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 present Application, filed October 10 2023 claims priority to U.S. Provisional Patent Application No. 63/414,635, filed October 10, 2022.
Status of the Claims
In the amendment filed July 28, 2026, claims 8-9, 11-19, 34-35, and 40-49 are canceled and new claims 51-52 are added. Claims 1 and 50 are amended. Claims 1-7, 10, 20-33, 36-39, and 50-52 are currently pending.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on July 28, 2026 is acknowledged.
Previous Rejections and/or Objections
Any objections and/or rejections raised in the previous Office Action but not reiterated below are considered to have been withdrawn.
Claim Rejections - 35 USC § 112 – Necessitated by Amendment
The following is a quotation of 35 U.S.C. § 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. § 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 10 is indefinite:
Claim 10 is rejected under 35 U.S.C. § 112(b) or 35 U.S.C. § 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 10 is indefinite for reciting “[t]he method of claim 8.” This recitation lacks antecedent basis, because claim 8 is canceled.
A note on claim interpretation:
Claims 5-7 recite intended results that cannot be given patentable weight in the present circumstances. For example, claim 5 recites the method of claim 1 wherein the treatment achieves microbiological eradication of the infection. “A whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” Minton v. Nat'l Ass'n. of Sec. Dealers, 336 F.3d 1373, 1381 (Fed. Cir. 2003). See also MPEP § 2111.04(I), which makes clear that this rule of claim construction is not limited to clauses marked off by the term “whereby,” but is applicable to functionally equivalent clauses having terms such as “wherein” or other functionally equivalent terms. Claims 6-7 are the same in this respect, as are claims 28-31, which recite the method of claim 1, wherein some functional result is avoided, or does not occur.
Similarly, amended claims 1 and 50 now recite wherein the treatment results in bloodstream clearance of S aureus, wherein clearance is defined as two consecutive days with blood-culture negative assessments. This is likewise an intended result that has no effect on the manner in which the method is performed and, as such, is afforded no patentable weight. Likewise, the element of claim 50 and of claim 52 wherein the treatment results in blood stream clearance within 4 days is an intended result that carries no patentable weight, as it merely describes a desired consequence of performing the method without requiring any change or limitation in the manner in which the method is performed.
Claims 34-35 and 42 recite attribute-dependent dose schedules in which the regimen applied to an individual patient is dependent on attributes such as age, weight, or renal function. The claim is understood as requiring that a single patient is treated according to the schedule, not that a plurality of patients be treated, covering all alternative regimens in the schedule. For example, it is understood that treating a single adolescent of over 50 kg according to a regimen of 500 mg of ceftobiprole every 8 hours would constitute performance of the method of claim 34, and that the claim does not require treating at least 6 pediatric patients to satisfy all recited combinations of age and weight.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-7, 22-23, 27-31,37-39, and 50-52 are anticipated by Hamed:
Claims 1-7, 22-23, 27-31,37-39, and 50-52 rejected under 35 U.S.C. 102(a)(1) as being anticipated by the non-patent publication, Ceftobiprole versus daptomycin in Staphylococcus aureus bacteremia: a novel protocol for a double-blind, Phase III trial, Future Microbiol., 15, pgs. 35-48 (2020) by Hamed et al. (hereinafter, “Hamed”).
With respect to the previous prior art rejections for anticipation and obviousness, Applicant argues that these rejections are overcome by amendment because none of the cite art teaches the feature wherein the treatment results in bloodstream clearance of S. aureus, wherein clearance is defined as two consecutive days with blood-culture-negative assessments (paragraph spanning the bottom of pg. 6 to the top of pg. 7 of Applicant’s Remarks of July 28, 2026). This argument has been fully considered but is not found persuasive. As discussed below, Hamed teaches all method steps of the recited method; i.e. Hamed teaches how the instant method is performed. The outcome of that method as recited, its intended result, does not change the manner in which the method is performed, and therefore does not carry patentable weight. As such, this intended result does not distinguish the method from the method as taught by Hamed. The prior art rejections, as applied to claims still pending, are therefore maintained.
Substantially reiterated rejections:
As noted above and reiterated below, the feature, added via amendment, in which the positively recited method steps result in bloodstream clearance of S. aureus is an intended result of the method and, as such, is not afforded patentable weight.
Claim 1 recites a method of treating a Staphylococcus aureus bloodstream infection (bacteremia) in a patient in need thereof, the method comprising administering ceftobiprole as ceftobiprole medocaril to the patient at a dosage corresponding to of 500 mg of ceftobiprole every 6 hours on days 1 to 8 and 500 mg every 8 hours on days 9 onwards, wherein the patient has right-sided infective endocarditis caused by S. aureus. As noted above, the recitation wherein the treatment results in bloodstream clearance of S. aureus and defines such clearance is an intended result that has no effect on the manner in which the method is performed, and is not afforded patentable weight.
Hamed teaches a Phase III, randomized, double-blind, active-controlled, parallel-group, multicenter, two-part study to establish the efficacy and safety of ceftobiprole compared with daptomycin in the treatment of S. aureus bacteremia (SAB) – Abstract. Hamed teaches the study includes selection of about 390 patients (pg. 38, Study design), half of whom (randomized 1:1) receive ceftobiprole treatment with treatment administered for a duration of 21-28 days (pg. 39, Study procedures), and teaches that the inclusion criteria mandate that the subjects have at least one of four characteristics, one of which is definitive native-valve right-sided infective endocarditis by Modified Duke Criteria (pg. 37, Table 1). Hamed further teaches that the patients receiving ceftobiprole received 500 mg every six hours (q6h) on days 1-8 and then received 500 mg every eight hours (q8h) – [pg. 40, Table 2].
Hamed also teaches that ceftobiprole medocaril is a prodrug of the active drug, ceftobiprole (paragraph spanning the bottom of pg. 35 to the top of pg. 36) and that the title of the study is “A randomized, double-blind, multicenter study to establish the efficacy and safety of ceftobiprole medocaril compared to daptomycin in the treatment of S. aureus bacteremia, including infective endocarditis” (emphasis added), thus indicating that ceftobiprole is in fact administered in the form of the prodrug ceftobiprole medocaril. Hamed thus teaches a method of treating S. aureus bacteremia in a patient comprising administering ceftobiprole medocaril to the patient at 500 mg of ceftobiprole every 6 hours for the first 8 days and administering the same amount every 8 hours thereafter, wherein the patient has right-sided infective endocarditis caused by S. aureus.
With respect to claim 2, Hamed teaches the ceftobiprole is administered for 21-28 days (pg. 38, Study design). With respect to claim 3, “up to 42 days” is understood to include any number of days less than or equal to 42, and so the 21-28 days of administration of Hamed is “up to 42 days.” With respect to claim 4, the enrolled patients in the study of Hamed have “confirmed or suspected complicated SAB” (Abstract).
With respect to claims 5-7 and 28-31, as noted above, these recite intended results which cannot be given patentable weight. As such, these claims are anticipated for the same reason as is claim 1.
With respect to claim 22, Hamed teaches inclusion criteria optionally include SAB in patients undergoing chronic intermittent hemodialysis or peritoneal dialysis (pg. 37, Table 1, item 6). With respect to claim 23, Hamed teaches that randomization (random assignment of subjects to ceftobiprole or daptomycin treatment) is stratified by study site, hemodialysis status, and prior antibacterial treatment use (defined as use of any potentially effective systemic antibacterial treatment within 7 days of randomization - pg. 39, Study procedures). Thus, Hamed indicates that some subjects receiving ceftobiprole have previously received potentially effective treatment with a different antibiotic for the infection.
With respect to claim 27, Hamed teaches inclusion criteria optionally include persistent SAB (pg. 37, Table 1, item 7). With respect to claims 38-39, Hamed teaches that administration of the ceftobiprole medocaril is via two hour intravenous infusion (pg. 39, Study procedures; and pg. 40, Table 2). With respect to claim 37, which recites that the ceftobiprole medocaril is administered via injection, according to a broadest reasonable interpretation, the term “injection” is understood to include intravenous infusion. See, for example, the non-patent publication, intravenous infusion definition, thefreedictionary.com, obtained at the url medical-dictionary.thefreedictionary.com/intravenous+infusion, (copyright updated to 2026) which states that, “[a] push intravenous infusion is the direct injection of medication into a vein through an intravenous line, needle, or catheter;” as well as the non-patent publication, injection definition, thefreedictionary.com, obtained at the url medical-dictionary.thefreedictionary.com/injection, (copyright updated to 2026) which includes the definition of “the forcing of a liquid into a part, as into the subcutaneous tissues, the vascular tree, or an organ.” Because the “injection” of claim 37 encompasses the intravenous infusion of Hamed, claim 37 is likewise anticipated.
Claim 50 recites a method for the treatment of adult patients with S. aureus bacteremia, comprising the method step as recited in claim 1. Claim 50 further recites that the infection is caused by methicillin-susceptible or methicillin-resistant isolates. Since all S. aureus isolates must be either methicillin susceptible or resistant, this element does not limit the claim. Amended claim 50 further recites wherein the treatment results in bloodstream clearance of S. aureus, like claim 1, and also recites wherein said clearance occurs within 4 days. As discussed above, these are intended results that are afforded no patentable weight. As such, claim 50 is substantially the same as claim 1, except that it specifies the patients must be adult. Hamed is applied to claim 50 as to claim 1, and Hamed further teaches that the enrolled patients include 390 adults (pg. 44, Executive summary). Claim 50 is thus anticipated.
With respect to claim 51, Hamed teaches that a required inclusion criterion is that patient have at least one of four listed characteristics, one of which is definitive native-valve right-sided infective endocarditis by Modified Duke Criteria (pg. 37, Table 1). With respect to claim 52, as noted above, the feature that the method of claim 1 results in bloodstream clearance of S. aureus within 4 days is an intended result that does not carry patentable weight. As such, claim 52 is anticipated for the same reasons as is claim 1, from which it depends.
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, 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.
Claims 20-21 and 24-26 are obvious over Hamed:
Claims 20-21 and 24-26 are rejected under 35 U.S.C. § 103 as being unpatentable over Hamed.
With respect to claims 20 and 21, Hamed does not expressly distinguish study subjects according to whether their infections are of methicillin-susceptible or methicillin resistant S. aureus. Hamed does, however, expressly teach that ceftobiprole is active against both methicillin-susceptible and methicillin resistant S. aureus. As such, it would have been obvious to perform the method of Hamed on patients having blood infected with methicillin-susceptible S. aureus and to perform the method on patients having blood infected with methicillin resistant S. aureus.
Claims 24-26, depending from claim 23, specify the different antibiotic with which the patient has received previous treatment. As noted with respect to claim 23, Hamed teaches that some patients have received previous treatment with an antibiotic, but Hamed does not specify the antibiotic(s). Hamed does, however, teach that vancomycin, daptomycin, and beta-lactam antibiotics are standard-of-care for SAB (pg. 36, Rationale for investigating ceftobiprole in SAB, including IE). It thus would have been obvious to apply the method of Hamed to patients having previous treatment with an antibiotic, specifically when the previous antibiotic was vancomycin, daptomycin, or a β-lactam.
Claims 32-33 are obvious over Hamed and Zhanel:
Claims 32-33 are rejected under 35 U.S.C. § 103 as being unpatentable over Hamed, in view of the non-patent publication, Pharmacodynamic activity of ceftobiprole compared with vancomycin versus methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate Staphylococcus aureus (VISA) and vancomycin-resistant Staphylococcus aureus (VRSA) using an in vitro model, J. Antimicrob. Chemother., 64, pgs. 364-369 (2009) by Zhanel et al. (hereinafter, “Zhanel”).
Claims 32 and 33 recite the method of claim 1 wherein the S. aureus has a vancomycin MIC of higher than 2 mg/L or higher than 4 mg/L. Hamed is applied to claims 32-33 as to claim 1, but does not expressly teach this feature. It would have been obvious to apply the method of Hamed to patients having an S. aureus blood infection by a strain that is somewhat vancomycin resistant, however, because ceftobiprole was well-known in the art to be effective against strains of S. aureus having appreciable vancomycin resistance. See, for example, Zhanel.
Zhanel teaches a study of bacteriostatic and bactericidal activity of ceftobiprole and vancomycin against various strains of S. aureus, including vancomycin-intermediate S. aureus (VISA) and vancomycin-resistant S. aureus (VRSA) – Abstract; Background. Zhanel teaches that VISA has vancomycin MIC of 2-4 mg/L while VRSA has vancomycin MIC of 64 mg/L (i.e. minimal effect); but that ceftobiprole is effective against both types, with MICs [Symbol font/0xA3]2 mg/L and bactericidal effect with ≥3 log10 killing (Abstract; Results). Given the notable effectiveness of ceftobiprole against strains of S. aureus having vancomycin MIC greater than 2 or 4 mg/L, it would have been obvious to apply the method of Hamed against patients harboring an infection by such strains, and one would have had a reasonable expectation of success in applying the method to such patients.
Claim 36 is obvious over Hamed and Jones:
Claim 36 is rejected under 35 U.S.C. § 103 as being unpatentable over Hamed, in view of the non-patent publication, Recent advances in the rational design and optimization of antibacterial agents, MedChemComm, 7, pgs. 1694-1715 (2016) by Jones et al. (hereinafter, “Jones”).
Claim 36 recites the method of claim 1 wherein the ceftobiprole is administered as the sodium salt of ceftobiprole medocaril. Hamed is applied to claim 36 as to claim 1, but does not expressly teach that the ceftobiprole medocaril is a sodium salt. It would have been obvious, however, to use the sodium salt, as it was well-known that this is the commonly used and marketed form of ceftobiprole. See, for example, Jones.
Jones, a review, teaches that ceftobiprole was temporarily postponed for approval in the Europe and discontinued in Canada due to concerns from U.S. and European regulatory agencies, but was then modified with the medocaril solubilizing group and widely approved and marketed as ceftobiprole medocaril sodium (pg. 1696, right column, first full paragraph). It would have been obvious to use this widely marketed form in the method of Hamed.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEXANDER K SHOWALTER whose telephone number is (571)270-0610. The examiner can normally be reached M-F 9:00 am to 5:00 pm, eastern time.
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/ALEXANDER K. SHOWALTER/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
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