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 .
Prosecution Reopened
As stated in the Notice of Reopening of Prosecution Due to Consideration of an Information Disclosure Statement Filed After Mailing of a Notice of Allowance, the Notice of Allowance dated 9/15/2025 has been withdrawn. In view of the withdrawal of the Notice of Allowance, the current claims under examination are dated 7/17/2025.
Prosecution on the merits of this application is reopened on claims 1, 4-6, 12, 14, and 16-21 are under examination.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 7/17/2025 has been entered.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such claim limitation(s) is/are: “component” in claims 20-21.
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
Claim Rejections - 35 USC § 112
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.
Claims 12, 14 and 16-21 are 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 12 recites the limitation "the indicator protein complex" in line 7. There is insufficient antecedent basis for this limitation in the claim. This rejection affects claims that depend from claim 12.
For claims 20-21, the claim limitation “component” invokes 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. However, the written description fails to disclose the corresponding structure, material, or acts for performing the entire claimed function and to clearly link the structure, material, or acts to the function.
The specification does not describe the structure that can be used to perform the function of “capturing the particular bacterium of interest” (claim 20) or “isolating the particular bacterium of interest from other components in the sample” (claim 21).
Therefore, the claim is indefinite and is rejected under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph.
Applicant may:
(a) Amend the claim so that the claim limitation will no longer be interpreted as a limitation under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph;
(b) Amend the written description of the specification such that it expressly recites what structure, material, or acts perform the entire claimed function, without introducing any new matter (35 U.S.C. 132(a)); or
(c) Amend the written description of the specification such that it clearly links the structure, material, or acts disclosed therein to the function recited in the claim, without introducing any new matter (35 U.S.C. 132(a)).
If applicant is of the opinion that the written description of the specification already implicitly or inherently discloses the corresponding structure, material, or acts and clearly links them to the function so that one of ordinary skill in the art would recognize what structure, material, or acts perform the claimed function, applicant should clarify the record by either:
(a) Amending the written description of the specification such that it expressly recites the corresponding structure, material, or acts for performing the claimed function and clearly links or associates the structure, material, or acts to the claimed function, without introducing any new matter (35 U.S.C. 132(a)); or
(b) Stating on the record what the corresponding structure, material, or acts, which are implicitly or inherently set forth in the written description of the specification, perform the claimed function. For more information, see 37 CFR 1.75(d) and MPEP §§ 608.01(o) and 2181.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Derda et al. (WO 2013/059946; published May 2, 2013) and further in view of Waidmann et al. (Bioengineered Bugs, 2011, 2(1): 8-16) and England et al. (Bioconjug Chem., 2016 May 18, 27(5): 1175–1187).
The instant claims are directed to a recombinant indicator bacteriophage comprising a codon-optimized indicator gene inserted into the bacteriophage genome and a protease cut site, wherein the indicator gene encodes a peptide or polypeptide subunit of an indicator protein, and wherein the peptide or polypeptide subunit is a first subunit and is complementary to a second polypeptide subunit of the indicator protein.
Derda et al. teaches a bacteriophage comprises a reporter gene, and a coat protein from which an N-terminal portion has been removed to produce a truncated coat protein that renders the bacteriophage non-infective (see paragraph [012]). The bacteriophage comprises a modified coat protein gene that expresses a chimeric coat protein having a protease cleavage site on the N-terminal side of a polypeptide binding ligand or a chemical modification site, wherein cleavage at the protease cleavage site truncates the chimeric coat protein by removal of an N-terminal peptide (see paragraph [015]). The reporter gene can be luciferase (see paragraph [051]) [claim 4].
As stated above, Derda et al. teaches that the reporter gene can be luciferase. Specifically, Derda et al. states “it is well known that infection of bacteria by phage can be accompanied by a visible readout if phage infection delivers a specific reporter gene to bacteria, for example the β-galactosidase gene (lacZ) or the luciferase gene” (see paragraph [087]). Further, Derda et al. defines a reporter gene as “green fluorescent protein and other fluorescent proteins, luciferase and other luminescent proteins, galactosidase and other enzymes activity of which could be detected” (see paragraph [051]).
Derda et al. does not teach that the luciferase is a first subunit and is complementary to a second polypeptide subunit of the indicator protein. However, England et al. teaches that NanoLuc (NLuc), a small luciferase protein, offers several advantages, including enhanced stability, smaller size, and >150-fold increase in luminescence (see the Abstract). Regarding Nluc, England et al. states that:
“Dr. Shimomura identified the bioluminescent properties of the deep-sea shrimp Oplophorus gracilirostris in 1978. The intact luciferase contains two regions composed of a 35 kDa and 19 kDa subunit each, and, in its natural state, uses coelenterazine as a substrate. However, this enzyme has undergone extensive development, with the 19 kDa subunit being identified as the catalytic portion for bioluminescence in 2000. Since that time, this subunit has been modified and a novel substrate, furimazine, developed, to create the system known as NLuc.
Therefore, luciferase NLuc is a first 19kDa subunit that is complementary to a second 35kDa subunit of the indicator protein.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use known luciferase proteins (e.g., NLuc) in the reporter bacteriophage of Derda et al. One would have been motivated to do so and there would have been a reasonable expectation of success given the teaching of Derda et al. that luciferase in general can be used and given the teachings of England et al. that NLuc offers several advantages, including enhanced stability, smaller size, and >150-fold increase in luminescence.
Derda et al. does not teach that the reporter gene is codon-optimized. However, Waidmann et al. teaches optimizing the codon usage for lux gene in Gram-positive bacteria. The codon-optimization was performed to overcome poor expression in Gram-positive bacteria (see page 11, left column). Waidmann et al. teaches codon-optimization of luciferase genes for expression in mammalian cells (see page 13, right column).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the reporter gene of Derda et al. and use a codon-optimized version of the reporter gene (e.g., codon-optimized NLuc). One would have been motivated to do so and there would have been a reasonable expectation of success given the teachings of Waidmann et al. (codon-optimization improves expression of luciferase in a particular host cell).
Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Claims 5 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Derda et al. (WO 2013/059946; published May 2, 2013), Waidmann et al. (Bioengineered Bugs, 2011, 2(1): 8-16) and England et al. (Bioconjug Chem., 2016 May 18, 27(5): 1175–1187) as applied to claims 1 and 4 above, and further in view of Gil et al. (WO 2017/127434; published July 27, 2017).
The instant claims are directed to the recombinant phage of claim 1, where the phage further comprises an untranslated region upstream of the codon-optimized indicator gene, wherein the untranslated region includes a bacteriophage late gene promoter and a ribosomal entry site (claim 5). The instant claims are further directed to a cocktail composition comprising at least two different types of recombinant bacteriophages, wherein at least one of the recombinant bacteriophages comprises an indicator gene according to claim 1 (claim 6).
The teachings of Derda et al., Waidmann et al. and England et al. are outline above and incorporated herein. Derda et al., Waidmann et al. and England et al. do not teach the limitations of instant claims 5 and 6. However, Gil et al. teaches a recombinant bacteriophage comprising an indicator gene inserted into a late gene region of a bacteriophage genome. Gil et al. also teaches that the indicator gene, which can be codon-optimized, can be inserted into an untranslated region to avoid disruption of functional genes, leaving wild-type phage genes intact, which may lead to greater fitness when infecting non-laboratory strains of bacteria (see page 2, line 20 to page 3, line 5; page 21, lines 19-29; claims 1, 3 and 4; Figure 3 and page 15, lines 21-23).
For claim 6, Gil et al. teaches compositions that include the recombinant indicator bacteriophage. For example, compositions can include one or more wild-type or genetically modified infectious agents (e.g., bacteriophages) and one or more indicator genes. In some embodiments, compositions can include cocktails of different indicator phages that may encode and express the same or different indicator proteins (see page 3, lines 27-31 and page 19, lines 9-12).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the bacteriophage of Derda et al. and insert the codon-optimized indicator gene into an untranslated region of the bacteriophage genome. One would have been motivated to do so and there would have been a reasonable expectation of success given the teachings of Gil et al. (insertion of the indicator gene into an untranslated region to avoid disruption of functional genes, leaving wild-type phage genes intact, which may lead to greater fitness when infecting non-laboratory strains of bacteria). It would also be obvious for one of ordinary skill in the art to produce a cocktail of the indicator phages to enable detection of more than one host cell type in a sample. One would have been motivated to do so for a more efficient assay (detecting more than one host cell type at once versus detecting each host cell one at a time).
Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Nicole Kinsey White whose telephone number is (571)272-9943. The examiner can normally be reached M to Th 6:30 am to 6:00 pm.
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/NICOLE KINSEY WHITE/Primary Examiner, Art Unit 1672
Prosecution Insights