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 .
Election/Restrictions
1. The Election filed 3/30/2026, in response to the Office Action of 2/10/2026, is acknowledged and has been entered. Applicants elected without traverse Group I and the species of the protein encoded by SEQ ID NO: 144 (TACDTD2 or TROP2) disclosed in Table 10. Claims 1-6, 54-57, and 59 are pending. Claims 10-15, 53, and 58 have been withdrawn from further consideration by the examiner under 35 CFR 1.142(b) as being drawn to non-elected inventions. Claim 3 is drawn to a non-elected species but the species of citrullinated vimentin from Table 1 of claim 3 is being rejoined to the examined claims.
Thus, claims 1-6, 54-57, and 59 are currently under prosecution as drawn to the elected and rejoined species of protein encoded by SEQ ID NO: 144 and citrullinated vimentin.
Priority
2. Application claims the benefit and priority of PCT/US2022/071434 filed on 3/30/2022, which claims the benefit and priority of provisional application 63/168,164 filed on 3/30/2021. Upon review of the provisional application, the present subject matter is disclosed in the provisional application. Therefore priority for the present application is granted to the 63/168,164 and the effective filing date of 3/30/2021.
Claim Objections
3. Claims 1 and 6 are objected to because of the following informalities: The claims refer to proteins encoded by genes listed in “Table 1, 2, and 10”, however, the claims should recite the relevant material from Table 1, 2, and 10 in the claims for clarity. MPEP 2173.05(s) states: “Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table “is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience.” Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted). Reference characters corresponding to elements recited in the detailed description and the drawings may be used in conjunction with the recitation of the same element or group of elements in the claims. See MPEP § 608.01(m).” Given the concise information for SEQ ID NOs in Tables 1, 2, and 10, it appears there is a practical way to define the information in Tables 1, 2, and 10 in the absence of reference to the table. Appropriate correction is required.
4. Claims 56 and 59 are objected to because of the following informalities:
Claim 56: “radioimmunoassay” is recited twice, please remove one from the list;
Claim 59: “wherein the wherein” please remove “the wherein”
Appropriate correction is required.
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.
5. Claims 1-5, 54-57, and 59 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 1 recites the phrase “classifying the patient as suffering from the cancer in response to the detected amount of the detectable label bound to the bound autoantibodies being equal to or greater than a threshold; and classifying the patient as not suffering from the cancer in response to the detected amount of the detectable label bound to the bound autoantibodies being less than the threshold.” The threshold is not defined in the claim, therefore one cannot determine what amount of detectable label bound to the bound autoantibodies is equal to, less than, or greater than the “threshold”. Therefore, one cannot determine the scope of patients classified as suffering from cancer or not suffering from cancer.
Further, with regard to claim 57, given one cannot determine which patients are classified as not suffering from cancer, one cannot determine the scope of patients further requiring testing for at least one other medical condition.
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.
6. Claims 1-6, 54-57, and 59 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature/ a natural phenomenon) without significantly more.
The claims recite a method, comprising:
providing a biological sample from a patient suffering from a cancer or suspected of suffering from the cancer;
incubating the biological sample with at least one citrullinated protein selected from the group consisting of the proteins encoded by genes listed in Table 1, the proteins encoded by genes listed in Table 2, and the proteins encoded by genes listed in Table 10, under conditions sufficient for any autoantibodies against the citrullinated protein(s) that may be present in the biological sample to bind to the citrullinated protein(s);
incubating the citrullinated protein(s) and any autoantibodies bound thereto with a detectable label under conditions in which the detectable label will bind to the bound autoantibodies and will substantially not bind to other molecules; detecting the detectable label bound to the bound autoantibodies;
classifying the patient as suffering from the cancer in response to the detected amount of the detectable label bound to the bound autoantibodies being equal to or greater than a threshold; and
classifying the patient as not suffering from the cancer in response to the detected amount of the detectable label bound to the bound autoantibodies being less than the threshold.
Further, claim 57 is drawn to the method of claim further comprising testing the patient for at least one other medical condition, in response to classifying the patient as not suffering from the cancer.
The claimed method has two possible outcomes: (1) identifying the patient suffering from cancer; and (2) identifying the patient as not suffering from cancer. Thus, the claims are directed to the judicial exception of naturally occurring levels of autoantibodies to citrullinated proteins in a biological sample of a patient as correlated to the presence or absence of cancer. This judicial exception is not integrated into a practical application because the claims recite only the detection or observation of a naturally occurring phenomenon/law of nature, which is data gathering to observe the naturally occurring phenomenon/law of nature without applying the data to a practical application.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims recite use of routine laboratory procedures to detect and observe naturally occurring levels autoantibodies and medical conditions. The claimed steps of detecting autoantibodies against citrullinated proteins and testing for associated medical conditions are considered known, routine steps and are typically taken by those in the field to perform testing of a sample and are not elements that are sufficient to amount to significantly more than the judicial exception (see MPEP 2106.05(d)). For example, Al-Jarallah et. al. (Inflammatory Bowel Diseases, 2012, 18(9): 1655-1662), Alessandri, et al. (Immunol Res., 2017, 65:524-531), Bang et al., (Arthritis & Rheumatism, 2007, 56(8):2503-2511), Van Steendam et al., (Arthtritis Res & Therapy, 2010, 12:R132), Song et al., (Front. Oncol., 2019, 9(15)) Van Gaalen et al., (Arthritis & Rheumatism, 2004, 50(3):709-715), all teach and demonstrate routine methods of detecting a detectable bound label to a bound autoantibody, including ELISA, SDS-PAGE, Western Blot, and mass spectrometry, as associated with medical conditions. Routine data gathering in order to observe a natural phenomenon/natural principle does not add a meaningful limitation to the method as it would be routinely used by those of ordinary skill in the art in order to observe the natural phenomenon/natural principle, and it fails to narrow the scope of the claims such that others are not foreclosed from using the law of nature/natural phenomenon. Methods of detecting natural phenomenon preempt all practical uses of it as others must use/detect the natural phenomenon to apply it to any other correlations, diagnosis, prognosis, therapeutic response, monitoring, etc.
To obviate the rejection, there must be at least one additional element or physical step that applies, relies on, or uses the natural principle so that the claim amounts to significantly more than the judicial exception itself. The claimed method currently fails to provide a practical application of the judicial exception and fails to add any elements that amount to significantly more than the judicial exception.
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.
7. Claim 6 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Song et al. (Frontiers in Oncology, 2019, 9(15)).
Song discloses a method of clinical detection of anti-cyclic citrulline antibodies using a kit comprising a substrate, phenylglyoxal (PG), to covalently bond citrullinated residues specifically, and used for specific probes of labeling citrullinated proteins. (See Song, pgs. 3-4). Song also discloses that a citrullinated residue that could be used would be vimentin. (See Song, pg. 1, paragraph 2).
Regarding the instructions for performing the method, it is noted that textural instructions are viewed as a recitation of intended use and therefore do not differentiate the claims from the prior art (see MPEP 2112.01). Claim 6 reads on the instructions for providing a biological sample from a patient suffering from a cancer or suspected of suffering from the cancer; incubate the biological sample with the citrullinated protein(s) under conditions sufficient for any autoantibodies against the citrullinated protein(s) that may be present in the biological sample, to bind to the citrullinated protein(s); incubate the citrullinated protein(s) and any bound autoantibodies against it/them with a detectable label, under conditions wherein the detectable label will bind to the bound autoantibodies and will substantially not bind to other molecules; detect the label bound to the bound autoantibodies; classify the patient as suffering from the cancer, in response to the detected amount of the label bound to the bound autoantibodies being equal to or greater than a threshold; and classify the patient as not suffering from the cancer, in response to the detected amount of the label bound to the bound autoantibodies being less than the threshold.
Claim Rejections - 35 USC § 103
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.
8. Claims 1-4, 54-57, and 59 are rejected under 35 U.S.C. 103 as being unpatentable over Song et al. (Frontiers in Oncology, 2019, 9(15)) and in further view of Marotta (US10132806, pub. 9/11/2014).
Song discloses the presence of citrullinated proteins, including citrullinated vimentin, can be used for the classifying a person as suffering from cancer or not suffering from cancer. (See Song, abstract; also pg. 1, paragraph 2). Song also discloses the classification method can comprise incubating a sample with at least one citrullinated protein, including vimentin from Table 1 of claim 1, under conditions sufficient for any autoantibodies against the citrullinated protein that may be present in the sample to bind to the citrullinated protein, incubate the citrullinated protein and any autoantibodies bound thereto with a detectable labelling citrullinated proteins under conditions in which the detectable label will bind to the bound autoantibodies and will substantially not bind to other molecules; and detecting the labels bound to the bound autoantibodies through an ELISA method. (See Song, pgs. 3-4 Detection and Biological Significance of Citrullination Modification).
Song also discloses the cancer being classified as a gastric cancer. (See Song, pg. 1 Introduction). Song also discloses that citrullinated proteins can be used to diagnose autoimmune disorders such as rheumatoid arthritis (RA).
Song does not disclose the samples as being a biological sample comprising blood, a blood fraction, a blood product, sputum, saliva, stool, urine, lymph fluid, prostatic fluid, gastric fluid, intestinal fluid, renal fluid, lung fluid, cerebrospinal fluid, or a tissue biopsy, where the blood product is one of serum, plasma, platelets, red blood cells, peripheral blood mononuclear cells. Song also does not disclose the detectable label as is attached to an antibody against the autoantibody and that the detectable label is a fluorescent label, an enzymatic label, a radioactive label, a luminescent label, or an affinity tag.
Marotta discloses a method comprising providing a biological sample from a subject with a certain condition and incubating the sample with at least one citrullinated proteins under conditions sufficient for any autoantibodies against the citrullinated protein that may be present in the biological sample to bind to the citrullinated protein. (See Marotta, pg. 2, column 3, paragraph 1). Marotta further discloses the biological samples include blood, a blood fraction- including plasma and serum, body fluids and tissue samples. (See Marotta, pg. 3, column 6, lines 21-29). Marotta also discloses the discloses the detectable label is attached to an antibody against the autoantibody, with the detection methods which use detection labels directed to fluorescent, enzymatic, radioactive, and affinity. (See Marotta, pg. 3, column 5 line 62- column 6, line 4).
It would have been prima facie obvious for a person of ordinary skill in the art prior to the effective filing date to combine the method of Song with the method disclosure of Marotta to produce the method as claimed in the present invention. It would have been obvious because the method of Marotta was used for identifying citrullinated proteins, similar to Song, for diagnostic purposes, as used in the claimed invention. Further, Song identifies a clinical marker for the use of cancer that has been successfully used for another diagnostic purpose in Marotta. Therefore, it would have been obvious for a person of ordinary skill in the art prior to the effective filing date to apply the method disclosed in Marotta to the method of Song with a reasonable expectation of success at classifying patients as suffering from cancer or not suffering from cancer as disclosed in the present claimed invention.
9. Claim 5 and is rejected under 35 U.S.C. 103 as being unpatentable over Song et al. (Frontiers in Oncology, 2019, 9(15)) and in further view of Marotta (US10132806, pub. 9/11/2014) as applied to claims 1-4, 54-57, and 59 above, and further in view of Young (WO 2007/095748 A1).
The limitations of claim 1 are disclosed as discussed above.
Song and Marotta do not disclose the method further comprising administering, to the patient that is classified as suffering from the cancer, a cancer treatment selected from the group consisting of surgical resection, chemotherapy, monoclonal antibody therapy, checkpoint inhibitor therapy, oncolytic virus therapy, thermal therapy, radiotherapy, a cancer vaccine comprising the citrullinated protein(s), a targeted therapy against the citrullinated protein(s), and two or more thereof.
Young teaches treating cancer using monoclonal antibodies and chemotherapy as a combination treatment. (See Young, pg. 84 lines 13-20).
It would have been prima facie obvious for a person of ordinary skill prior to the effective filing date to combine the methodology of Song and Marotta with the teachings of Young for the present claimed invention. It would have been obvious because following a diagnosis it is known in the art to apply any known treatments for the disorder. Therefore, it would have been obvious to a person of ordinary skill in the art prior to the effective filing date to apply the teachings of Young to the method of Song and Marotta with a reasonable expectation of success at treating the diagnosed cancer as claimed in the present invention.
Conclusion
10. Claims 1-6, 54-57, and 59 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LINDSAY DUNN whose telephone number is (571)272-5825. The examiner can normally be reached Monday-Friday 8-4:30.
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/LINDSAY DUNN/Examiner, Art Unit 1644 /Laura B Goddard/Primary Examiner, Art Unit 1642
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