DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
2. The amendment, filed 10/02/25, has been entered. Claims 1, 3, 6, 20, and 22-30 are pending and under examination. Claims 2, 4-5, 7-19, and 21 are cancelled. Claims 22-30 are newly added.
Withdrawal of Objections/Rejections
3. The following are withdrawn from the Office Action, filed 07/02/25:
The objection to claim 11, found on page 3 at paragraph 6, is moot in light of Applicant’s cancellation thereof.
The rejection of claim 16 under 35 U.S.C. 112(b) as being indefinite, found on page 3 at paragraph 8, is moot in light of Applicant’s cancellation thereof.
The rejection of claims 1-10, 16-17, and 19-20 under 35 U.S.C. 102(a)(1) as being anticipated by Benjamin et al. 1993 (EP 0 605 003 A2), found on page 4 at paragraph 11, is withdrawn in light of Applicant’s amendments thereto; specifically, amending independent claim 1 to include limitations of dependent claim 11 which was not included in the rejection. For clarity of record, it is noted that Applicant’s assertion that “…the Examiner states that a disclosure of Vibrio as target microorganism in Benjamin should be interpreted as tantamount to a disclosure of a TAL/LAL based test” (emphasis in original, see Remarks page 8) is erroneous. There is no statement in the Office Action filed 07/02/25 that even remotely resembles this characterization and, as set forth above, the dependent claim which encompassed the limitation regarding TAL/LAL-based tests was not included in the rejection.
The rejection of claims 1-2, 4-5, 9-11, 17, and 19 under 35 U.S.C. 102(a)(1) as being anticipated by Bashar et al. 2008 (An Improved in Vitro Pyrogen Test To Detect The Presence of Endotoxin Containing Bacteria Using Limulus Amoebocyte Lysate Assay From Pharmaceutical Raw Product; S. J. Pharm. Sci. 1(1&2): 76-79) found on page 6 at paragraph 12, is withdrawn in light of Applicant’s amendments thereto; specifically, amending independent claim 1 to include limitations of dependent claim 7 which was not included in the rejection.
New Rejections Necessitated by Applicant’s Amendments
New Rejection: Claim Rejections - 35 USC § 112
4. 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.
5. Claims 1, 3, 6, 20, and 22-30 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Newly amended claim 1 and newly added claim 22 are indefinite because it is unclear what “… a carrier comprising a transfer structure with a temporary magnetic field…” encompasses. In the interest of compact prosecution, the limitation will be interpreted to encompass as little as a magnet (i.e. a carrier) that is moveable (i.e. movement would cause a temporary magnetic field in the local area); nevertheless, clarification is required to ascertain what additional structures, if any, are required.
The term “modified” in claim 24 is a relative term which renders the claim indefinite. The term “modified” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. In other words, how much modification is permitted to remain included (or to then be excluded) from the claim scope? In the interest of compact prosecution, the limitation will be interpreted to encompass all bacterial selective media because one of ordinary skill in the art could reasonably start with TSB medium and generate a selective media by adding and/or subtracting the necessary components. To negate this rejection, the required elements of the bacterial growth media should be identified and claimed. Nevertheless, clarification is required to ascertain what is in the enrichment medium used.
Claims 25, 26, 28 and 29 each recites the limitation "the incubation step" in line 1. There is insufficient antecedent basis for this limitation in the claim because there is no incubation step positively recited in claim 22 from which each depends. In the interest of compact prosecution, the limitation will be interpreted to encompass any incubation step; nevertheless, clarification is required to ascertain the metes and bounds of these claims.
Claim 27 depends from claim 2, which has been cancelled. Thus, it is unclear where/how to integrate the incubation step and clarification is required.
Thus, clarification is required to remove ambiguity of scope from these claims.
New Rejection: Claim Rejections - 35 USC § 102
6. 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.
7. 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.
8. Claims 1, 20, 22, and 24-30 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Payne et al. 1993 (Separation of bacteria using agglutinins isolated from invertebrates; Journal of Applied Bacteriology 74: 276-283).
Payne teaches that the art (circa 1980s) recognized that the efficacy of many rapid methods for the microbiological examination of foods would be improved if the target organisms could first be separated from a sample and then concentrated prior to analysis (e.g. see page 276, introduction). Payne teaches methods for detecting Gram negative bacteria in food samples comprising steps wherein steak or raw egg (i.e. a sample) was inoculated with 1 ml of overnight bacterial culture, including Salmonella and/or E. coli (i.e. a Gram-negative target microorganism already present in the sample), prior to the addition of 90 ml of quarter strength Ringer's solution (i.e. combining the sample with a viability preserving medium selected for the target organism to keep the microorganism viable), and then added to 130 µI of hemolymph liganded Dynabeads® (i.e. providing separation material upon magnetic beads) in 20 ml plastic-stoppered glass vials (i.e. undertaking a selection process wherein the selection process comprises a separation material that is specific to a cell wall saccharide, for example, LPS for magnetic separation) and incubated at 4° C for 3 h (i.e. incubation is at least 15 minutes; incubation between 2 and 8 hours; total time less than 10 hours) on an automatic tube roller; and then the beads were concentrated with the magnetic particle concentrator (i.e. using a carrier comprising a transfer structure with a temporary magnetic field to remove the magnetic beads) and the number of bacteria adsorbed to the beads were assessed by spread-plate colony counts (i.e. encompasses log phase growth on enriched agar-media); and then washed twice in 1 ml of quarter strength Ringer's solution (i.e. requires transfer to another solution; also a washing step before the testing step); and then incubated at 4° C for a further 30 min (i.e. total time still under 10 hours) with a cocktail of possible competing substrates containing fetuin, N-acetyl galactosamine, N-acetyl glucosamine, glucose and mannose (i.e. also comprises use of another solution); and then bacteria released were again assessed by plate counts (i.e. meeting broadest reasonable interpretation of testing the transferred, selected material using a LAL “based” assay because the released bacteria are released from a bead conjugated to a Limulus amebocyte lysate protein; see page 277, Materials and Methods; Tables 1 and 3; and page 279, Results; meeting limitations found in instant claims 1, 20, 22, 25, 26, and 30). Payne teaches the use of selective enrichment media for particular targeted bacteria (e.g. page 277; each of which meets the broadest reasonable interpretation of claim 24; i.e., a “modified” TSB, since each one can be generated from TSB by selective modifications to make YOB, NB and/or CB). Payne teaches that overnight broth cultures of the targeted bacteria were grown in the corresponding selective media at 37°C (page 277, left column; meeting broadest reasonable interpretation of an incubation step in dependent claims 27, 28 and 29).
Therefore, Payne anticipates the invention as claimed.
New Rejection: Claim Rejections - 35 USC § 103
9. 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.
10. 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.
11. 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.
12. Claims 1, 6, 22-25, and 27-29 are rejected under 35 U.S.C. 103 as being unpatentable over Bashar et al. 2008 (S. J. Pharm. Sci. 1(1&2): 76-79) in view of Kang et al. 2016 (WO 2016/077067A2) and Payne et al. 1993 (Separation of bacteria using agglutinins isolated from invertebrates; Journal of Applied Bacteriology 74: 276-283).
Bashar teaches sampling methods for detecting the LPS of Gram-negative bacteria, including E. coli, comprising processing ten grams of raw material transferred to a sterile beaker containing ninety (90) ml sterile distilled water to make 10-1 dilution; followed by 1 ml of the sample being transferred to an enrichment broth and incubated at 37° C and then later streaked on petri dishes containing selective agar media while another 1 ml from enrichment broth being loaded into blank petri dishes and then selective media poured and incubated at 37° C for 18 hours and then analyzed using the conventional and microplate LAL methods for endotoxin (e.g. see page 77; meeting limitations found in instant claims 1, 22, 23, 25, 27, 28 and 29). Bashar teaches Eosin Methylene Blue (EMB) agar was used to selectively target E. coli (e.g. see page ; meeting broadest reasonable interpretation of the selective media of claim 24).
The difference between the prior art and the invention is wherein the separation material comprises a suitable antibody material is provided upon magnetic beads for magnetic separation (e.g. see newly amended claim 1 and newly added claim 22) and wherein results are produced in less than 10 hours (i.e. the prior art method appears to take at least 18 hours).
However, Kang teaches similar methods of detecting a target, including both Gram negative bacteria (e.g. E. coli) and endotoxins thereof (i.e. LPS), wherein the use of magnetic particles (i.e. beads) conjugated to target-binding molecules, including antibodies, including Limulus anti-LPS factor, is taught as advantageous for capturing, separating, and removing a target molecule from a fluid sample because adding target-binding magnetic particles to already developed detection methods, including ELISA-type assays in microtiter well plates significantly improved capture efficiency of the target (e.g. [0002, 0008-11, 0024-0025, 0029, 0040, 0043, 0047, 0074, 0093, 0102-0105, 0110-0116, 0136]; Figure 6; and Example 4).
In addition, Payne teaches that the art (circa 1980s) recognized that the efficacy of many rapid methods for the microbiological examination of samples would be improved if the target organisms could first be separated from a sample and then concentrated prior to analysis (e.g. see page 276, introduction).
Therefore, it would have been prima facie obvious, before the effective filing date of the claimed invention, to a person of ordinary skill in the art, to modify methods for detecting LPS (i.e. endotoxin) of Gram-negative bacteria, including E. coli, as taught by Bashar, by using target-binding magnetic particles, thereby arriving at the claimed invention, to significantly improve the efficiency of Bashar’s detection methods, as taught by Kang. In addition, the improved efficiency would reasonably be expected to reduce the overall time for the assay to produce results (i.e. “time” would be recognized by a skilled artisan as a results-effective variable; see also MPEP 2144(II)). Therefore, the combination has a beneficial result; however, the combination amounts to no more than a predictable use of prior art elements according to their established functions.
The person of ordinary skill in the art would have been motivated to make the modification because the art had long (i.e. over 40 years) recognized that the efficacy of a method for the microbiological examination of samples would be improved if the target organisms could first be separated from a sample and then concentrated prior to analysis, as taught by Payne. Further, the ‘improvement’ is technology-independent (i.e. improved efficiency) since the combination results in a process that is more desirable, for example, because it is stronger, cheaper, cleaner, faster, lighter, smaller, more durable, or more efficient and MPEP 2144(II) states that since the desire to enhance commercial opportunities by improving a process is universal, and even common-sensical, there exists in these situations a motivation to combine prior art references.
The person of ordinary skill in the art would have had at least a reasonable expectation of success because Bashar had already taught a method for detecting Gram negative bacteria (e.g. E. coli) and the endotoxins (i.e. LPS) thereof, comprising use of LAL-based assays in an ELISA type format (e.g. sandwich assay in microplate wells); and Payne had already taught microbiological examination of samples would be improved if the target organisms could first be separated from a sample and then concentrated prior to analysis; and Kang had already demonstrated that adding antibody-bound magnetic beads (i.e. target-binding magnetic particles) to similar methods of detection for E. coli significantly improved the assay’s efficiency as compared to the same assay without the target-binding magnetic particles. Therefore, the combination leads to expected results because each element performs the same function as it does individually.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that the use of known techniques to improve similar devices, methods or products in the same way is obvious because enhancing a particular class of devices, methods, or products has been made part of the ordinary capabilities of one skilled in the art based upon the teaching of such improvement in other situations. In the instant case, Bashar teaches a “base” method for detection of endotoxin and/or particular Gram negative bacteria (e.g. E. coli) comprising selective enrichment and LAL-based detection assays, and Kang teaches a comparable method for detecting endotoxin and/or particular Gram negative bacteria (e.g. E. coli) wherein the use of antibody-bound magnetic particles (i.e. target-binding magnetic particles) is taught as advantageous. Thus, one of ordinary skill in the art could have applied the known technique of Kang to the base method taught by Bashar and yield predictable results (i.e. the same advantages).
Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
New Rejection: Claim Rejections - 35 USC § 103
13. Claims 1, 3, 6, 20, and 22-30 are rejected under 35 U.S.C. 103 as being unpatentable over Benjamin et al. 1993 (EP 0 605 003 A2), in view of Pepe et al. 2010 (US 2010/0041061).
Benjamin teaches methods for detecting the presence of an organism comprising a) combining a sample to be tested for the presence of a selected organism with a magnetic solid support having immobilized thereon antibodies to said selected organism, to thereby capture cells of said selected organism from said sample; b) exposing to a magnetic field said magnetic beads having bound thereto said first antibodies and captured selected organisms to thereby separate said magnetic solid support from said sample; c) culturing the captured magnetic solid support and captured selected organisms on a solid medium to form colonies of said selected organism; d) contacting said colonies with a colony lift membrane whereby some colony material adheres to said membrane (i.e. is separated); and e) treating said membrane to detect the presence on said membrane of material from said colonies of said selected organism (see abstract and Benjamin claim 1; meeting limitations found in instant claims 1, 6, and 23). Benjamin teaches the organism is bacteria, yeast, or mold, including Escherichia, Salmonella, and/or Vibrio (i.e. Gram-negative bacteria having, by definition, LPS, aka endotoxin; see Benjamin claims 10-11). Benjamin teaches the captured and immobilized bacterial cells are spread on a medium on which the cells will grow and are incubated for a time sufficient to form bacterial colonies visible to the eye (i.e. encompasses log phase growth), and that particular media for incubation depends upon the bacteria of interest to be detected, but that such media are per se known to those skilled in the art for various bacteria, as are the incubation times and conditions (i.e. teaches one of ordinary skill in the art would recognize incubation times and temperatures as results-effective variables; see MPEP 2144.05), depending upon the particular bacteria of interest, with sufficient growth may be accomplished in as little as 6 hours or less (i.e. less than 10 hours; see column 9, step 3; meeting limitations found in newly amended claim 1 and newly added claim 22). Benjamin teaches combining the sample with PBS (see column 14, Example 1; meeting limitations found in instant claim 3). Benjamin provides examples for detecting target bacteria via antibodies attached to magnetic beads comprising combining samples with PBS, centrifuging, washing, and plating the separated magnetic beads on the surface of a petri dish containing selective media selected to correspond to maintaining the target of interest (i.e. viability-preserving enrichment media for promoting selective growth of bacteria) at 37°C (see Example 1; meeting limitations found in instant claims 1, 3, 6, 20, 22, 24, 25, 26, 27, 28, 29, and 30 with sufficient specificity). Benjamin teaches the assay is particularly preferred for detecting pathogenic, Gram negative bacteria, including Escherichia coli (e.g. see column 4).
Therefore, the difference between the prior art and the invention is an additional step of testing the selected (i.e. captured) material with an LAL or TAL based detection method, found in newly amended claim 1 and newly added claim 22.
However, Pepe teach similar methods of detection of Gram negative bacteria, including E. coli, and/or the endotoxins (i.e. lipopolysaccharides) thereof, comprising contacting a sample an inactive acidic protease and an amebocyte lysate selected from the group consisting of lysates from Limulus and Tachypleus (i.e. an LAL or TAL based detection method; see [0012-15, 0022-26, 0029]; and Example 1). Pepe teaches the method improves sensitivity of detection methods (e.g. see Example 2). Pepe teaches endotoxin is also known as lipopolysaccharide (LPS) and is an integral component of the Gram negative bacterial cell membrane and is responsible for many, if not all, of the toxic effects that occur during Gram-negative bacterial sepsis (e.g. [0001]).
Therefore, it would have been prima facie obvious, before the effective filing date of the claimed invention, to a person of ordinary skill in the art, to combine the methods for detecting the presence of a Gram negative bacterium, including E. coli, comprising the use of magnetic solid supports (e.g. magnetic beads and magnetic separation) having immobilized thereon antibodies specific for the targeted E. coli, as taught by Benjamin, with methods for detecting the presence of a Gram negative bacterium, including E. coli, and/or endotoxins thereof, further comprising the use of LAL and/or TAL-based detection methods, in order to improve the overall sensitivity of the detection of E. coli and/or its endotoxin, as taught by Pepe. Therefore, each and every element is taught in the prior art and the combination has a beneficial result; however, the combination amounts to no more than a predictable use of prior art elements according to their established functions and MPEP 2144.06 states that combining equivalents known for the same purpose is prima facie obvious.
The person of ordinary skill in the art would have been motivated to make the modification because endotoxin was the integral component of a Gram negative bacterial cell membrane and was recognized as responsible for many, if not all, of the toxic effects that occur during Gram-negative bacterial sepsis, as taught by Pepe.
The person of ordinary skill in the art would have had a reasonable expectation of success because Benjamin already taught methods of detection comprising the use of antibody-bound magnetic beads for the capture and separation of a particular target, including E. coli, and Pepe had already taught similar methods for detection comprising improved LAL and/or TAL based assays having improved sensitivity. Therefore, the combination leads to expected results because each element performs the same function as it does individually.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that combining prior art elements according to known methods to yield predictable results, is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results. In the instant case, all elements (i.e. methods for detecting the presence of a Gram negative bacterium, including E. coli, comprising the use of anti-bound magnetic beads and magnetic separation; and methods for detecting the presence of a Gram negative bacterium, including E. coli and/or endotoxins thereof, comprising the use of LAL and/or TAL-based detection) were known in the art. In addition, combining these elements yields a method wherein each element merely performs the same function as it does separately; thus, the results of the combination would be recognized as predictable to one of ordinary skill in the art. Therefore, it would have been obvious to a person of ordinary skill in the art to combine these prior art elements according to a known method to yield predictable results.
Accordingly, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Conclusion
14. No claims are allowed.
15. 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).
16. 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.
17. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARY MAILLE LYONS whose telephone number is (571)272-2966. The examiner can normally be reached on Monday-Friday 8 am to 5 pm EST. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http: //www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gary Nickol can be reached on (571)-272-0835. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MARY MAILLE LYONS/Examiner, Art Unit 1645
November 3, 2025