so because Alcala-Cerra et al. teach that vancomycin can significantly reduce the risk of surgical site infections, without increasing pseudo-arthrosis or adverse events (Abstract).
Thus, the claimed invention was prima facie obvious before the effective filing date of the claimed invention.
Response to Arguments
Applicants’ arguments have been fully considered, but are not found persuasive.
Applicants argue that there is no basis – mechanistic, scientific, or otherwise – to contend that Cai teaches or suggests any magnetic stimulus, let alone the claimed alternating magnetic stimulus, can be used to induce drug release (Remarks: p. 6, 1st full ¶).
This is not found persuasive. It is first noted, that the 103 rejection relies upon the teachings of Cai, Kondiah and Satarkar, not just Cai. 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). Since the instant rejection is an obviousness-type rejection, none of the references (i.e., Cai, Kondiah and Satarkar) has to teach each and every claim limitation. It is the combination of the prior art references that renders the instant claims prima facie obvious and applicants did not provide any evidence that one of skill in the art would not have been motivated or would not have reasonably expected to be successful in arriving at the claimed invention as set forth in the rejection above. Secondly, the Examiner does not indicate that Cai teaches that its application of magnetic field is directly responsible for drug release. The Examiner states there is an indirect relationship. Cai teaches the applied magnetic field produces site-specific targeting and because the microspheres of Cai are characterized by slow-release, the release of drug occurs after the microspheres are infused to body and after the application of magnetic field (i.e., indirectly releases drug). Furthermore, as indicated in the instant rejection, Satarkar is relied upon, not Cai, for such claimed limitation that Applicants argue above. Satarkar teaches the method of applying a magnetic field, specifically an alternating magnetic stimulus, to a drug delivery system in order increase the release of the drug via magnetic-induced heating. That is, Satarkar provides a teaching, suggestion and motivation as to why one of ordinary skill in the art would apply an alternating magnetic stimulus to the magnetic nanoparticle-containing drug delivery system.
Applicants argue that the application of an alternating magnetic field to Cai’s particles would destroy the entire principle of operation of Cai’s particles (Remarks: p. 6, last ¶ to p. 7, first full ¶).
This is not found persuasive. In response, Cai teaches using a magnetic field to bring the drug delivery system (i.e., cross-linked chitosan microspheres comprising a magnetic nanoparticle and agent) to the target site and Satarkar teaches using a different type of magnetic field (i.e., alternating magnetic field) for a different purpose (i.e., to increase release of the drug). Using a magnetic field for targeted therapy and using an alternating magnetic field for the purpose of increasing drug release can be used together and there is no evidence that one does not destroy the purpose of the other. It is noted that the rejection does not substitute one magnetic stimulus with another as suggested by the Applicants on p. 6, last ¶ (“replacing Cai’s static field with an alternating one therefore destroys the very behavior Cai depends on”).
Conclusion
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 GENEVIEVE S ALLEY whose telephone number is (571)270-1111. The examiner can normally be reached Monday-Friday 8:00-5:00.
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/GENEVIEVE S ALLEY/ Primary Examiner, Art Unit 1617