DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Specification
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed. Appropriate correction is required.
Withdrawn Rejections
The rejection of claims 12-14, 17-18 and 22 under pre-AIA 35 U.S.C. 102(b) as being anticipated by Voorhees et al. (U.S. Patent Application No. 2005/0003346; cited by applicant) has been withdrawn in view of applicant’s amendments to claim 12.
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 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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 12-15, 17-18 and 22 are rejected under pre-AIA 35 U.S.C. 103 as being unpatentable over Voorhees et al. (U.S. Patent Application No. 2005/0003346; cited by applicant).
The claims are directed to a method for detecting a bacterium of interest in a sample comprising the steps of:
infecting at least one bacterium in the sample with a plurality of a parental bacteriophage, wherein the plurality of parental bacteriophage are added to the sample at a concentration of at least 6.75 x 107 PFU/mL;
lysing the at least one infected bacterium to release a progeny bacteriophage present in the bacterium; and
detecting the progeny bacteriophage, or a constituent of the progeny bacteriophage, wherein detection of the progeny bacteriophage or constituent of the progeny bacteriophage indicates that the bacterium of interest is present in the sample.
Voorhees et al. teaches a method for analyzing a test sample to detect a biomarker associated with progeny phage as a surrogate marker for target bacteria present in a sample (see paragraph [0097] and Figures 6 and 7). Regarding the sample, Voorhees et al. teaches that a raw sample containing the target bacterium is generally in a liquid form but could be a solid or a powder and may be pretreated in a variety of ways to prepare it for testing. For example, the raw sample may have been purified or filtered to remove unwanted components or to concentrate the target bacterium (claim 22). The method of Voorhees et al. involves contacting the sample with bacteriophage, which can be tagged/labeled, incubating the sample and bacteriophage mixture, lysing the bacteria with lysozyme, and detecting a progeny phage subcomponent (Figure 6) or detecting the tagged progeny phage (Figure 7) (claim 12, steps a-d). The presence of progeny phage indicates the presence of target bacteria in the sample. Voorhees et al. teaches that the parent phages are tagged in such a way that they can be separated from the progeny phage prior to the detection process (see the Abstract) (claim 13). The method can use genetically modified bacteriophage that express an indicator moiety on the capsid protein, which can be used to detect the presence of the progeny bacteriophage (see Figure 24 and paragraph [0109]) (claim 14). Voorhees et al. further teaches that bacteriophage can comprise a luciferase gene that is expressed in the bacteria upon infection and produces a light signal indicating the presence of the target bacteria (see paragraph [0011]).
Voorhees et al. does not teach that the amount of bacteriophage added is 6.75 x 107 PFU/mL. However, in the examples, Voorhees et al. teaches that MS2 phage is used to detect E. coli in a sample using the process of Figure 1 (see paragraphs [0114] and [0117] and Figure 1 below). The method of Fig. 1 shows, adding phage to a sample, incubating the mixture, lysing the bacteria containing progeny bacteriophages, and detecting the progeny bacteriophage.
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MS2 phage were added to each raw sample to give test samples with MS2 concentrations of 1 x 106 pfu/mL. The amount of phage added by Voorhees et al. was sufficient to detect E. coli in the sample.
According to section 2144.05 of the MPEP, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here 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 also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”) Here, the general conditions of the claimed method are disclosed in the prior art Voorhees et al. Thus, it is not inventive to discover optimum or other workable amounts of bacteriophage by routine experimentation. Further, applicant has not demonstrated unexpected or superior results for the claimed amount of bacteriophage added to the sample.
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.
Claim 15 is directed to the method of claim 12, wherein the progeny phage comprise an indicator moiety which is luciferase fused to the phage capsid protein.
While Voorhees et al. teaches that the bacteriophage can comprise a luciferase reporter gene or that indicator moieties can be on the bacteriophage capsid protein (see paragraph [0109] and Figure 24), Voorhees et al. does not teach that the luciferase gene can be fused to the bacteriophage capsid gene.
Given the knowledge of the skilled artisan for making fusion proteins, in particular fusion proteins comprising the bacteriophage capsid protein, it would be well within the purview of and obvious for one of ordinary skill in the art to fuse the luciferase reporter gene to the bacteriophage capsid gene. The outcome would be the same (infection of the bacteria, expression of the capsid-luciferase fusion protein, assembly of progeny phages comprising the capsid-luciferase fusion protein, and detection of progeny phage via a light signal from the luciferase. Further, applicant has not demonstrated unexpected results when the luciferase is fused to the capsid versus soluble luciferase.
Claims 17 and 18 are directed to the method of claim 12, further comprising the step of infecting indicator bacteria with the progeny bacteriophage, wherein the indicator bacteria comprise a protein that is released upon lysis of the indicator bacteria, wherein the protein can comprise a detectable moiety. Voorhees et al. teaches a phage-based detection assay where a lytic phage infection of a sample that may contain bacteria of interest. This is followed by removal of free phage from the sample, target bacteria lysis, and then infection of a second bacterium by the progeny phage where the second bacterium has a shorter doubling time than does the target bacterium (see paragraph [0010]). The second bacterium comprises a protein that will be released from the bacterium upon lysis. Voorhees et al. also teaches a method where progeny phage can be detected using a direct assay of the progeny phage or by using a genetically modified bioreporter bacterium to generate a signal indicating the presence of progeny phage in the sample. (see paragraph [0013]).
Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Response to Arguments
In the reply dated 10/27/2025, applicant argues that the 1 x 106 PFU/mL taught by Voorhees et al. is the highest concentration of parental bacteriophage for use in the disclosed method. Applicant’s arguments have been fully considered and not found persuasive.
At paragraph [0093], Voorhees et al. states: Keeping the concentration of parent phage in the test sample below the background detection limit makes for a very simple test method: add phage to the raw sample, incubate, and then detect phage biomarkers. However, there is a potential disadvantage as well. The potentially low concentration of parent phage may result in conditions where the ratio of parent phage to target bacteria in the test sample is less than 1; i.e., the Multiplicity Of Infection (MOI) is low.
One suggestion made by Voorhees et al. to overcome this potential disadvantage is to increase the incubation time. Another suggestion to overcome this potential disadvantage is to eliminate or significantly reduce the signal associated with the parent phage such that higher concentrations of parent phage can be utilized--MOIs greater than 5 (see paragraph [0093]). Thus, Voorhees et al. teaches a way to use higher concentrations of parental bacteriophage.
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.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 12-14, 17-18 and 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2 and 5 of U.S. Patent No. 9482668.
The instant claims are directed to a method for detecting a bacterium of interest in a sample comprising the steps of:
infecting at least one bacterium in the sample with a plurality of a parental bacteriophage, wherein the plurality of parental bacteriophage are added to the sample at a concentration of at least 6.75 x 107 PFU/mL;
lysing the at least one infected bacterium to release a progeny bacteriophage present in the bacterium; and
detecting the progeny bacteriophage, or a constituent of the progeny bacteriophage, wherein detection of the progeny bacteriophage or constituent of the progeny bacteriophage indicates that the bacterium of interest is present in the sample.
The patented claims are directed to a method for detecting a bacterium of interest comprising the steps of:
isolating at least one bacterium from other components in a sample;
infecting the at least one bacterium with a plurality of a lytic parental bacteriophage genetically engineered to express a soluble protein during replication,
wherein the parental bacteriophage are present in an amount to find, bind, and infect the at least one bacterium in the sample to cause a lytic infection cycle to produce 100 or more progeny phage particles in about one-half hour to one hour
incubating the at least one infected bacterium;
lysing the at least one infected bacterium to release the contents in the bacterium;
detecting the soluble protein expressed during replication of the bacteriophage,
wherein expression of the soluble protein is driven by a bacteriophage capsid promoter and the soluble protein is not a fusion protein and is not incorporated into the bacteriophage structure,
wherein detection of the soluble protein indicates that the bacterium is present in the sample, and
wherein the method detects as little as a single bacterium in the sample.
Instant claim 12 is taught by patented claims 1 and 5.
Instant claim 13 is taught by patented claims 2 and 5.
Instant claim 14 is taught by patented claims 1 and 5.
Instant claim 17 is taught by patented claim 5.
Instant claim 18 is taught by patented claim 5.
Instant claim 22 is taught by patented claims 1 and 5.
Although the claims at issue are not identical, they are not patentably distinct from each other.
The patented claims do not teach that the amount of bacteriophage added is 6.75 x 107 PFU/mL. However, the amount of phage added by the patented claims (a plurality of lytic parental bacteriophage) was sufficient to detect bacteria in the sample.
According to section 2144.05 of the MPEP, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here 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 also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”) Here, the general conditions of the claimed method are disclosed in the patented claims. Thus, it is not inventive to discover optimum or other workable amounts of bacteriophage by routine experimentation. Further, applicant has not demonstrated unexpected or superior results for the claimed amount of bacteriophage added to the sample.
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 12, 14 and 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 8 of U.S. Patent No. 12006531.
The instant claims are directed to a method for detecting a bacterium of interest in a sample comprising the steps of:
infecting at least one bacterium in the sample with a plurality of a parental bacteriophage, wherein the plurality of parental bacteriophage are added to the sample at a concentration of at least 6.75 x 107 PFU/mL;
lysing the at least one infected bacterium to release a progeny bacteriophage present in the bacterium; and
detecting the progeny bacteriophage, or a constituent of the progeny bacteriophage, wherein detection of the progeny bacteriophage or constituent of the progeny bacteriophage indicates that the bacterium of interest is present in the sample.
The patented claims are directed to a method for detecting a bacterium of interest in a sample, the method comprising the steps of:
incubating at least one bacterium with a plurality of a bacteriophage genetically engineered to have an indicator gene inserted into a late gene region of the bacteriophage, wherein the indicator gene encodes a luciferase protein such that the luciferase protein is expressed during the replication of the bacteriophage and the luciferase protein does not form a fusion protein with a native gene product, and wherein the incubating step is performed at a temperature that is at least 37 degrees Celsius and no greater than 45 degrees Celsius; and
detecting the luciferase protein,
wherein detection of the luciferase protein indicates that the bacterium is present in the sample1.
Instant claim 12 is taught by patented claim 1.
Instant claim 14 is taught by patented claim 1.
Instant claim 22 is taught by patented claim 8.
The patented claims do not teach that the amount of bacteriophage added is 6.75 x 107 PFU/mL. However, the amount of phage added by the patented claims (a plurality of lytic parental bacteriophage) was sufficient to detect bacteria in the sample.
According to section 2144.05 of the MPEP, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here 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 also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”) Here, the general conditions of the claimed method are disclosed in the patented claims. Thus, it is not inventive to discover optimum or other workable amounts of bacteriophage by routine experimentation. Further, applicant has not demonstrated unexpected or superior results for the claimed amount of bacteriophage added to the sample.
Although the claims at issue are not identical, they are not patentably distinct from each other.
Claims 12, 14 and 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3 and 9 of U.S. Patent No. 11479801.
The instant claims are directed to a method for detecting a bacterium of interest in a sample comprising the steps of:
infecting at least one bacterium in the sample with a plurality of a parental bacteriophage, wherein the plurality of parental bacteriophage are added to the sample at a concentration of at least 6.75 x 107 PFU/mL;
lysing the at least one infected bacterium to release a progeny bacteriophage present in the bacterium; and
detecting the progeny bacteriophage, or a constituent of the progeny bacteriophage, wherein detection of the progeny bacteriophage or constituent of the progeny bacteriophage indicates that the bacterium of interest is present in the sample.
The patented claims are directed to a method for detecting a microorganism in a sample, comprising:
infecting the microorganism with a lytic bacteriophage capable of infecting the microorganism to generate progeny bacteriophage and a soluble enzyme released when the microorganism is lysed by the progeny bacteriophage;
allowing the infected microorganism to be lysed by the progeny bacteriophage; and,
detecting a detectable product of a reaction catalyzed by the released soluble enzyme found in solution in the sample, wherein detection of the detectable product indicates that the microorganism is present in the sample.
Instant claim 12 is taught by patented claims 1 and 3.
Instant claim 14 is taught by patented claim 1.
Instant claim 22 is taught by patented claim 9.
The patented claims do not teach that the amount of bacteriophage added is 6.75 x 107 PFU/mL. However, the amount of phage added by the patented claims was sufficient to detect bacteria in the sample.
According to section 2144.05 of the MPEP, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here 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 also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”) Here, the general conditions of the claimed method are disclosed in the patented claims. Thus, it is not inventive to discover optimum or other workable amounts of bacteriophage by routine experimentation. Further, applicant has not demonstrated unexpected or superior results for the claimed amount of bacteriophage added to the sample.
Although the claims at issue are not identical, they are not patentably distinct from each other.
Response to Arguments
In the reply dated 10/27/2025, applicant requests that the double patenting rejections be held in abeyance. The double patenting rejections will be maintained.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 nonprovisional extension fee (37 CFR 1.17(a)) 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 Nicole Kinsey White whose telephone number is (571)272-9943. The examiner can normally be reached on M to Th 6:30 am to 6:00 pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Thomas Visone can be reached on 571-270-0684. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/NICOLE KINSEY WHITE/Primary Examiner, Art Unit 1672
1 For luciferase to be detected, the bacteria must be lysed to release the luciferase.