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 .
Priority
The instant application, filed 03/08/2022, is a national stage entry 371 of PCT/GB2020/052187, filed 09/10/2020. Acknowledgment is made of Applicant's claim for foreign priority based on an application filed in United Kingdom (GB1913068.1) on 09/10/2019. Receipt is acknowledged of certified copies of papers required by 37 CFR § 1.55.
Continued Examination Under 37 CFR § 1.114
A request for continued examination under 37 CFR § 1.114, including the fee set forth in 37 CFR § 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR § 1.114, and the fee set forth in 37 CFR § 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR § 1.114. Applicant's submission filed on December 11, 2025 has been entered.
Amendments and Claim Status
The following amendments filed on 11/17/2025 are acknowledged and entered.
Claims 13, 18, 27 are amended;
Claims 25 and 26 are cancelled;
Claim 28 is added;
Claims 1-12 remain withdrawn from further consideration pursuant to 37 CFR § 1.142(b), as being drawn to a non-elected invention and species;
Claims 1-24, 27, and 28 are pending and are under prosecution.
Information Disclosure Statement
The Information Disclosure Statement filed on 11/25/2025 is acknowledged and found to be in compliance with the provisions of 37 CFR § 1.97. Accordingly, the information disclosure statements is considered.
Response to arguments
Applicant’s arguments filed 11/17/2025 with respect to the claim objections and claim rejections under 35 U.S.C. §§ 102(a)(1) and 103, as well as the nonstatutory double patenting rejections have been fully considered.
With respect to the rejection of claims 13-23 and 27 under 35 U.S.C. § 102(a)(1) as being anticipated by Chien et al. (Antimicrob Agents Chemother. Vol. 41, No. 8, pages 1765–1769, published August 1 1997, cited on applicant IDS dated 07/11/2022), the amended claims now require the active agents to be provided as a single, unitary formulation. The amendment by applicant is sufficient to remove Chien as prior art with regard to the anticipation of the instant claims. Accordingly, the rejection under 35 U.S.C. § 102(a)(1) is withdrawn. However, the teachings of rejection are hereby applied in a new rejection under 35 U.S.C. § 103, included hereinafter. Furthermore, the amendments made by Applicant, filed 11/17/2025, have necessitated the addition of a new reference to cover the new claim limitations. The arguments made by Applicant are herein addressed as follows.
Applicant argues that amended claim 13 is now limited to a single, unitary, co-formulated composition, and that Chien discloses only separate tablets of zidovudine and fluoroquinolone, thereby rendering the amended claim novel.
Applicant’s argument is unconvincing, because the mere recitation of a single, combined formulation does not confer patentable distinction over the prior art teachings. It is well-established in the pharmaceutical art that combining two known active agents that are already co-administered, into a single dose formulation constitutes a routine formulation choice and represents an obvious design alternative. Wherein the prior art teaches the concurrent administration of two therapeutic agents to the same patient population, the conversion of such a therapy into a unitary formulation would have been obvious to a person of ordinary skill in the art as a matter of convenience and standard of practice, yielding a simpler dosing by reducing pill burden, and thereby improving patient compliance. Applicant has not identified a structural or functional interaction resulting from the instantly claimed combined formulation that is advantageous over the concomitant administration of zidovudine and fluoroquinolone already taught in the prior art by Chien. Accordingly, the amendment to the claims is simply rendered an obvious pharmaceutical practice.
In terms of the amendments to claim 18, Applicant argues that the claim amendments now recite a product according to option (i) or (ii), relating to separate or combined oral dosage forms contained within a blister pack, or formulation that can be administered parenterally. Applicant argues that Chien is silent on both of these limitations, and thus, the teachings are not applicable.
These arguments are unconvincing because, although Chien may not expressly disclose a unitary co-formulated composition, the conversion of separately administered active agents into a single combined formulation constitutes an obvious design choice as stated above. The instantly claimed formulation modifications are routine in the pharmaceutical art and do not require inventive ingenuity. Furthermore, blister packs and parenteral dosage forms are common pharmaceutical product configurations, routinely employed to facilitate control dosing, enhance adherence, and accommodate patients unable to take oral formulations. A person of ordinary skill in the art would have been motivated to apply these well-known dosage forms to the known combination of zidovudine and fluoroquinolone as a matter of routine optimization. The absence of an express disclosure of blister packaging or parenteral administration in Chien does not negate the clear motivation to combine Chien’s teachings with standard pharmaceutical formulation practices.
With respect to the rejection of claims 25 and 26 under 35 U.S.C. § 103 as being unpatentable over Chien, the cancellation of these claims is sufficient to render the rejection moot. Accordingly, the rejection is hereby withdrawn.
With respect to the rejection of claim 24 under 35 U.S.C. § 103 as being unpatentable over Chien, as applied to claims 13-23, and 27, in view of Brewster et al (International Journal of Pharmaceutics Volume 125, Issue 1, pg. 17-30), hereinafter Brewster, and further in view of Wimer (Clinical Therapeutics, Volume 20, Issue 6, pg. 1049-1070, published December 1998), hereinafter Wimer, the amendments made by Applicant, filed 11/17/2025, have necessitated the addition of a new reference to cover the new claim limitations. The arguments made by Applicant are herein addressed as follows.
Applicant argues that Chien does not teach or suggest synergistic antimicrobial activity now required by claims 13 and 18, thereby rendering the claimed combination not obvious.
Applicant’s argument is found unpersuasive because the act of combining two therapeutically active agents whose combination is already disclosed within the prior art, inherently lends itself to additive or synergistic biological activity, particularly where both agents are administered to the same patient population and target overlapping or related clinical conditions. A person of ordinary skill in the art would reasonably expect that the administration of zidovudine and fluoroquinolone will result in at least an additive therapeutic effect, and would have been motivated to explore the combination or enhanced clinical benefit. The explicit disclosure of synergy in the prior art is not required, because the combination with in the prior art itself reasonably suggests advanced or complementary activity. Wherein the prior art already teaches the combination of zidovudine and fluoroquinolone, it is considered obvious by way of routine experimentation to find the optimal concentration of each component in order to elicit the most therapeutic effect. Therefore, Applicant’s reliance on the absence of an express teaching of synergy in the prior art is unavailing.
Applicant further argues that Chien was directed only to pharmacokinetic and safety evaluation of HIV-infected subjects, and did not assess antibacterial efficacy, and therefore does not teach or suggest the claimed synergistic therapeutic benefit.
Applicant’s argument is unconvincing, because obviousness does not require that a reference be directed to the same experimental objective as that of the instant claims. Chien teaches coadministration of zidovudine and levofloxacin to the same patient population, and a person of ordinary skill in the art would reasonably expect the combining known therapeutically active agents to yield additive or enhanced therapeutic effects, regardless of whether the prior art specifically evaluated antibacterial efficacy. The absence of an express antibacterial efficacy study in the prior art does not negate the motivation to combine the agents or the reasonable expectation of success upon doing so. Put simply, levofloxacin is an antibacterial drug. As such, a person of ordinary skill in the art would have been directly motivated to use and evaluate the efficacy of levofloxacin in the bacterial treatment of patient populations explicitly taught to have a compromised immune system (HIV), as taught in the prior art.
Applicant further contends that Chien does not teach or suggest that zidovudine possesses antibacterial activity, or that administration with levofloxacin will confer any therapeutic benefit beyond the individual effects of each agent.
This argument is unconvincing because obviousness does not require that each agent independently possess the same activity, or that the prior art expressly identify the precise therapeutic advantage later relied upon by Applicant. The disclosure by Chien was published early within historical advent of the HIV/AIDS epidemic, wherein much of the research was inherently focused on the safety of combinations of used within a very vulnerable patient population. Nevertheless, the act of combining two known active agents taught to be administered to the same patient population, inherently lends itself to additive or synergistic biological effects, and the skilled artisan would have been motivated to explore such combinations as a matter of routine pharmaceutical practice, in order to achieve the optimal therapeutic effect. Combination therapies are commonly investigated precisely because enhanced effects are expected possibilities. The claims do not recite any limitation that would distinguish the asserted synergy from the predictable results of combining known therapeutic agents, already taught in the prior art.
Applicant asserts that synergy between two active agents is unpredictable, and therefore constitutes a surprising technical effect sufficient to overcome obviousness.
Applicant’s argument is unconvincing, because combination therapies are routinely pursued in the pharmaceutical art, as stated earlier, precisely because enhanced or synergistic effects are expected outcomes of combining known agents, especially when the prior art explicitly teaches their combination. Furthermore, the claims broadly recite “synergistic activity” without requiring any specific mechanistic interaction, quantitive threshold, or compositional feature that produces an unexpected result beyond what would be reasonably expected from combination therapy already taught in the prior art. As such, the alleged synergy represents an unexpected property of the combination, rather than an unexpected technical effect sufficient to rebut a prima facie case of obviousness.
Applicant further argues that it would not have been obvious to formulate zidovudine and levofloxacin as a single combined formulation, because Chien does not teach any therapeutic advantage of coadministration.
Applicant’s argument is unconvincing because a person of ordinary skill in the art would have been motivated to co-formulate the agents, as stated earlier, to achieve well-recognized pharmaceutical objectives, including simplify dosing regimens, reduce pill burden, improving patient compliance, a standard administration practice. The conversion of a known multiagent regimen into a single dosage form constitutes an obvious design choice and routine optimization within the level of ordinary skill in the art. Furthermore, no additional data has been provided or discussed by Applicant to demonstrate any unexpected results of co-formulating the agents into a unitary composition that would not be achieved by the concomitant administration of the individual components of the composition, disclosed in the prior art by Chien. According to MPEP §716.02 (b) (I),
The evidence relied upon should establish "that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance." Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992) (Mere conclusions in appellants’ brief that the claimed polymer had an unexpectedly increased impact strength "are not entitled to the weight of conclusions accompanying the evidence, either in the specification or in a declaration."); Ex parte C, 27 USPQ2d 1492 (Bd. Pat. App. & Inter. 1992) (Applicant alleged unexpected results with regard to the claimed soybean plant, however there was no basis for judging the practical significance of data with regard to maturity date, flowering date, flower color, or height of the plant.). See also In re Nolan, 553 F.2d 1261, 1267, 193 USPQ 641, 645 (CCPA 1977) and In re Eli Lilly, 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) as discussed in MPEP § 716.02(c)
Thus, the burden is on the applicant to demonstrate that any asserted unexpected results are both significant and unexpected, and that they are directly attributable to the claimed invention. Importantly, the Applicant must provide a comparison with the closest prior art. Examiner has identified the art of Chien as prior art which closely resembles the teachings of the instant claims. However, no such comparison between the concomitant administration taught by the prior art and the instantly claimed co-administration has been presented by Applicant. Mere attorney argument or conclusory statements without adequate supporting evidence are insufficient to rebut a prima facie case of obviousness.
Applicant further contends that the prior art provides no motivation to co-formulate the agents in a blister pack, or formulate the combination for parenteral administration, and that neither Brewster nor Wimer suggest synergy.
Applicant’s argument is unpersuasive because blister packaging is a conventional pharmaceutical configuration routinely employed to control dosing schedules, enhance adherence, and facilitate administration. A person of ordinary skill in the art would be motivated to apply such packaging to the known combination as a matter of routine pharmaceutical practice, independent of any asserted therapeutic advantage. Furthermore, regarding the formulation of a combination for parenteral administration, Brewster teaches the parenteral administration of zidovudine, and Wimer teaches parenteral administration of levofloxacin for patients unable to take oral formulations. These teachings expressly motivate a person of ordinary skill in the art to provide alternative routes of administration for the already known combination, and an express teaching of synergy is not required to establish obviousness. The application of known routes of administration to known active agents constitute a routine optimization, yielding predictable results.
The extensive amendments to the claims have necessitated the amendment of the original rejection, which is not overcome by amendment, and is hereby maintained for the reasons set forth above.
With respect to the nonstatutory double patenting rejections of claim 13-27 as being unpatentable over claims 18, 20-28, 30 and 31 of copending Application No. 17/768,669 (U.S. Publication No. 2024/0197767 A1) in view of Kim et al. (Ann Lab Med 2017;37:231-239, published May 1, 2017), hereinafter Kim, claims 1-7, 15, and 16 of U.S. Patent No. 11,951,119 in view of Kim, claims 1-5, and 10-13 of U.S. Patent No. 10,888,575 in view of Kim, and claims 3-5 of U.S. Patent No. 9,757,427 in view of Kim, the claim amendments and arguments made by Applicant are insufficient to overcome the rejection. The arguments made by Applicant are herein addressed as follows.
Applicant argues that the pending claims are patentably distinct from the claims of the co-pending and patent applications because the present claims are limited to combinations exhibiting synergistic activity.
This argument is unconvincing because the recitation of synergy as a functional result does not impart patentable distinctness over the claims of the co-pending applications. The pending claims do not require any specific structural interaction, mechanistic limitation, a quantitative synergy threshold that would meaningfully distinguish the presently claimed combinations from those previously claimed rather, the claims broadly encompass combinations intended to achieve synergy, which is an expected objective of combination therapy and does not constitute a distinct invention for the purposes of overcoming an obviousness-type double patenting rejection.
Applicant further argues that the antibiotics disclosed in the co-pending applications are not suitable equivalents of fluoroquinolones because they belong to different antibiotic classes.
Applicant’s argument is unconvincing because differences in chemical class, structure, the mechanisms of action do not, by themselves, establish patentable distinctness where the antibiotics are used for the same therapeutic purpose, and achieve the same intended result when combined with zidovudine. For the purposes of obviousness-type double patenting, antibiotics that are known alternatives for treating bacterial infections, and are combined with the same primary agent are considered suitable equivalents, absent a claim recited limitation establishing a materially different limitation. The present claims do not include such limitation.
Applicant further argues that, due to the inherent unpredictability of drug synergy in the potential of antagonism, it would not have been obvious to substitute antibiotics to arrive at the present claims.
This argument is unconvincing because combination therapies are routinely explored and pharmaceutical arts, precisely because enhanced or synergistic effects are expected possibilities, notwithstanding the potential for antagonism. The possibility that some combinations may be less effective does not negate the obviousness of selecting alternative antibiotics to achieve the same intended therapeutic outcome. The claims do not require a specific, nonobvious interaction that would distinguish the present combinations from those claimed in the co-pending and patented cases.
As such, the nonstatutory double patenting rejections are hereby maintained.
Thus, all arguments presented by Applicants have been addressed and are found unpersuasive for the reasons presented herein and in the previous non-final rejection. Applicants are reminded that “attorney argument [is] not the kind of factual evidence that is required to rebut a prima facie case of obviousness.” In re Geisler, 116 F.3d 1465, 1470 (Fed. Cir. 1997). The arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965).
New claim 28 is being rejected on the same grounds under 35 U.S.C. § 103 and is subject to the nonstatutory double patenting rejections as detailed below.
Claim Rejections – 35 U.S.C. § 103
The text of those sections of title 35, U.S. Code not included in this action can be found in the prior Office action.
Claims 13-23 are rejected under 35 U.S.C. § 103 as being unpatentable over Chien et al. (Antimicrob Agents Chemother. Vol. 41, No. 8, pages 1765–1769, published August 1 1997, cited on applicant IDS), hereinafter Chien, in view of Moon and Oh (Journal of Pharmaceutical Investigation, Volume 46, pages 615-631, published November 19, 2016).
The instant claims are drawn to a pharmaceutical composition comprising zidovudine and a fluoroquinolone, elected in the instant case to be levofloxacin, provided in a single combined formulation, wherein the components are present in the composition in amounts effective to elicit synergistic activity. The claims are further draw to a product which is either a blister pack comprising dosage forms containing zidovudine and fluoroquinolone, elected to be levofloxacin, in separate or single formulations, or a formulation comprising zidovudine and fluoroquinolone, elected to be levofloxacin, in separate compositions or a combined composition.
Chien teaches the concomitant administration of levofloxacin and zidovudine for use in the treatment of a microbial infection (HIV) (title). Chien discloses an oral tablet form, and pharmaceutical regimens and products wherein zidovudine and levofloxacin are administered together (Abstract, page 1766 study design) which meets the limitations of the instant claims, including those directed to compositions, tablets and unit dosage forms containing separate or unitary formulations for oral administration. Levofloxacin is administered as a tablet, which necessarily includes pharmaceutically acceptable excipients typical of oral dosage forms (page 1766).
Regarding claims 13-23, the teachings of Chien render obvious the instant claims by teaching the simultaneous administration of zidovudine and levofloxacin to patients in the form of oral tablets with dosage forms containing pharmaceutically acceptable carriers or excipients. Within the disclosure, both drugs are administered together as a part of a pharmaceutical regimen, inherently meeting the limitations of a pharmaceutical composition or product containing both agents.
Regarding claim 13, Chien fails to teach a single combined formulation comprising zidovudine and levofloxacin provided in amounts effective to provide synergistic activity against microbial infection.
The deficiencies of Chien are remedied by Moon and Oh, who teach that the combination of multidrug components into a single formulation will increase patient compliance and yield better treatment outcomes (Abstract, Table 2). Combination effects known to be elicited from unitary formations are taught to affect the same pharmacodynamic end-point with different mechanisms and contributing to additive or synergistic effects on reduction of disease severity and risk (page 618, Table 2).
Wherein the prior art teaches the concurrent administration of two therapeutic agents to the same patient population, the conversion of such a therapy into a unitary formulation would have been obvious to a person of ordinary skill in the art as a matter of convenience and standard of practice following the teachings of Moon and Oh, yielding a simpler dosing by reducing pill burden, and thereby improving patient compliance (Abstract, pages 615-619). Furthermore, beyond the teachings of Moon and Oh, the act of combining two therapeutically active agents whose combination is already disclosed within the prior art, inherently lends itself to additive or synergistic biological activity, particularly where both agents are administered to the same patient population and target overlapping or related clinical conditions. A person of ordinary skill in the art would reasonably expect that the administration of zidovudine and fluoroquinolone will result in at least an additive therapeutic effect although not inherently taught in the reference, and would have been motivated to further explore their combination in appropriate ratios to elicit enhanced clinical benefit in a unitary, synergistic formulation.
Further regarding claim 13, the dosage regimens disclosed in the prior art overlap with the concentration ranges at which synergistic effects are alleged in the instant specification (see pages 29-31, example 2 of the instant specification). More specifically, the prior art study administers zidovudine at 100 mg doses up to a maximum of 500mg/day with levofloxacin at approximately 350 mg (page 1766 of Chien), overlapping with the dosages broadly claimed within the instant application (see example 2, instant specification). As such, the overlapping amounts of zidovudine and levofloxacin taught within the prior art would be expected to provide a synergistic combination.
For clarity of the record, wherein dosages detailed in the instant specification are given in terms of plasma concentration in mg/L and the dosages in the prior art are taught as a mass given in mg: a dose administered in mg corresponds to a systemic concentration in mg/L upon the distribution of the dose into the body’s total volume of distribution, yielding a plasma concentration. For example, a 300-500 mg oral dose of a small molecule drug with the typical volume of distribution on the order of tens to hundreds of liters of blood plasma would reasonably be expected to produce a plasma concentration in the low mg/L range. This overlap in concentration is further evidenced by Tables 2 and 4 and Figure 4 of Chien, which detail plasma concentrations in mg/mL, wherein 1mg/mL = 1 mg/L. More directly, the Cmax values of levofloxacin within the prior art correspond to 3.82-7.06 mg/mL, which overlap with the concentrations of levofloxacin detailed in example 2 of the instant specification, spanning the 4-8 mg/L concentrations tested within the dilution series shown on page 31 of the instant specification. Furthermore, Applicant claims broad concentration ranges which allegedly result in synergy, deemed obvious as a routine optimization of the ratio already taught within the prior art by Chien. The courts have found that,
“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, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP § 2144.05 II.
Therefore, the instantly claimed synergistic activity resulting from the broadly claimed concentrations of zidovudine and levofloxacin merely represents a routine optimization of the ratio of zidovudine and fluoroquinolone already disclosed in the cited prior art by Chien. The prior art already teaches the combination of zidovudine and fluoroquinolone, and it is considered obvious by way of routine experimentation to find the optimal concentration of each component in order to elicit the most therapeutic effect.
Regarding claim 18, Chien does not specifically teach the active ingredients in a combination product. However, the courts have determined that the combinations of elements known to be suitable for an intended purpose is deemed obvious.
The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945) (Claims to a printing ink comprising a solvent having the vapor pressure characteristics of butyl carbitol so that the ink would not dry at room temperature but would dry quickly upon heating were held invalid over a reference teaching a printing ink made with a different solvent that was nonvolatile at room temperature but highly volatile when heated in view of an article which taught the desired boiling point and vapor pressure characteristics of a solvent for printing inks and a catalog teaching the boiling point and vapor pressure characteristics of butyl carbitol.) See also In re Leshin, 277 F.2d 197, 125 USPQ 416 (CCPA 1960) (selection of a known plastic to make a container of a type made of plastics prior to the invention was held to be obvious); Ryco, Inc. v. Ag-Bag Corp., 857 F.2d 1418, 8 USPQ2d 1323 (Fed. Cir. 1988) (Claimed agricultural bagging machine, which differed from a prior art machine only in that the brake means were hydraulically operated rather than mechanically operated, was held to be obvious over the prior art machine in view of references which disclosed hydraulic brakes for performing the same function, albeit in a different environment.)
According to Chien, zidovudine is known in the art as antiretroviral agent for treating HIV infection, and levofloxacin is known for treating bacterial infections, including those encountered in immunocompromised patients. Therefore, according to MPEP § 2144.07, the combination of zidovudine and levofloxacin in a product would be an obvious solution for providing both therapies to HIV-infected individuals at risk for bacterial infection, as demonstrated by the prior art, which teaches the coadministration of both drugs in the same patient population (Abstract). A person of ordinary skill in the art prior to the effective filing date of the instant application, following the teachings of Chien, would have been motivated to combine zidovudine and levofloxacin in a pack in order to facilitate patient compliance, ensure proper co-administration, and provide convenient access to both agents as part of the treatment regimen for HIV-infected patients who may require concurrent antibacterial therapy. As such, claim 18 is rendered obvious in view of the cited prior art teachings.
In the interest of brevity, the teachings are individually applied to each claim, and the claims herein stand rejected.
Claims 13-23, 24, and 28 are rejected under 35 U.S.C. § 103 as being unpatentable over Chien et al. (Antimicrob Agents Chemother. Vol. 41, No. 8, pages 1765–1769, published August 1 1997, cited on applicant IDS), hereinafter Chien, as applied to claims 13-23 above, in view of Brewster et al (International Journal of Pharmaceutics, Volume 125, Issue 1, pg. 17-30), hereinafter Brewster, and further in view of Wimer (Clinical Therapeutics, Volume 20, Issue 6, pg. 1049-1070, published December 1998).
The claims are further drawn to a pharmaceutical composition comprising zidovudine and levofloxacin, in dosage forms suitable for parenteral administration (claim 24). Claim 28 is drawn to a product comprising zidovudine and levofloxacin in either separate or single combined formulations to be administered parenterally.
Chien is as set forth above.
Chien fails to teach a pharmaceutical composition suitable for parenteral administration.
However, Chien acknowledges “gastrointestinal problem(s) which could affect absorption of the study medication” as a basis for exclusion from the study (page 1766). Thus, Chien expressly recognizes that gastrointestinal (GI) complications could limit absorption of the study drugs, providing motivation to seek alternative routes of administration such as parenteral, which bypass the GI system, avoiding GI dysfunction altogether.
The deficiencies of Chien are remedied by Brewster, who describes development of parenteral dosage forms of zidovudine, and the resulting improved brain levels and bioavailability of the drug (Abstract).
The deficiencies of Chien are further remedied by Wimer, who teaches the clinical utility of intravenous (parenteral) levofloxacin for patients unable to use oral formulations (Abstract, page 1050).
Accordingly, prior to the effective filing date of the instant claims, a person of ordinary skill in the art would have recognized, based on Chien’s explicit statement regarding the impact of GI dysfunction on drug absorption, the need for alternative non-oral administration routes in certain patient populations. Therefore, a person of ordinary skill in the art prior to the effective filing date of the claimed invention would have found it obvious to modify the oral coadministration regimen of zidovudine and levofloxacin to provide for a pharmaceutical composition and methods suitable for parenteral administration since both Brewster and Wimer teach that zidovudine and levofloxacin, respectively, are available and effective in intravenous formulations. The motivation to make this modification arises directly from Chien’s recognition that patient populations are not universally able to absorb oral formulations. Providing an alternative route of administration would increase the population of patients to which the therapeutic compositions could be administered to.
Thus, claims the claims are rendered obvious in view of the cited prior art teachings.
Claims 13-23, and 27 are rejected under 35 U.S.C. § 103 as being unpatentable over Chien et al. (Antimicrob Agents Chemother. Vol. 41, No. 8, pages 1765–1769, published August 1 1997, cited on applicant IDS), hereinafter Chien, in view of Moon and Oh (see earlier citation), as applied to claims 13-23 above, and further in view of Connor et al. (Bulletin of the World Health Organization, Volume 82, Issue 12, published December 2004), hereinafter Connor.
The claims are further drawn to a product comprising zidovudine and levofloxacin, in the form of a blister pack (claims 18 and 27).
Chien and Moon and Oh are as set forth above.
Neither Chien nor Moon and Oh teach a product in the form of a blister pack.
The deficiencies of Chien and Moon and Oh are remedied by Connor, who teaches that the packaging medication regimens improves adherence (Title, Abstract), well understood in the art as a way to improve patient compliance as taught by Moon and Oh. More specifically, Connor teaches wherein blister packs exhibit significant advantages in storage, handling and preservation of medication. Connor further discloses that blister packs are preferred by staff and users (page 937), improving adherence to medication regimen (Abstract).
Accordingly, prior to the effective filing date of the instant claims, a person of ordinary skill in the art would have recognized, that implementing a blister pack or unit dose packaging for levofloxacin and zidovudine would ensure accurate, coordinated, and compliant coadministration of the two agents. Chien discloses a tightly control dosing regimen in which levofloxacin is administered concomitantly with zidovudine. Given the demonstrated safety within the disclosure by Chien, lack of drug-drug interaction, and predictable pharmacokinetic behavior under repeated dosing, the person of ordinary skill in the art would recognize the packaging the drugs together in a blister pack would promote dose accuracy, temporal alignment of administration, reduced patient error, and improved adherence as taught by Connor, particularly in HIV-infected patients managing complex multi-day medication regimens. Such packaging would therefore represent an obvious and practical design choice motivated by a need for better patient compliance rather than an inventive leap.
Thus the claims are rendered obvious in view of the cited prior art teachings.
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.
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Claims 13-24, 27, and 28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 18, 20-28, 30 and 31 of copending Application No. 17/768,669 (U.S. Publication No. 2024/0197767 A1) in view of Kim et al. (Ann Lab Med 2017;37:231-239, published May 1, 2017), hereinafter Kim, and further in view of Moon and Oh (see earlier citation). Although the claims at issue are not identical, they are not patentably distinct from each other because the combination of zidovudine with an antibiotic in both the instant application as well as the co-pending application is not patentably distinct. In the instant application, zidovudine is combined with a fluoroquinolone antibiotic. In the copending application, zidovudine is combined with a tetracycline antibiotic. According to Kim, fluoroquinolones and tetracyclines are considered substitutable equivalents, used for the same purpose, i.e., treating bacterial infections (Tables 1 and 2). According to MPEP § 2144.06 (II), art-recognized equivalents substituted for the same purpose are rendered obvious. The courts have stated:
In order to rely on equivalence as a rationale supporting an obviousness rejection, the equivalency must be recognized in the prior art, and cannot be based on applicant’s disclosure or the mere fact that the components at issue are functional or mechanical equivalents. In re Ruff, 256 F.2d 590, 118 USPQ 340 (CCPA 1958) (The mere fact that components are claimed as members of a Markush group cannot be relied upon to establish the equivalency of these components. However, an applicant’s expressed recognition of an art-recognized or obvious equivalent may be used to refute an argument that such equivalency does not exist.); Smith v. Hayashi, 209 USPQ 754 (Bd. of Pat. Inter. 1980) (The mere fact that phthalocyanine and selenium function as equivalent photoconductors in the claimed environment was not sufficient to establish that one would have been obvious over the other. However, there was evidence that both phthalocyanine and selenium were known photoconductors in the art of electrophotography. "This, in our view, presents strong evidence of obviousness in substituting one for the other in an electrophotographic environment as a photoconductor." 209 USPQ at 759.). An express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982).
Therefore, it is considered prima facie obvious to substitute fluoroquinolone for the tetracycline in the copending application and arrive at the instant invention. Kim presents these agents as interchangeable alternatives for use in treating bacterial infections. For the purposes of obviousness-type double patenting, antibiotics that are known alternatives for treating bacterial infections, and are combined with the same primary agent are considered suitable equivalents, absent a claim recited limitation establishing a materially different limitation. In the absence of any criticality or limitation to a particular antibiotic or evidence of unexpected results the combinations now claimed, it would have been obvious to try substituting any one of the known fluoroquinolone antibiotics taught by can to arrive at the instantly claimed compositions/products. Furthermore, wherein the copending application teaches the concurrent administration of two therapeutic agents to the same patient population, the conversion of such a therapy into a unitary formulation would have been obvious to a person of ordinary skill in the art as a matter of convenience and standard of practice, yielding a simpler dosing by reducing pill burden, and thereby improving patient compliance, as taught by Moon and Oh (Abstract). Finally, wherein the instant claims are drawn to concentrations which exhibit synergistic activity against microbial, it is considered prima facie obvious by way of routine experimentation to find the optimal concentration of each component in order to elicit the most therapeutic effect, according to MPEP § 2144.05 II.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 13-24, 27, and 28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 15, and 16 of U.S. Patent No. 11,951,119 in view of Kim (see earlier citation), and further in view of Moon and Oh (see earlier citation). Although the claims at issue are not identical, they are not patentably distinct from each other because the combination of zidovudine with an antibiotic in both the instant application as well as the patent is not patentably distinct. In the instant application, zidovudine is combined with a fluoroquinolone antibiotic. In the patented case, zidovudine is combined with mecillinam (penicillin antibiotic), cephalexin (cephalosporin antibiotic) and faropenem (carbapenem antibiotic). According to Kim, fluoroquinolones, penicillin, cephalosporins, and carbapenem antibiotics are considered substitutable equivalents, used for the same purpose, i.e., treating bacterial infections (Tables 1 and 2). According to MPEP § 2144.06 (II), art-recognized equivalents substituted for the same purpose are rendered obvious. Kim presents these agents as interchangeable alternatives for use in treating bacterial infections. For the purposes of obviousness-type double patenting, antibiotics that are known alternatives for treating bacterial infections, and are combined with the same primary agent are considered suitable equivalents, absent a claim recited limitation establishing a materially different limitation. In the absence of any criticality or limitation to a particular antibiotic or evidence of unexpected results the combinations now claimed, it would have been obvious to try substituting any one of the known fluoroquinolone antibiotics taught by can to arrive at the instantly claimed compositions/products. Therefore, it is considered prima facie obvious to substitute fluoroquinolone for the penicillin, cephalosporins, and carbapenem in the patented case to arrive at the instant claims. Furthermore, wherein the patented case teaches the concurrent administration of two therapeutic agents to the same patient population, the conversion of such a therapy into a unitary formulation would have been obvious to a person of ordinary skill in the art as a matter of convenience and standard of practice, yielding a simpler dosing by reducing pill burden, and thereby improving patient compliance, as taught by Moon and Oh (Abstract). Finally, wherein the instant claims are drawn to concentrations which exhibit synergistic activity against microbial infection, it is considered prima facie obvious by way of routine experimentation to find the optimal concentration of each component in order to elicit the most therapeutic effect, according to MPEP § 2144.05 II.
Claims 13-24, 27, and 28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, and 10-13 of U.S. Patent No. 10,888,575 in view of Kim (see earlier citation), and further in view of Moon and Oh (see earlier citation). Although the claims at issue are not identical, they are not patentably distinct from each other because the combination of zidovudine with an antibiotic in both the instant application as well as the patent is not patentably distinct. In the instant application, zidovudine is combined with a fluoroquinolone antibiotic. In the patent, zidovudine is combined with polymyxin and carbapenem. According to Kim, fluoroquinolones, carbapenem and polymyxin antibiotics are considered substitutable equivalents, used for the same purpose, i.e., treating bacterial infections (Tables 1 and 2, and page 237). Kim presents these agents as interchangeable alternatives for use in treating bacterial infections. For the purposes of obviousness-type double patenting, antibiotics that are known alternatives for treating bacterial infections, and are combined with the same primary agent are considered suitable equivalents, absent a claim recited limitation establishing a materially different limitation. In the absence of any criticality or limitation to a particular antibiotic or evidence of unexpected results the combinations now claimed, it would have been obvious to try substituting any one of the known fluoroquinolone antibiotics taught by can to arrive at the instantly claimed compositions/products. According to MPEP § 2144.06 (II), art-recognized equivalents substituted for the same purpose are rendered obvious. Therefore, it is considered prima facie obvious to substitute fluoroquinolone for carbapenem and polymyxin in the patented case to arrive at the instant invention. Furthermore, wherein the patented case teaches the concurrent administration of two therapeutic agents to the same patient population, the conversion of such a therapy into a unitary formulation would have been obvious to a person of ordinary skill in the art as a matter of convenience and standard of practice, yielding a simpler dosing by reducing pill burden, and thereby improving patient compliance, as taught by Moon and Oh (Abstract). Finally, wherein the instant claims are drawn to concentrations which exhibit synergistic activity against microbial, it is considered prima facie obvious by way of routine experimentation to find the optimal concentration of each component in order to elicit the most therapeutic effect, according to MPEP § 2144.05 II.
Claims 13-24, 27, and 28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 3-5 of U.S. Patent No. 9,757,427 in view of Kim (see earlier citation) and further in view of Moon and Oh (see earlier citation). Although the claims at issue are not identical, they are not patentably distinct from each other because the combination of zidovudine with an antibiotic in both the instant application as well as the co-pending application is not patentably distinct. In the instant application, zidovudine is combined with a fluoroquinolone antibiotic. In the patent, zidovudine is combined with polymyxin. According to Kim, fluoroquinolones and polymyxin antibiotics are considered substitutable equivalents, used for the same purpose, i.e., treating bacterial infections (Tables 1 and 2, and page 237). Kim presents these agents as interchangeable alternatives for use in treating bacterial infections. For the purposes of obviousness-type double patenting, antibiotics that are known alternatives for treating bacterial infections, and are combined with the same primary agent are considered suitable equivalents, absent a claim recited limitation establishing a materially different limitation. In the absence of any criticality or limitation to a particular antibiotic or evidence of unexpected results the combinations now claimed, it would have been obvious to try substituting any one of the known fluoroquinolone antibiotics taught by can to arrive at the instantly claimed compositions/products. According to MPEP § 2144.06 (II), art-recognized equivalents substituted for the same purpose are rendered obvious. Therefore, it is considered prima facie obvious to substitute fluoroquinolone for polymyxin in the patented case to arrive at the instant invention. Furthermore, wherein the patented case teaches the concurrent administration of two therapeutic agents to the same patient population, the conversion of such a therapy into a unitary formulation would have been obvious to a person of ordinary skill in the art as a matter of convenience and standard of practice, yielding a simpler dosing by reducing pill burden, and thereby improving patient compliance, as taught by Moon and Oh (Abstract). Finally, wherein the instant claims are drawn to concentrations which exhibit synergistic activity against microbial, it is considered prima facie obvious by way of routine experimentation to find the optimal concentration of each component in order to elicit the most therapeutic effect, according to MPEP § 2144.05 II.
Correspondence
No claim is allowed.
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/SOPHIA P HIRAKIS/Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623