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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 08/12/2026 has been entered.
Status of Claims
Claims 94-122 are pending. Claims 95-122 are withdrawn.
Priority
Instant application 17/290,510, filed 04/30/2021 claims priority as follows:
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Response to Amendment/Arguments
The request for continued examination filed 08/12/2026 has been entered.
Claim Rejections - 35 USC § 103 - Maintained
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim 94 is rejected under 35 U.S.C. 103 as being unpatentable over Han (US 20140323446 A1; published 30 October 2014; cited previously) in view of Walpole (“The Weight of Nations: An Estimation of Adult Human Biomass.” BMC Public Health, vol. 12, no. 1, June 2012, p. 439. BioMed Central; cited previously) and further in view of Crass (Antimicrobial Agents and Chemotherapy, vol. 61, no. 4, Apr. 2017, pp. e02329-16; cited previously).
Applicant’s Invention
Applicant’s invention is drawn to a method of treating bacterial infections in a mammal, comprising administering to said mammal zileuton and a nephrotoxicity-inducing antibiotic, wherein the elected nephrotoxicity-inducing antibiotic is polymyxin B. In particular, claim 94 requires administering an effective amount of zileuton for reducing renal injury induced by the antibiotic.
Teachings of Han
Han teaches uses of zileuton for the treatment of nasal polyps in cystic fibrosis (CF) patients (see abstract). In particular, Han discloses an association between the presence of nasal polyps and Pseudomonas aeruginosa infections in CF patients (see para. 0005): “This association between Pseudomonas respiratory colonization and the presence of nasal polyposis may contribute to the higher annual rates of cystic fibrosis-related acute exacerbations and hospitalizations observed in some clinical trials in CF patients with polyposis in comparison to CF patients without polyposis.” Additionally, Han teaches administering zileuton to patients having CF and a Pseudomonas infection comprising administering to the patient an effective amount of zileuton (see claims 25 and 26). A patient is a human having cystic fibrosis (see para. 0034).
Instant claim 94 additionally requires that the “effective amount of zileuton is between about 0.5 mg/kg to about 180 mg/kg). Han discloses daily doses of zileuton in paras. [0015] and [0036], providing that zileuton can be administered at a dose of about 450 mg to about 2400 mg per day. Note that Hans doses are disclosed as mg per day whereas the instant claims recite mg per kg bodyweight.
However, Walpole is relied upon to show that the average body mass of humans is 62 kg (see pg. 3, Table 3). A person having ordinary skill would have therefore recognized that the dosage range of Han, adjusted for the average human body mass, comprises approximately 7.3 mg/kg (450 mg / 62 kg) to 38.7 mg/kg (2400 mg / 62 kg), which reads on the recited range.
Differences between Han and the instant claims
Han fails to disclose administering zileuton in combination with polymyxin B.
Teachings of Crass
Crass discloses a study exploring nephrotoxicity in human patients with or without CF treated with polymyxin B or colistin. In particular, Crass discloses that despite clinical use beginning over half a century ago, the polymyxin class of antibiotics, which comprises polymyxin B and colistin, retains activity against many multidrug-resistant (MDR) bacteria, including Pseudomonas aeruginosa (see pg. 1, para. 1). Further, Crass discloses that patients with CF have a high burden of MDR infections and may require treatment with polymyxins (see pg. 2, para. 2). Crass is relied upon for its teaching that polymyxin B has been and can be administered to CF patients to treat bacterial infections, including infections arising from Pseudomonas. Crass discloses doses of polymyxin B in Table 2 at page 3.
Instant claim 94 additionally requires that the “effective amount of the…antibiotic is between about 1.0 mg/kg to about 25 mg/kg”. Crass discloses administering polymyxin B (PMB) in a dose of 1.6 mg/kg to cystic fibrosis patients, which reads on the recited range. See Table 2 of Crass.
Differences between Crass and the instant claims
Crass fails to disclose administering polymyxin B in combination with zileuton.
Finding of prima facie obviousness
The Supreme Court in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. See MPEP 2143.
Examples of rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Applying KSR rationale (A), it would have been prima facie obvious to administer a combination of zileuton taught by Han and polymyxin B taught by Crass to treat patients having a bacterial infection, such as CF patients having a Pseudomonas infection. Each of the elements (zileuton, polymyxin B, and doses for each reading on the recited ranges) were taught in the prior art for administration to CF patients with bacterial infections. A person having ordinary skill in the art could have co-administered zileuton and polymyxin B in the doses taught by the prior art to a patient with a reasonable expectation that the combination would treat the bacterial infection in the patient, because both elements are taught for that purpose in the prior art.
It has been held that “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted).
Response to Arguments
In the Remarks filed 05/16/2024, Applicant argued that:
(a) neither of the cited references teach or suggest an effective amount of zileuton for reducing renal injury induced by a nephrotoxicity- or neurotoxicity-inducing antibiotic;
(b) the dosages of zileuton referred to in Han are “much higher than the doses included in the claimed subject matter” and are not based on the body weight of the patient.
Applicant's arguments have been fully considered but they are not persuasive. In response to the argument (a) that neither of the cited references teach or suggest an effective amount of zileuton for reducing renal injury induced by a nephrotoxicity- or neurotoxicity-inducing antibiotic, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). See also MPEP 2145 II in this regard:
“Mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. In re Wiseman, 596 F.2d 1019, 201 USPQ 658 (CCPA 1979) (Claims were directed to grooved carbon disc brakes wherein the grooves were provided to vent steam or vapor during a braking action. A prior art reference taught noncarbon disc brakes which were grooved for the purpose of cooling the faces of the braking members and eliminating dust. The court held the prior art references when combined would overcome the problems of dust and overheating solved by the prior art and would inherently overcome the steam or vapor cause of the problem relied upon for patentability by applicants. Granting a patent on the discovery of an unknown but inherent function (here venting steam or vapor) "would remove from the public that which is in the public domain by virtue of its inclusion in, or obviousness from, the prior art." 596 F.2d at 1022, 201 USPQ at 661.); In re Baxter Travenol Labs., 952 F.2d 388, 21 USPQ2d 1281 (Fed. Cir. 1991) (Appellant argued that the presence of DEHP as the plasticizer in a blood collection bag unexpectedly suppressed hemolysis and therefore rebutted any prima facie showing of obviousness. However, the closest prior art utilizing a DEHP plasticized blood collection bag inherently achieved same result, although this fact was unknown in the prior art.).”
In the instant case, both Han and Crass each teach effective amounts (reading on the claimed ranges) of zileuton and polymyxin B, respectively. A skilled artisan would have administered the combination of zileuton and polymyxin B in the amounts taught by Han and Crass to a patient population having a bacterial infection and CF, and would have been motivated to do so in view of the benefits for administering each agent taught by Han and Crass discussed above. The reduction of renal injury is an advantage which would flow naturally from administering both compounds to the same patient population as the instant claims (mammals with a bacterial infection).
In response to the argument (b) that the dosages of zileuton referred to in Han are “much higher than the doses included in the claimed subject matter”, please note that when adjusted for an average human body weight of 62 kg (taught by Walpole), the dosage range in Han comprises approximately 7.3 mg/kg (450 mg / 62 kg) to 38.7 mg/kg (2400 mg / 62 kg), which reads on the recited range.
Each of the elements (zileuton, polymyxin B, and effective doses for each) were taught in the prior art for administration to CF patients with bacterial infections. A person having ordinary skill in the art could have co-administered zileuton and polymyxin B to a patient with a reasonable expectation that the combination would treat the bacterial infection in the patient, because both elements are taught for that purpose in the prior art. The skilled artisan would have been motivated to administer the combination of agents because zileuton is effective for reducing the likelihood of developing nasal polyps in CF patients having a Pseudomonas infection, and polymyxin B is effective for treating Pseudomonas infections.
Conclusion
Claim 94 is rejected. Claims 95-122 are withdrawn.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kyle Nottingham whose telephone number is (571)270-0640. The examiner can normally be reached M-F from 8:30 am - 5:30 pm.
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/K.N./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
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