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 .
Claims 1-11 are currently pending. Claim 1 is independent.
Priority
The Instant application claims priority as follows:
PNG
media_image1.png
34
332
media_image1.png
Greyscale
PNG
media_image2.png
20
370
media_image2.png
Greyscale
Species Election requirement
Applicant’s election, without traverse, of the
PNG
media_image3.png
298
632
media_image3.png
Greyscale
, in the reply filed on November 21, 2025 is acknowledged. Applicants state that claims 1-9 read on the elected species.
Claims 10-11 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on November 21, 2025.
Examination
Examination will begin with the elected species. In accordance with MPEP 803.02, the Markush claim will be examined fully with respect to the elected species and further to the extent necessary to determine patentability. Note that where a claim reads on multiple species, only one species needs to be taught or suggested by the prior art in order for the claim to be anticipated or rendered obvious. If on examination the elected species is found to be anticipated or rendered obvious by prior art, the Markush claim and claims to the elected species will be rejected, and claims to the nonelected species will be held withdrawn from further consideration. Should applicant, in response to a rejection of a Markush claim, overcome the rejection by amending the Markush claim to exclude the species anticipated or rendered obvious by the prior art, the amended Markush claim will be examined again. The examination will be extended to the extent necessary to determine patentability of the Markush claim. It should be noted that the prior art search will not be extended unnecessarily to cover all non-elected species.
Pursuant to MPEP 803.02, the elected patentably indistinct group of species wherein R1 is the group myo-inositol phosphoryl was searched and found unpatentable over the art as detailed below. Therefore, examination was stopped and art has been applied against the claims. During the search, sdditional prior art was found that is very relevant to the instant invention which, for the purpose of a compact prosecution, is presented in this Office Action.
Subject matter outside of the examined scope are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on November 21, 2025.
Specification Objection - Title
Applicant is reminded of the proper content of the title of the invention.
The title of the invention should be brief, but technically accurate and descriptive. See 37 CFR 1.72(a) and MPEP § 606. The title of the invention should be more descriptive of what is claimed.
Specification Objection - Abstract
Applicant is reminded of the proper content of an abstract of the disclosure.
With regard particularly to chemical patents, for compounds or compositions, the general nature of the compound or composition should be given as well as the use thereof, e.g., The compounds are of the class of alkyl benzene sulfonyl ureas, useful as oral anti-diabetics. Exemplification of a species could be illustrative of members of the class. For processes, the reactions, reagents and process conditions should be stated, generally illustrated by a single example, unless variations are necessary. See MPEP § 608.01(b), Section B.
The abstract of the disclosure is objected to because it fails to exemplify any members or formulae illustrative of its class. Correction is required. See MPEP § 608.01(b).
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.
Claim(s) 1-3, 5-7 and 9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Green et al. (ACS Cent. Sci. 2017, 3, 349-358).
Green discloses improved chemiluminescent adamantylidene 1,2-dioxetanes of formula
PNG
media_image4.png
274
580
media_image4.png
Greyscale
,
PNG
media_image5.png
98
184
media_image5.png
Greyscale
,
PNG
media_image6.png
114
294
media_image6.png
Greyscale
and
PNG
media_image7.png
82
182
media_image7.png
Greyscale
for the detection of analytes or enzymes of interest, such as β-galactosidase, alkaline phosphatase, hydrogen peroxide and GSH; wherein the improvement lies on the presence of acrylic acid, acrylate and acrylonitrile electron-withdrawing substituents at the ortho position of the phenolic oxygen. Green found a striking enhancement on the chemiluminescence emission/ efficiency with this substitution. See whole document, particularly the conclusion.
Thus, Green teaches a method comprising providing a medium comprising analytes or enzymes of interest, specifically, β-galactosidase, alkaline phosphatase, hydrogen peroxide and GSH; adding the improved targeted-chemiluminescent adamantylidene dioxetane compounds of formula 2 through 9; and detecting the emitted light.
While the preamble of the claims recites “a method for the detection of a target microorganism”, the claimed process does not require that a microorganism is present in the medium as the presence or absence (no emitted light) can be detected, and also as the claim recites “or one or more target analytes or target metabolites”. In the instant case, Green teaches a target analyte or a target metabolite and performs the same exact steps of the claimed process. Thus, Green is able to detect the presence or absence of a target microorganism by providing a medium comprising a target analyte or a target metabolite. The process of claims 5-7 and 9 does not require that the medium contains a microorganism. Since the microorganism is absent, the prior art reads on claims 5-7 and 9.
Claim Rejections - 35 USC § 103
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, 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.
Claims 1-9 are rejected under pre-AIA 35 U.S.C. 103(a) as been unpatentable over Margret Ryan et al. (Analytical Biochemistry 214, 548-556 (1993)) in view of Green et al. (ACS Cent. Sci. 2017, 3, 349-358) and Rankin et al. (J. Dairy Sci. (2010) 93:5538-5551).
Chemiluminescent adamantylidene dioxetanes, their use in detection and their mechanism were well-known in the art. See the cited references and references contained therein.
Teachings of Green et al.
Green discloses improved chemiluminescent adamantylidene 1,2-dioxetanes of formula
PNG
media_image4.png
274
580
media_image4.png
Greyscale
,
PNG
media_image5.png
98
184
media_image5.png
Greyscale
,
PNG
media_image6.png
114
294
media_image6.png
Greyscale
and
PNG
media_image7.png
82
182
media_image7.png
Greyscale
for the detection of analytes or enzymes of interest, such as β-galactosidase, alkaline phosphatase, hydrogen peroxide and GSH; wherein the improvement lies on the presence of acrylic acid, acrylate and acrylonitrile electron-withdrawing substituents at the ortho position of the phenolic oxygen. Green found a striking enhancement on the chemiluminescence emission/ efficiency with this substitution. See whole document, particularly the conclusion.
Thus, Green teaches a method comprising providing a medium comprising analytes or enzymes of interest, specifically, β-galactosidase, alkaline phosphatase (AP), hydrogen peroxide and GSH; adding the improved targeted-chemiluminescent adamantylidene dioxetane compounds of formula 2 through 9; and detecting the emitted light.
Green also taught that the phenols were masked with the enzyme-responsive substrate (triggering substrate) of formula
PNG
media_image8.png
75
108
media_image8.png
Greyscale
(colored blue in the reference) for activation by β-galactosidase; and that “to avoid steric interference as a result of the ortho substituent at the enzyme cleavage site, a short self-immolative spacer was installed between the phenolic oxygen and the galactose substrate as previously described.” The short self-immolative spacer is of formula:
PNG
media_image9.png
86
58
media_image9.png
Greyscale
. See page 353.
Green further disclosed that the activation of the chemiluminescence probes is based on removal of a protecting group from the phenolic moiety. Therefore, different phenol protecting groups could be incorporated as triggering substrates for various analytes or enzymes. To demonstrate this modular feature, they synthesized three additional probes for detection of the analytes hydrogen peroxide and glutathione (GSH) and the enzyme alkaline phosphatase (AP), in which the enzyme-responsive substrate (triggering substrate) was specific to these targets. See page 354 and 355 for probes with different dedicated triggering substrates.
Teachings of Ryan et al.
Ryan teaches a method for sensitive detection of bacterial phosphatidylinositol-specific phospholipase C (PI-PLC) in bacterial cultures of B. cereus, Cytophaga sp. and E. coli MM294 (pIC), by adding the bacterial culture to the chemiluminescent probe LUMI-PI (7)
PNG
media_image10.png
190
406
media_image10.png
Greyscale
, and capturing the emitted light. See pages 551-553. The reference teaches that S. aureus, L. monocytogenes and C. novyi are also known to secrete active PI-PLC into the growth medium, and that phosphatidylinositol (myo-inositol phosphoryl)
PNG
media_image11.png
198
182
media_image11.png
Greyscale
is a triggering substrate for bacterial phosphatidylinositol-specific phospholipase C (PI-PLC). See at least page 548.
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.012)
The difference between Applicant’s method and the prior art’s method lies in the compounds used for the detection. The instant claims require the species of formula:
PNG
media_image12.png
160
518
media_image12.png
Greyscale
or
PNG
media_image13.png
182
244
media_image13.png
Greyscale
. Green did not use phosphatidylinositol (myo-inositol phosphoryl) as enzyme-responsive substrate in their probes. Ryan used phosphatidylinositol (myo-inositol phosphoryl) as enzyme-responsive substrate (triggering substrate) in their probe but did not make the enhancements to the adamantylidene-dioxetane core probes made by Green.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
The references are in the same field of endeavor, i.e. improved enzymatically cleavable chemiluminescent adamantylidene 1,2-dioxetanes. It would have been prima facie obvious to one of ordinary skill in the art wanting to perform sensitive detection of bacterial phosphatidylinositol-specific phospholipase C (PI-PLC) in bacterial cultures of B. cereus, Cytophaga sp., S. aureus, L. monocytogenes and C. novyi, to use the enhanced adamantylidene-dioxetane core probes used in probes 3 to 9 of Green with the enzyme-responsive substrate (triggering substrate) phosphatidylinositol (myo-inositol phosphoryl)
PNG
media_image11.png
198
182
media_image11.png
Greyscale
of Ryan et al. The artisan would have expected that the detection would work since Ryan et al. taught the use of adamantylidene dioxetanes with phosphatidylinositol (myo-inositol phosphoryl) as the enzyme-responsive substrate (triggering substrate) to detect said bacteria. Further, a skilled artisan would have reasonably predicted that such a substitution would afford a striking enhancement on the chemiluminescence emission/ efficiency because this is what Green teaches that the enhanced adamantylidene-dioxetane core probes achieve.
Finding of prima facie obviousness
The Supreme Court in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. See MPEP 2143.
Examples of rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Applying KSR example rationales (A), (B) and (G), the claimed process would have been prima facie obvious.
Regarding claim 8, Green teaches a method comprising providing a medium comprising alkaline phosphatase (ALP), adding the improved targeted-chemiluminescent adamantylidene dioxetane compound of formula 8; and detecting the emitted light. Green does not teach providing a dairy product medium and pasteurizing it.
Alkaline phosphatase (ALP) is the most widely used marker of the adequacy of milk pasteurization since it is inactivated at temperatures slightly higher than those required for elimination of pathogens. Chemiluminescent assays for ALP analysis are based on the ALP-mediated dephosphorylation of adamantyl 1,2-dioxetan substrates (e.g., adamantyl-1,2-dioxetane phenylphosphate). See at least Rankin et al. at page 5543.
Thus, the ordinary skilled artisan would have been motivated to use the enhanced chemiluminescent adamantylidene dioxetane compound of formula 8 of Green to test the adequacy of milk pasteurization. The desire of scientists to improve upon what is already generally known would have provided the motivation to do this.
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.
Claim 9 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 9 is confusing because at the preamble it recites: the respective target analyte, target microorganism or target metabolite are defined as shown in the following table; while the heading on the table only describes Target microorganisms.
In addition, claim 9 recites “bacterial endotoxins” under Target microorganism.
In addition, at claim 9, what is “activity microorganism” under Target microorganism?
Conclusion
Claims 1-9 are rejected. No claim is in condition for allowance.
Note to Applicants: Not every piece of prior art found in the search has been applied against the instant claims. See MPEP 904.03.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to VALERIE RODRIGUEZ-GARCIA whose telephone number is (571)270-5865. The examiner can normally be reached Monday-Friday 9:30am-5:30pm.
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, Clinton Brooks can be reached at 571-270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/VALERIE RODRIGUEZ-GARCIA/Primary Examiner, Art Unit 1621