DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 01/28/2026 has been entered. Claims 33-35 remain under examination. Claims 16-29 and 37-39 remain withdrawn from consideration being directed to non-elected subject matter.
Claims Summary
Claim 33 is directed to a method for selecting a treatment for a subject comprising:
Obtaining a biological sample from a subject;
Detecting a MRSA microorganism or category of MRSA microorganisms in the sample using a recombinant indicator phage that has a viral late promoter; wherein the indicator phage specifically infects MRSA and is a synthetically prepared phage (claim 34), or a genetically modified naturally occurring phage (claim 35);
Selecting a treatment based on the antibiotic resistance of the specific antibiotic-resistant microorganism or category of microorganisms detected in the sample; and
Administering the treatment selected in step (iii) to the subject.
Please note that claims 34 and 35 recite product-by-process limitations with regard to how the phage is made. According to MPEP 2113, the patentability of a product does not depend on its method of production. The structure implied by the process steps should be considered, however, product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps.
The process of detecting a MRSA microorganism or category of MRSA microorganisms in the sample comprises the steps of:
Incubating the sample with at least one antibiotic to allow for enrichment of resistant bacteria for at least 5 minutes at a sufficient dose for MRSA;
Incubating the enriched samples with the recombinant indicator phage that infects the MRSA, wherein the phage comprises a codon-optimized indicator gene that results in production of a soluble indicator protein product that generates either an intrinsic signal or a soluble enzyme that generates a signal upon reaction with a substrate, upon infection; and,
Detecting the indicator protein product, wherein positive detection indicates the presence of a MRSA microorganism or category of MRSA microorganisms in the sample.
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.
Claims 33-35 remain rejected under 35 U.S.C. 103 as being unpatentable over Rey et al. (WO 2008/131230 A1, “Rey”) in view of Anderson et al. (US 2015/0218616 A1, “Anderson”) and Ventola CL (Pharmacy and Therapeutics, April 2015, 40(4):277-83, “Ventola”). The claims are summarized above and correlated with the teachings of the prior art in bold font below.
Rey discloses reporter bacteriophage whose genome has been modified to contain a reporter gene (see paragraph [0051]), which meets the limitations of an indicator phage, as well as the limitations of synthetically prepared (claim 34), and a genetically modified naturally occurring phage (claim 35). Bacteriophage that infect Staphylococcus aureus, such as P1, P14, etc., are modified to have a reporter gene that is used to detect target bacteria in patient medical samples (see paragraphs [0059] and [0061], and claims 53 and 54), and are used in a method to detect whether the target bacteria are resistant to a particular drug, such as an antibiotic (see paragraphs [0025], [0049], and [0062]). Rey’s phage comprises a detectable reporter molecule fused to a structural protein, under the control of a promoter (see paragraphs [0028], [0052] and [0074]). Examples of reporter molecules include fluorescent proteins and antibodies (see paragraph [0051] (claim 33, aspect of soluble enzyme). Although Rey does not state that the reporter molecule is codon-optimized, please note that the term “codon-optimized” in instant claim 33 does not impart any particular meaning to the indicator protein since the claim does not indicate what the codon optimization is form, nor does the claim provide any sequence to distinguish a codon-optimized indicator protein from one that is not. Thus, Rey’s reporter molecule meets the limitation of claim since the term “codon-optimized” does nothing to impart any structural difference between Rey’s reporter molecule and Applicant’s indicator protein.
Rey does not explicitly suggest a viral promoter, nor insertion of the viral promoter and reporter gene into a late gene region of the phage genome.
It would have been obvious to have selected a late viral promoter. Anderson discloses methods for rapid detection of microorganisms in clinical samples, including antibiotic-resistant bacteria (see paragraphs [0003] and [0005]). Anderson uses a genetically modified phage comprising an indicator gene in the late gene region under the control of a late viral promoter (see abstract and paragraphs [0003] and [0077]) (claim 33, viral late promoter; claims 34-35, synthetically prepared, genetically modified). Anderson teaches that the use of a late viral promoter that is derived from the original wild-type phage, for example, ensures optimal expression of the reporter (see paragraph [0077]). Also taught is that insertion of the reporter construct into the late gene region is advantageous because the late gene region includes the most abundantly expressed structural proteins, and by association, the reporter (see paragraph [0053]). Given these advantages taught by Anderson, it would have been obvious to have made Rey’s reporter phage having a late viral promoter for optimal expression, with a reasonable expectation of success.
Rey does not disclose the enrichment steps recited in the instant claims. Rey’s method does not appear to include enrichment with antibiotics prior to incubation with indicator phage. Rey’s method incubates bacteria with phage prior to contact with a drug (antibiotic, for example) (see paragraph [0062]). However, it would have been obvious to have enriched the bacteria with an antibiotic prior to exposure to the phage in order to allow the resistant bacteria to grow, thus improving sensitivity of the results. Anderson’s methods can be performed without enrichment, or with enrichment. Anderson contemplates enrichment culturing for very short times compared to traditional enrichment (see paragraph [0054]). It would have been obvious to have included a step of antibiotic enrichment of short duration, as taught by Anderson, in Rey’s method in order to improve sensitivity of the assay (see Anderson’s teachings on how the art recognizes that enrichment increases detection sensitivity, paragraphs [0004], [0005], [0031] and [0039]). Anderson does not disclose enrichment for “at least 5 minutes”. However, Anderson teaches “very short periods of time” and “much shorter period of time than traditional culturing for enrichment” (see Anderson paragraph [0054]), when traditional culturing for enrichment is, for example, about 5 hours (see Anderson paragraph [0005]). One would conclude that Anderson’s “very short periods of time” is less than about 5 hours. This meets the limitation of “at least 5 minutes”.
Rey does not specifically suggest MRSA, nor an indicator phage that specifically infects MRSA. Rey does not explicitly state that treatments are selected based on drug resistance, however, it would have been obvious to have done so. Ventola discusses antibiotic resistance for many bacteria, including MRSA, noting its resistance to certain antibiotics and susceptibility to others (see page 281, bridging paragraph of left and right columns). One would have been motivated to practice Rey’s method in the context of MRSA with phage that specifically infect MRSA, given its pathological significance, and to select a treatment for a subject having a bacterial infection based on results from Rey’s test for drug-resistant bacteria in a sample from the subject, with a reasonable expectation of success (claim 33). By culturing MRSA for enrichment, one would have been motivated to include the antibiotic against which the bacteria are resistant in order to be a favorable environment for their propagation, with a reasonable expectation of success. Therefore, the claimed invention would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Response to Arguments
Applicant’s remarks filed 01/28/2026 have been carefully considered but fail to persuade. Applicant argues that it is not obvious to use a viral late promoter in Rey’s construct because Rey uses a conditional promoter selected from any number of promoters, in contrast to the instant invention which uses a late viral promoter specifically from the original wild-type phage of the recombinant indicator phage. Applicant argues that Anderson is not directed to MRSA, and Ventola is not directed to phage, thus the two references do not cure the deficiency of Rey concerning a viral late promoter.
In response, Anderson teaches that the use of a late viral promoter that is derived from the original wild-type phage, for example, ensures optimal expression of the reporter (see paragraph [0077]). (Claim 33 does not appear to recite a limitation about the promoter being derived from the original wild-type phage. Even if it did/does, Anderson addresses that aspect.) Also taught is that insertion of the reporter construct into the late gene region is advantageous because the late gene region includes the most abundantly expressed structural proteins, and by association, the reporter (see paragraph [0053]). Given these advantages taught by Anderson, it would have been obvious to have made Rey’s reporter phage having a late viral promoter for optimal expression, with a reasonable expectation of success. As for the aspect of being MRSA-specific, this has been addressed in the rejection above.
Applicant argues that neither Rey nor Anderson disclose incubation with an antibiotic. Applicant argues that Anderson’s method does not require an enrichment step, thus one would not have been motivated to combine the teachings of Rey and Anderson. Applicant argues that Anderson’s “culturing for enrichment” (see paragraph [0054]) is for favorable propagation of microorganisms, unlike the instant method where the step of enriching antibiotic-resistant bacteria is not culturing for enrichment. Additionally, Applicant argues that none of the references teaches incubation with an antibiotic for “at least 5 minutes”.
In response, Anderson’s “culturing for enrichment” is the same as Applicant’s enrichment step in that antibiotic-resistant bacteria are propagated in a favorable media (i.e., favorable for the antibiotic-resistant bacteria, unfavorable for the non-resistant bacteria). These are the same concepts. By culturing MRSA for enrichment, one would include the antibiotic against which the bacteria are resistant in order to be a favorable environment for their propagation. The Office recognizes that Anderson’s method touts the advantage of not requiring enrichment. However, Anderson discloses that the method can be performed with enrichment for very short times compared to traditional enrichment (see paragraph [0054]). It would have been obvious to have enriched the bacteria with an antibiotic prior to exposure to the phage in order to allow the resistant bacteria to multiply, thus improving sensitivity of the results. (See Anderson’s teachings on how the art recognizes that enrichment increases detection sensitivity, paragraphs [0004], [0005], [0031] and [0039].) Thus, Anderson does not completely exclude a step of enrichment, rather, shortened enrichment compared to traditional enrichment, if desired. The aspect of “at least 5 minutes” has been addressed in the rejection above.
Applicant argues that none of the cited references use a codon-optimized indicator gene that produces a soluble protein product. This limitation has been addressed in the rejection above.
Conclusion
No claim is allowed.
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/STACY B CHEN/Primary Examiner, Art Unit 1672