DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . 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.
Status of the Claims
The response and amendment filed 04/17/2026 is acknowledged.
Claims 29-31, 33, 42-46, 55-61, and 63-65 are pending.
Claims 63-65 are new and have been rejected.
Claim 33 is objected to.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. Rejections not reiterated herein have been withdrawn. Rejections of canceled claims have been withdrawn.
Withdrawn
The rejection of claim 32 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends has been withdrawn because of Applicant’s amendment.
The rejection of claims 29 and 52 under 35 U.S.C. 103 as being unpatentable over Labib, US 20110300202 in view of Buevich, US 20140046350 as applied to claims 29, 30-32, 42-46, 54-57, and 60-61 above, and further in view of Melo, Materials Science and Engineering C, 112, 2020 and Shoichet, US 9205047 has been withdrawn because of Applicant’s amendment.
Response to Argument
Applicant's arguments filed 04/17/2026 have been fully considered but they are not persuasive.
Applicant has argued that as described in the published application at paragraph [0090], minocycline has a high water- solubility, and rifampin has a low water-solubility. Applicant argues the discovery that both minocycline and rifampin, which have significantly different solubility in water, when present in the presently claimed composition provide enhanced the release of the other, is unexpected. Applicant argues that by combining rifampin and minocycline, "wherein at least some of said rifampin is present in the form of discrete first particles within said composition formed by melt processing, and at least some of said minocycline is present in the form of discrete second particles within said composition formed by melt processing" and "wherein said rifampin has a respective cumulative release of said rifampin from said composition formed by melt processing to an aqueous environment that is greater than would occur with an identical composition absent said minocycline, and wherein said minocycline has a respective cumulative release of said minocycline from said composition formed by melt processing to an aqueous environment that is greater than would occur with an identical composition absent said rifampin, and wherein said composition is capable of providing drug release to said aqueous environment at a clinically effective concentration for a time duration of at least 40 days" in a composition as claimed, it is possible to take advantage of the significant difference in water solubility of the two drugs so that the cumulative release of the two drugs is increased beyond what would be expected by each drug individually.
This argument is unpersuasive. The prior art of record, i.e., Buevich, exemplifies the combination of rifampin and minocycline wherein each antibiotic is present in an amount within the claimed range, e.g., 10wt% minocycline and 10wt% rifampin (Buevich, e.g., Examples, e.g., 0080-0085). Buevich teaches implantable devices improved by the antibiotic combination of minocycline and rifampin (Buevich, e.g., 0084, catheter and claims 46-47). The combination of minocycline and rifampin was a known antibiotic alternative for ciprofloxacin (Buevich, e.g., 0069-0070). The combination of minocycline and rifampin is shown to be effective to inhibit S. epidermidis and S. aureus (Buevich, e.g., 0084, Tables 2-3).
To the extent that Applicant is relying on the combination of rifampin and minocycline for synergistic effects, it is noted that the degree to which the combination of rifampin and minocycline contributes to increased release of each drug compared to the respective release when formulated separately, is also present in the prior art of record. That is, the prior art teaches the same combination and therefore the synergistic effects (release properties) are inherent to the prior art combination of expressly taught by Buevich. Since the rifampin/minocycline combination was known and used by the prior art, advantages which stem solely from this combination, e.g., increase of both the minocycline and rifampin compared to either drug alone was a latent property of the prior art combination absent evidence to the contrary.
Applicant has argued Blend 11 in table 1 shows a composition without polycaprolactone. Applicant has also pointed to table 8 and ¶ 0170 as showing unexpected release from minocycline and rifampin.
This is unpersuasive. It is acknowledged that the specification exemplifies compositions without caprolactone. However, Applicant has not clearly explained how the data in table 8 provides evidence that the subject matter of claim 29 is commensurate in scope with unexpected results. Applicant does not explain, e.g., which of the blends show unexpected results.
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As seen in Table 8, blends 6 and 7 lack either minocycline or rifampin. Blends 11, 12, and 13 lack either PEG or PCL or both. Comparing blends 6 and 7 with blends 11, 12, and 13 is of little probative value since the blends differ by more than one variable. From the data in Table 8, it is manifestly clear that the combination of EVA, PEG, PCL, Rif and Mino provides an order of magnitude difference in the release rate of both Rif and Mino at day 30. Thus, to the extent the best results in table 8 (Blends 9, 10, and 14) are the unexpected results proffered by Applicant, these results have only been shown for a host polymer containing two specific release modifying materials, i.e., PEG and PCL, and two specific antibiotics, i.e., Rif and Mino. Thus, claim 33 was indicated as allowable in the previous office action.
As previously explained: The current specification, e.g., Table 8, blend 8 compared with blend 11 show results both with PCL (blend 8) and without PCL (blend 11). According to table 8, the blend with PCL releases more minocycline and rifampin than the blend without PCL. The skilled artisan could not have predicted that the inclusion of PCL would result in increased release of minocycline and rifampin as shown even if contemplating the modification of compositions suggested by Labib. Polycaprolactone is relatively hydrophobic compared to polyethylene glycol. While Buevich teaches polymer composition may be used to alter release rate of drug from the composition, the skilled artisan would have likely predicted that the addition of caprolactone would result in decreased release of minocycline and/or rifampin since Buevich suggests polymers with limited water uptake, i.e., more hydrophobic, will retard release of agents (Buevich, e.g., 0049). Thus, the subject matter of claim 33 is commensurate in scope with materials having properties which could not have been predicted by the skilled artisan before the effective filing date of the presently claimed invention and this evidence outweighs the evidence of obviousness for the subject matter of claim 33.
Applicant has argued the outstanding Office Action relies upon Buevich et al. for the disclosure of "articles comprising a polymer matrix containing antimicrobial agents...which articles contain antimicrobial agent in amounts effective to reduce post-surgical implant infection..." (Office Action at page 12). Applicant argues that Buevich et al. describe a surgical mesh having a biodegradable coating where a biodegradable polymer, which may contain a drug, is applied by spray or dip coating. See Buevich et al. at paragraphs [0038]-[0039]. Applicant argues this is not a suggestion to provide a composition as claimed "wherein said rifampin has a respective cumulative release of said rifampin from said composition formed by melt processing to an aqueous environment that is greater than would occur with an identical composition absent said minocycline, and wherein said minocycline has a respective cumulative release of said minocycline from said composition formed by melt processing to an aqueous environment that is greater than would occur with an identical composition absent said rifampin, and wherein said composition is capable of providing drug release to said aqueous environment at a clinically effective concentration for a time duration of at least 40 days."
This argument is unpersuasive. To the extent that the claimed invention requires melt processing, it is noted that product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps. See MPEP 2113. Additionally, Labib teaches articles comprising composite prepared by uniformly dispersing bioactive agent in a polymer melt (Labib, e.g., 0022). Labib teaches one or more melt processable polymeric materials which polymer materials are suitable for implantation in a living mammal (Labib, e.g., 0111-0117). Melt processing of polymer melt material and bioactive agent is exemplified in Labib, e.g., example 1, 0122-0129 and examples 2-5. This includes melt processing host polymer EVA with at least one release modifying material (PEG) and bioactive agent to form a bioactive agent polymer dispersion (Labib, e.g., 0134-0136). Labib teaches the melt processing method including at least one bioactive agent in the melt processing step with melt processable polymer materials enables the formation of two solid solution phases in the formed polymer matrix (Labib, e.g., 0119 and 0129). The technique of melt processing enables production with lower cost and ease of fabrication combined with extended drug release and essentially constant drug release after an initial induction period, which allows long term antimicrobial effect thereby satisfying needs in the art (Labib, e.g., 0022). Labib attributes the observed extended, essentially constant, drug release profile to the bioactive agent being in the form of particles and the unique phase structure of the composite enabled by melt processing (Labib, e.g., 0154).
Applicant argues Buevich et al. teach that the coated mesh only elutes drug for between 1 to 10 days. See Buevich et al. at paragraph [0041]. Applicant argues Buevich et al. teach away from the presently claimed invention.
This is unpersuasive. Buevich, e.g., 0041 teaches delivery of antimicrobial drugs, e.g., combinations of rifampin and minocycline, can create an inhibition zone against bacterial growth and colonization surrounding the implant, and that the time may be modified, e.g., as desired, e.g., usually about 30 days or less. Beuvich exemplifies release of rifampin and minocycline specifically over 32 days (Beuvich, e.g., Table 4, 0085). There is significant overlap with the claimed range and the range suggested by Beuvich. Further, there is nothing in Beuvich which would have led the skilled artisan to conclude that antimicrobial release should not extend into the presently claimed range. To the contrary, Beuvich suggests the release time frame could be optimized depending on the expected need for antimicrobial activity to create a zone of inhibition against bacterial growth and colonization surrounding the medical device. Additionally, Labib teaches wherein antibiotic release is effective to reduce biofilm reduction for at least 30 days (Labib, e.g., claims 27-28). Thus, there was a teaching in the cited prior art which recognized a need to optimize antibiotic release which includes periods of time greater than 30 days.
Applicant argues Darouiche does not teach a powder, and the skilled artisan, reading Darouiche would understand that Darouiche teaches dissolving minocycline and rifampin in a solvent.
This argument is unpersuasive. The claimed invention is directed to a product rather than a method of producing a composition. While the claimed invention includes the product by process limitation wherein said composition is formed by melt processing said host polymeric material, said at least one release-modifying material, said first drug, and said second drug, this limitation is suggested by Labib as set forth in the modified rejection below. Similarly, while the claimed invention includes the limitation of wherein at least some of said first drug is present in the form of discrete first particles within said composition formed by melt processing, and at least some of said second drug is present in the form of discrete second particles within said composition formed by melt processing, this limitation is suggested by Labib as set forth in the rejection.
Applicant argues Labib 185 does not cure the deficiencies in the combined teachings of Labib and Beuvich argued above with respect to claim 29.
This is unpersuasive. Applicant’s arguments regarding the combined teachings of Labib and Beuvich are unpersuasive as enumerated above. Labib 185 was cited for teaching polymer compositions like those of Labib and Beuvich which have been processed into the form of a sleeve. Thus, Labib 185 cures any deficiency in the combined teachings of Labib and Beuvich with respect to the subject matter of claims 56-59.
Modified Rejections Necessitated by Applicant’s Amendment
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 of this title, 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.
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 29, 30-31, 42-46, 55-57, 60-61, and 63 are rejected under 35 U.S.C. 103 as being unpatentable over Labib, US 20110300202 in view of Buevich, US 20140046350.
Labib teaches a composition comprising a thermoplastic polymeric composite matrix (Labib, e.g., 0022). The matrix comprises a host polymer, e g., polyurethane, polysilicone, polyethylene glycol, ethylene-vinyl acetate copolymers, and blends or mixtures thereof (Labib, e.g., 0085 and claim 11). Labib exemplifies compositions comprising a blend of ethylene vinyl acetate copolymer with polyethylene glycol and at least one active agent (Labib, e.g., example 3, 0134-0143 and example 11, 0165-0168). Active agent includes antibiotic such that the articles have a long-term antibacterial effect (Labib, e.g., claims 6-8, and 22-23, and 0022 and 0109-0110). Bioactive agent may be present in an amount ranging from 2 to about 30 wt% (Labib, e.g., 0090). Labib exemplifies materials comprising a melt blended combination of antimicrobial agent with EVA in a major proportion and polyethylene glycol in a minor proportion (Labib, e.g., examples 3 and 11).
The claimed host polymeric material making up a major portion of said composition reads on ethylene vinyl acetate copolymer which is present as the largest amount of the composition, e.g., Labib, e.g., examples 3 and 11.
The claimed at least one release-modifying material, said at least one release-modifying material being mixed, together with said host polymeric material and making up a minor portion of the composition reads on polyethylene glycol, e.g., Labib, e.g., examples 3 and 11.
Applicable to the limitation wherein said composition is capable of providing drug release to said aqueous environment at a clinically effective concentration for a time duration of at least 40 days: Labib teaches the composition effective for at least 30 days (Labib, e.g., claim 28). Labib, e.g., Figs. 6-8 show release which would extend to at least 40 days. 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). MPEP 2144.05. The skilled artisan would have been motivated to formulate the composition for release of antibiotic, e.g., minocycline and rifampin, over the time frames desired by Labib with a reasonable expectation of success. Buevich teaches drug release may be modified by changing polymer composition, e.g., polymer water affinity (Buevich, e.g., 0049) and amount of drug present in the polymer composition (Buevich, e.g., 0089).
Applicable to claim 29: 1 wt% to 20 wt% of rifampin and 1 wt% to 20 wt% of minocycline Applicable to claim 29: wherein the rifampin and the minocycline do not fully melt during the melt processing:
Labib teaches melt processing to prepare the material so that the bioactive agent, e.g., antimicrobial agent is present in the composition in two phases, e.g., a solid solution phase and discrete particles (Labib, e.g., example 3, 0143: presence of a dispersed phase of un-dissolved ciprofloxacin particles). Further explanation of the melt processing result is found at Labib, e.g., 0034, 0042, 0075, 0083, 0119, 0129, and 0137. The configuration of antimicrobial agent as solid solution and dispersed particles, i.e., so that the drug does not fully melt during the melt processing, provides articles which have a combination of desirable features, e.g., release drug through diffusion, low cost and ease of manufacture combined with extended drug release and essentially constant release rate (Labib, e.g., 0022).
Labib does not expressly teach 1 wt% to 20 wt% of rifampin and 1 wt% to 20 wt% of minocycline.
Buevich teaches articles comprising a polymer matrix containing antimicrobial agents (Buevich, e.g., Abstract, examples, and claims) which articles contain antimicrobial agent in amounts effective to reduce post-surgical implant infection (Buevich, e.g., 0003-0004). Like Labib, Buevich teaches antimicrobial agents incorporated in articles in polymers for controlled release (Beuvich, e.g., 0047-0055). Buevich exemplifies the combination of rifampin and minocycline wherein each antibiotic is present in an amount within the claimed range, e.g., 10wt% minocycline and 10wt% rifampin (Buevich, e.g., Examples, e.g., 0080-0085). Buevich teaches implantable devices improved by the antibiotic combination of minocycline and rifampin (Buevich, e.g., 0084, catheter and claims 46-47). The combination of minocycline and rifampin was a known antibiotic alternative for ciprofloxacin (Buevich, e.g., 0069-0070). The combination of minocycline and rifampin is shown to be effective to inhibit S. epidermidis and S. aureus (Buevich, e.g., 0084, Tables 2-3).
Labib teaches minocycline and/or rifampicin may be used as bioactive agent (Labib, e.g., 0094). Labib does not exemplify an embodiment containing 1 wt% to 20 wt% of rifampin and 1 wt% to 20 wt% of minocycline. However, Buevich teaches minocycline and rifampin used in combination is effective when present in polymer materials in an amount within the claimed range.
Regarding the limitation of wherein at least some of the drug is present in the form of discrete first particles within said composition and at least some of said second drug is present in the form of discrete second particles within said composition formed by melt processing; and
Regarding the limitation of wherein said composition is formed by melt processing said host polymeric material, said at least one release modifying material, said rifampin, and minocycline as found in claim 29:
Labib teaches articles comprising composite prepared by uniformly dispersing bioactive agent in a polymer melt (Labib, e.g., 0022). Labib teaches one or more melt processable polymeric materials which polymer materials are suitable for implantation in a living mammal (Labib, e.g., 0111-0117). Melt processing of polymer melt material and bioactive agent is exemplified in Labib, e.g., example 1, 0122-0129 and examples 2-5. This includes melt processing host polymer EVA with at least one release modifying material (PEG) and bioactive agent to form a bioactive agent polymer dispersion (Labib, e.g., 0134-0136). Labib teaches the melt processing method including at least one bioactive agent in the melt processing step with melt processable polymer materials enables the formation of two solid solution phases in the formed polymer matrix (Labib, e.g., 0119 and 0129). The technique of melt processing enables production with lower cost and ease of fabrication combined with extended drug release and essentially constant drug release after an initial induction period, which allows long term antimicrobial effect thereby satisfying needs in the art (Labib, e.g., 0022). Labib attributes the observed extended, essentially constant, drug release profile to the bioactive agent being in the form of particles and the unique phase structure of the composite enabled by melt processing (Labib, e.g., 0154).
Thus, Labib clearly teaches wherein the composition is formed by melt processing said host polymeric material, the release modifying materials, and the bioactive agents, wherein the bioactive agents are in the form of discrete particles (not fully melted) and solid solution phases of the bioactive agent(s) obtained by melt processing which enables extended, essentially constant, drug release profiles at a low cost with increased ease of fabrication.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the presently claimed invention to modify a polymeric matrix material formed by melt processing a host polymer, at least one release modifying material, and bioactive agents taught by Labib by incorporating a known antimicrobial combination of first and second drug, e.g., minocycline and rifampin, in effective amounts suggested by Buevich to improve the composition in the same way with a reasonable expectation of success. The skilled artisan would have been motivated to select a combination of minocycline and rifampin to inhibit bacteria known to present complications for implantable devices, e.g., S. aureus, thereby reducing colonization of bacteria and reducing infectious complications in the same way reported by Buevich with a reasonable expectation of success. The skilled artisan would have had a reasonable expectation of success because Labib suggests the antimicrobial agent may be selected from minocycline, rifampin and combinations thereof.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the presently claimed invention to incorporate minocycline and rifampin so that they are present in the composition as discrete first and second particles with a reasonable expectation of success. The skilled artisan would have been motivated to incorporate minocycline and rifampin so that they are present in the composition as discrete particles because Labib teaches this technique for formulating antimicrobial agents so that the composition may be formed into useful articles effective to elute drug by diffusion with extended and constant drug release for long term antibacterial effect.
Applicable to claims 30 and 42-43: Labib teaches the composition further comprising plasticizers, colorant, antioxidants, stabilizers, inert fillers, and combinations thereof (Labib, e.g., claim 12 and 0091). Any of these additional materials meet the limitation of a second release-modifying material so long as they are in a minor proportion. Labib teaches the composition containing less than about 25 percent of plasticizers, colorant, antioxidants, stabilizers, inert fillers, and combinations thereof (Labib, e.g., 0091).
Applicable to claim 31: Labib teaches and exemplifies compositions comprising poly ethylene vinyl acetate copolymer as the major component of the thermoplastic matrix material.
Applicable to claim 32: Labib teaches and exemplifies compositions comprising polyethylene glycol in a host polymer matrix as a minor component.
Applicable to claim 44: polyethylene glycol is more hydrophilic than ethylene vinyl acetate copolymer.
Applicable to claim 45: Labib teaches the composition comprising less than about 25 percent of plasticizers, colorant, antioxidants, stabilizers, inert fillers, and combinations thereof (Labib, e.g., 0091). Labib teaches the composition having a similar amount of polyethylene glycol, e.g., about 12-20% of the composition. Labib, e.g., example 3 teaches a composition having about 12.99% PEG by mass (5.53/42.55x100). Labib, e.g., example 11, teaches a composition having about 20% by mass PEG. Consider, e.g., that 50% of 12% is 6 percent and 200 percent of 12 percent is 24%. Both 6 percent and 24 percent are within the range of less than about 25%. 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). MPEP 2144.05.
Applicable to claim 46: Labib suggests minocycline and rifampin are suitable to form a solid solution to at least some extent in the material (Labib, e.g., 0094, 0072-0075, 0119, and example 3).
Applicable to claim 55: Labib teaches wherein at least one said bioactive agent has less than about 5 percent weight loss at a temperature of 200° C (Labib, e.g., claim 1 and 0096). Thus, there exists a temperature according to claim 22 in the prior art.
Applicable to claims 56-57: Labib teaches the composition formed into a part of a medical device such as a catheter (Labib, e.g., 0050, 0110, and claim 7).
Applicable to claims 60-61: Labib teaches wherein the thermoplastic material is polyurethane or polysilicone or ethylene-vinylacetate copolymer (Labib, e.g., claim 11). Thus, the skilled artisan would have found it obvious to substitute polyurethane or polysilicone for ethylene vinyl acetate copolymer in the exemplified compositions.
Applicable to claims 63: Labib teaches wherein the bioactive powder is micron sized, i.e., micronized powder (Labib, e.g., 0108).
Accordingly, the subject matter of claims 29, 30-31, 42-46, 55-57, 60-61, and 63 would have been prima facie obvious before the effective filing date of the presently claimed invention, absent evidence to the contrary.
Claims 29 and 65 are rejected under 35 U.S.C. 103 as being unpatentable over Labib, US 20110300202 in view of Buevich, US 20140046350 as applied to claims 29, 30-31, 42-46, 55-57, 60-61, and 63 above, and further in view of Darouiche, US 5624704.
The combined teachings of Labib and Buevich teach a composition according to claim 29 as enumerated above. The combined teachings of Labib and Buevich teach a composition comprising a base polymer (host polymer), e.g., ethylene vinyl acetate (EVA), polyethylene glycol (at least one release modifying material) mixed together with the base polymer and making up a minor proportion of the composition, and further comprising a combination antibiotic containing rifampin and minocycline. The combined teachings of Labib and Buevich teach minocycline present as powder or particles in the composition but do not expressly teach wherein rifampin is in crystalline form.
Darouiche teaches minocycline and rifampin are commercially available as crystalline powders (Darouiche, e.g., c5:25-46). Applicable to claim 65: Darouiche teaches crystalline antibiotics (Darouiche, e.g., c5:25-46).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the presently claimed invention to modify a composition suggested by the combined teachings of Labib and Buevich by incorporating rifampin in the form of crystals with a reasonable expectation of success. The skilled artisan would have been motivated to incorporate minocycline in crystalline form for convenience since minocycline is commercially available in crystalline form. The skilled would have had a reasonable expectation of success because Labib teaches preparing the material so that the drug is present in particulate form without fully melting.
Accordingly, the subject matter of claims 29 and 65 would have been prima facie obvious before the effective filing date of the presently claimed invention, absent evidence to the contrary.
Claims 29 and 56-59 are rejected under 35 U.S.C. 103 as being unpatentable over Labib, US 20110300202 in view of Buevich, US 20140046350 as applied to claims 29, 30-31, 42-46, 55-57, 60-61, and 63 above, and further in view of Labib, US 20180200185 (Labib 185).
The combined teachings of Labib and Buevich teach a composition according to claim 29 as enumerated above. The combined teachings of Labib and Buevich teach a composition comprising a base polymer (host polymer), e.g., ethylene vinyl acetate (EVA), polyethylene glycol (at least one release modifying material), and further comprising a combination antibiotic containing rifampin and minocycline in the form of discrete particles, and wherein the composition is formed by melt processing.
Labib further teaches the composition may be formed into useful articles by standard methods, e.g., extrusion, compression, or injection molding (Labib, e.g., 0022), and useful in articles such as catheters, shunts, drains, implants, sutures, meshes, stents (Labib, e.g., 0110 and claim 16).
The combined teachings of Labib and Darouiche do not expressly teach the composition formed into a sleeve.
Labib 185 teaches constructs which elute antibiotics, e.g., a first and second antibiotic (Labib 185, e.g., claim 19), in the form of a sleeve for use with devices which pass through the skin such as pins or catheters (Labib 185, e.g., 0548-0550).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the presently claimed invention to modify a composition useful for eluting antibiotics suggested by Labib and Buevich by forming the polymeric composition into a sleeve configured for use with a fixation pin or catheter as suggested by Labib 185 with a reasonable expectation of success. Since Labib and Buevich teach an antibiotic eluting composition which may be formed into useful articles by standard polymer processing methods, the skilled artisan would have found it obvious to form the antibiotic eluting composition into a sleeve known from Labib 185 with a reasonable expectation of success. The skilled artisan would have seen this modification as a selection of a known material based on its suitability for its intended use. See MPEP 2144.07. The skilled artisan would have been motivated to make this modification to enable compositions known from Labib and Buevich to reduce infection complications related to the use of fixation pins and catheters as taught by Labib 185. The skilled artisan would have had a reasonable expectation of success because Labib teaches the compositions may be formed into articles using known processing techniques and because Labib teaches the compositions may be used with implants and catheters.
Accordingly, the subject matter of claims 29 and 56-59 would have been prima facie obvious before the effective filing date of the presently claimed invention, absent evidence to the contrary.
Claims 29 and 64-65 are rejected under 35 U.S.C. 103 as being unpatentable over Labib, US 20110300202 in view of Buevich, US 20140046350 as applied to claims 29, 30-31, 42-46, 55-57, 60-61, and 63 above, and further in view of Henwood, Drug Dev and Ind Pharm, 27, 2001.
The combined teachings of Labib and Buevich teach a composition according to claim 29, wherein the first and second drug are present in the composition in the form of particles. Labib teaches the particles having a particle size distribution, wherein the particles of bioactive agent are prepared by grinding or milling or prepared by agglomeration (Labib, e.g., 0107).
The combined teachings of Labib and Buevich do not expressly teach wherein the rifampin is in a form of plate-like particles. The combined teachings of Labib and Buevich do not expressly teach wherein the rifampin is in a form of crystalline structures.
Henwood teaches plate like crystals of rifampin were known and effective for antibacterial activity (Henwood, e.g., Abstract and pg. 1020, crystal morphology).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the presently claimed invention to employ crystalline rifampin having a plate like morphology in compositions suggested by the combined teachings of Labib and Buevich with a reasonable expectation of success. The skilled artisan would have seen this modification as the selection of a known rifampin form to predictably achieve the antibacterial activity desired from Buevich. See MPEP 2144.07. The skilled artisan would have had a reasonable expectation of success because Labib teaches incorporating at least one antibacterial agent in solid form into the composition using melt processing.
Accordingly, the subject matter of claims 29 and 64-65 would have been prima facie obvious before the effective filing date of the presently claimed invention, absent evidence to the contrary.
Conclusion
No claim is allowed.
Claim 33 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Neither Labib reference of record teaches where said second release modifying material comprises polycaprolactone. On the current record Natu was cited for teaching polycaprolactone as a release modifying material for ethylene vinyl acetate host polymer. However, claim 33 requires a combination of melt processable host polymer, polyethylene glycol, polycaprolactone, minocycline and rifampin in particle form. The current specification, e.g., Table 8, blend 8 compared with blend 11 show results both with PCL (blend 8) and without PCL (blend 11). According to table 8, the blend with PCL releases more minocycline and rifampin than the blend without PCL. The skilled artisan could not have predicted that the inclusion of PCL would result in increased release of minocycline and rifampin present in amounts within the claimed range as shown even if contemplating the modification of compositions suggested by Labib. Polycaprolactone is relatively hydrophobic compared to polyethylene glycol. While Buevich teaches polymer composition may be used to alter release rate of drug from the composition, the skilled artisan would have likely predicted that the addition of caprolactone would result in decreased release of minocycline and/or rifampin since Buevich suggests polymers with limited water uptake, i.e., more hydrophobic, will retard release of agents (Buevich, e.g., 0049). Thus, the subject matter of claim 33 is commensurate in scope with materials having properties which could not have been predicted by the skilled artisan before the effective filing date of the presently claimed invention and this evidence outweighs the evidence of obviousness for the subject matter of claim 33.
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.
Correspondence
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/WILLIAM CRAIGO/Examiner, Art Unit 1615
/SUSAN T TRAN/Primary Examiner, Art Unit 1615
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