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 .
The response and amendment filed 10-29-2025 has been entered into the record.
Status of Claims
Claims 1-22 have been canceled. Claims 23-45 are pending and under examination.
Election/Restrictions
In view of the amendment to the claims and Applicant’s response of 10-29-2025, the restriction between Groups II and III in the requirement set forth 10/1/2025 is hereby withdrawn. Claims 23-45 are pending and under examination.
Information Disclosure Statement
The information disclosure statement has been considered. An initialed copy is enclosed.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 23-45 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because the claimed invention is directed to non-statutory subject matter.
The claims are drawn to methods for diagnosing Gram-positive cases of mastitis (see claim 23 preamble). The claim performs steps for detecting LTA in milk by means of a complex formed with lipoteichoic acid (LTA) and anti-LTA antibodies for the diagnosis of mastitis. The presence of LTA in milk is correlated in the specification with a diagnosis of Gram-positive mastitis caused by S. aureus (a Gram-positive microorganism). The correlation of the presence of LTA in a milk sample with Gram-positive mastitis is a natural phenomenon which is not patentable. The method steps are data gathering steps to determine a if the natural phenomena exists.
In the instant case, the correlation of LTA with Gram-positive mastitis is not in itself patentable. The claimed processes are not patentable unless they have additional features that provide practical assurance that the diagnostic processes are genuine application of the law of nature. The art establishes that teichoic acids were long associated with mastitis and were an antigen of choice for diagnostics (see Wolde-Mariam, WO 02/075310, page 7, lines 19-26; of record). Additionally, the correlation of various antigens in milk was known to be correlatives with a S. aureus bovine mastitis diagnosis (see Fabres-Klein et al (Eur. J. Clin. Microbiol. Infec Dis 33:2095-2104, 2014) at page 2099, Table 1. Because methods for making such determinations were well known in the art, this step simply tells interested parties (farmers, manufactures) to engage in well-understood, routine, conventional activity previously engaged by those in the field. Therefore, the instantly recited steps simply tells interested persons to gather data from which they may draw an inference in light of the correlation of the detection of the captured complex. Such activity is normally not sufficient to transform an unpatentable law of nature into a patent-eligible application of that law. As such, the claims are effectively directed to a law of nature. Applicants are directed to Mayo Collaborative Services v. Prometheus Laboratories Inc. 101 USPQ2d 1961 citing Bilski v. Kappos, 95 USPQ2d 1001, Parker v. Flook, 198 USPQ 193.
The method steps could also be interpreted as an actual wet step of "measuring" by any conceivable means, even those not discovered yet. Even in view of a wet method step in the claims, the claims fail to define patentable subject matter for the following reasons because the method claims are claiming data gathering steps and a fundamental principle of a law of nature In this instance, the claims are most similar to the fact pattern in In re Grams, 888 F.2d 835 (Fed. Cir. 1989). In Grams, the claims were drawn to a process that involved performing a clinical test (i.e. detecting LTA in a milk sample) and based on the data from that test, determining if an abnormality existed means of an algorithm (i.e. the instantly claimed association a captured complex with Gram-positive mastitis). Thus, there is no transformation of any of the tested individuals or any transformation of the patient sample, rather the claims are unpatentable because the claimed process is merely a mental step or an algorithm combined with a data gathering step. As in Grams, the claims do not require that performing the clinical testing or measuring are transformative and as such the instant claims are rendered unpatentable because the object of the test(s) were merely to obtain data.
For all the foregoing reasons, the claimed invention is directed to non-statutory subject matter. This issue may be resolved by amendment the preamble of the claim to recite “A method of detecting lipoteichoic acid (LTA) in a milk sample.
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.
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.
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 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 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.
Claims 23, 25, 26, 27, 32, 38 and 39 are rejected under 35 U.S.C. 103 as being unpatentable over Takeuchi et al (US 2014/0242612, August 28, 2014 of record) in view of Nagasawa et al (Frontiers in Veterinary Science 6:504 pages 1-12 January 2020).
Takeuchi et al rapid identification of gram-positive organisms in a sample of body fluids using an immunochromatographic strip assay. Each strip has both capture and detection antibody both of which may be the same. The antibodies can be either monoclonal or polyclonal and can be derived from any common host sources. One embodiment of the device includes two monoclonal antibodies targeting lipoteichoic acid (see page 2, paragraph [0021]). The detection antibodies are desirably conjugated to colloidal gold nanoparticles and place on the test strip to result in an assay with at least one visual signal. Gold particles of approximately 40 nm but other sizes between 20 and 80 nm are feasible as well. Other possibilities include latex particles between 100-300 nm, magnetic particles and fluorescent particles. Takeuchi et al teach that the capture antibodies are immobilized in a specific detection zone, desirably as a test line about 1mm in width perpendicular to the longest dimension of the matrix. Larger pore sizes matrices improve sample flow through the system an allow for samples with whole cell organisms to be tested without the need for any sample processing steps. In one embodiment a conjugate pad is used to receive the sample. Alternative embodiments may have an additional and separate sample pad positioned at the proximal end of the strip to receive the sample and be in physical contact with the conjugate pad to allow for fluid flow through. A wicking pad is located at the distal end and is used to draw the fluid sample through the system by capillary action. In some embodiments, a running buffer reagent in liquid form is used to help facility sample flow through the test strip. It is desirably mixed with the sample prior to addition to the test strip (see paragraphs [0023-0027]). Confirmation that the appropriate amount of sample and conjugate have passed through the system is desirable and can take the form of a test line distal to the test line that forms a visible signal with a specified amount of sample and/or conjugate exposure. The zone can be either a separate antigen known to bind the conjugated antibody or a separate antigen that requires a non-specific conjugate antibody to be added to the test strip. This line is known as the control line (see paragraph [0032]). At page 4, Table 1, a desired lateral flow assay for gram positive organisms is set forth. Takeuchi et al differ by not testing milk from a cow and not specifically exemplifying anti-LTA monoclonal antibodies as the capture and conjugate reagents.
Nagasawa et al teach detection of S. aureus in quarter milk samples that was aseptically collected (see page 5, column 1, see milk sampling procedure) form dairy cows prior to milking and prior to administration of antibiotics . Nagasawa et al teach an immunochromatographic means of detection of S. aureus. Nagasawa et al teach that mastitis is associated with S. aureus infection (see page 1, abstract) and that such methods are highly sensitive S. aureus screen methods for the diagnosis of bovine mastitis.
It would have been prima facie obvious to one having ordinary skill in the art at the time of filing to detect mastitis mediated by a S. aureus infection in a dairy cow milk sample collected aseptically using the immunochromatographic test strip of Takeuchi et al where the both the capture and test antibodies are anti-LTA antibodies and monoclonal antibodies in particular and include a test strip control means according to Takeuchi et al because both Takeuchi et al and Nagasawa et al teach that the rapid detection of S. aureus in biological samples is desirable for detection of infection and monitoring for mastitis in dairy cow milk.
Claims 24, 28-31, 33-37, 42 and 43 are rejected under 35 U.S.C. 103 as being unpatentable over Takeuchi et al (US 2014/0242612, August 28, 2014 of record) and Nagasawa et al (Frontiers in Veterinary Science 6:504 pages 1-12 January 2020) as applied to claims 23, 25, 26, 27, 32, 38 and 39 above and further in view of Artursson et al (J. Dairy. Sci 93:1534-1538, 2009).
The combination of Takeuchi et al (US 2014/0242612, August 28, 2014 of record) and Nagasawa et al (Frontiers in Veterinary Science 6:504 pages 1-12 January 2020) is set forth supra. The combination differs by not teaching an enrichment step for S. aureus in milk to allow bacterial growth to a detectable level under the specific conditions set forth in claims 24, 28-31, and 37.
Artursson et al teach that a common strategy to identify S. aureus positive udder quarters to sample cows with elevated SCC, but is not uncommon that bacteria are not detected. One reason is that the concentration of bacteria in milk of an infected quarter is not static and infected quarters may show a sinusoidal shedding pattern. To increase the probability of detecting S. aureus in a single milk sample, various means of pre-enrichment have been tested (see page 1534, column 2, first full paragraph). Artursson et al teach that there was an increased probability of detecting S. aureus in milk sample with milk sample were subjected to a simple incubation step for 18 hours without additives was included before culturing (see page 1534 abstract). Artursson et al also teach an enrichment method that provides for 1 ml of fresh milk added to an equal volume of nutrient broth incubated for 4 hours at 37oC (see page 1535, column 2, see processing methods). Table 1 on page 1535 demonstrates that the enrichment method provided for similar characteristics as incubation alone. Artursson et al teach that control of mastitis and identification of infected cows is especially important to reduce spread of infections pathogens including S. aureus (see page 1534, paragraph bridging columns 1-2).
It would have been prima facie obvious to one having ordinary skill in the art at the time the invention was filed to enrich/pretreat the milk according to the standard or enrichment methods of Arturrson et al prior to contact with the with sample pad in the immunochromatographic test strip of Takeuchi et al and Nagasawa et al as combined supra because Artursson et al teach that enrichment methods may increase the probability of detecting S. aureus in a single milk sample. The mixing amounts, the incubation conditions and time period are results effective variables that are subject to optimization and therefore, any difference in volumes and time periods are prima facie obvious over the ENR conditions of Artursson et al. As to claim 37, it would have been prima facie obvious to one having ordinary skill in the art at the time to test the enriched sample prior to the next milking of the same cow so as to remove infected product and treat the cow’s mastitis/infection before it spreads and provide for adequate herd management.
Claims 40, 41, 44 and 45 are rejected under 35 U.S.C. 103 as being unpatentable over Takeuchi et al (US 2014/0242612, August 28, 2014 of record), Nagasawa et al (Frontiers in Veterinary Science 6:504 pages 1-12 January 2020) and Artursson et al (J. Dairy. Sci 93:1534-1538, 2009) as applied to claims 24, 28-31, 33-37, 42 and 43 above and further in view of Jiang et al (WO 2020/160040, August 20, 2020 with priority to January 19, 2019; of record).
The combination of Takeuchi et al (US 2014/0242612, August 28, 2014 of record), Nagasawa et al (Frontiers in Veterinary Science 6:504 pages 1-12 January 2020) and Artursson et al (J. Dairy. Sci 93:1534-1538, 2009) is set forth supra. The combination differs by not teaching a dipstick lateral flow device.
Jiang et al teach lateral flow assays can be developed to be used in a dipstick format or in a house cassette. Both dipsticks and housed tests will work in a similar way depending upon for example, industry and market requirements (page 13, lines 7-12).
It would have been prima facie obvious to one having ordinary skill in the art at the time the invention was filed to format the lateral immunochromatographic assay of Takeuchi et al (US 2014/0242612, August 28, 2014 of record), Nagasawa et al (Frontiers in Veterinary Science 6:504 pages 1-12 January 2020) as combined supra into a dipstick format for dipping in the enriched sample or incubated milk sample according to Artursson et al because Jiang et al teach that lateral flow assays can be alternately produced in a dipstick or housed format and the dipstick format would necessarily alleviate the need for a sterile device to transfer of the enriched milk or milk sample to the housed format.
Citation of Prior Art
The following art is cited to teach conventional immunoassays present in the art.
Upadhyay et al (Microchemical Journal, 137:435-442, 2018).
Zhao et al (Food Chemistry 339:127955 pages 1-8, available on line 02 September 2020).
Google English translation (CN102135540A).
Google English translation (CN102645536A).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Patricia Duffy whose telephone number is (571)272-0855. The examiner can normally be reached 8:00 am - 4 pm.
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, Daniel Kolker can be reached at 571-272-3181. 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.
/Patricia Duffy/Primary Examiner, Art Unit 1645