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 .
DETAILED ACTION
Response to Amendment
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office Action has been withdrawn pursuant to 37 CFR 1.114.
Applicants’ amendment of the claims filed 29 June 2026 has been entered. Applicants’ remarks filed 29 June 2026 are acknowledged.
Claims 1-44 are cancelled. Claims 45-64 have been added. Claims 45-64 are pending and under examination to the extent they read on the elected species: A) wherein the method comprises generating protein level data for each protein marker of a plurality of protein markers, wherein the plurality of protein markers comprises at least four markers, and wherein the at least four markers are: CRP, IL6, SAA1, and MMP3; and B-a) wherein the at least four protein markers comprise at least five markers.
Claims 45-47, 50 and 57-64 read on the elected species, and claims 48-49 and 51-56 are withdrawn as being drawn to non-elected species.
Claim Rejections Withdrawn
The rejection of claims 18, 20, 30-31, 37-39 and 41 under 35 U.S.C. 101, because the claimed invention is directed to non-statutory subject matter, is withdrawn in view that claims 18, 20, 30-31, 37-39 and 41 are cancelled.
Claim Rejections Maintained
Double Patenting
New claims 45-47, 50 and 57-64 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 11,656,227.
Applicants indicated that Applicants are prepared to file a terminal disclaimer over U.S. Patent No. 11,656,227, if appropriate in view of the allowed subject matter.
New Grounds of Objections/Rejections
Claim Objections
Claim 61 is objected to because of the following informalities:
“(predicted TJC28)0.5” should be “(predicted TJC28)0.5” or “sqrt(predicted TJC28)”;
“(predicted SJC28)0.5” should be “(predicted SJC28)0.5” or “sqrt(predicted SJC28)”; and
“log(CRPx10-6+1)” should be “log(CRPx10-6+1)”.
Appropriate correction is required.
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.
Claims 45-47, 50, 58-59 and 62-64 are rejected under 35 U.S.C. 102(a)(1), as being anticipated by Wagner et al. (US 2012/0178100 A1, Pub. Date: Jul. 12, 2012) (reference provided previously).
Wagner teaches the use of multiple biomarkers to predict the response of a patient having psoriatic arthritis (PsA) to treatment with anti-TNF therapy, in which the levels of the biomarkers are determined in a serum sample of the patient prior to initiation of anti-TNF therapy [0013] [0058]. Wagner also teaches the use of multiple biomarkers to determine if a patient has responded to treatment, and if the response will be sustained, in which the levels of the biomarkers are determined prior to initiation of anti-TNF therapy and at a later time point after initiation of the therapy (e.g., at week-14), wherein a change in the levels of the biomarkers predict the clinical response or non-response to the anti-TNF treatment [0013] [0059-0062]. Wagner teaches that the levels of the biomarkers are determined in serum samples obtained from PsA patients by using multiplex analysis or single analyte ELISA (p. 12, Example 1), and the biomarkers include, e.g., CRP, EGF, IL-6, LEP, MMP-3 and VCAM-1 (p. 12, Table 2; and [0174]). Wagner teaches that at baseline, there were multiple significant associations between biomarker levels and biometric or clinical characteristics of sex, weight, age, baseline CRP, baseline swollen joint count (SJC.bl), and tender joint count at baseline (TJC.bl) found by robust linear regression analysis [0188]. Wagner teaches that the quantitative data obtained from the biomarkers are combined with other dataset components from clinical variables and subjected to an analytic process using a learning algorithm, i.e., inputted into a predictive model; and the analytical process can be used to classify a test subject into one of the two or more phenotypic classes (e.g., a patient predicted to respond to anti-TNF therapy or a patient who will not respond) [0065] [0067] [0075]. Wagner teaches that DAS28 (Disease Activity Index Score using 28 joints) is used as the clinical outcome component of the model [0083]; and DAS28 is a statistically derived index combining tender joints (28 joints), swollen joints (28 joints), CRP, and Global Health (GH), which is defined as follows:
DAS28=0.56*SQRT(TEN28)+0.28*SQRT(SW28)+0.36*Ln(CRP+1)+0.014*GH+0.96 [0147].
Therefore, Wagner anticipates the instant claims.
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.
Claims 45-47, 50, 58-59 and 62-64 are further rejected under 35 U.S.C. 103, as being unpatentable over Wagner et al. (US 2012/0178100 A1), in view of Connolly et al. (Arthritis Rneum., 2012, Vol. 64(4):1035-1045) (reference provided previously).
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.
Wagner teaches as set forth above. Wagner, however, does not teach including serum amyloid A1 (SAA1) (the elected species) in the biomarkers.
Connolly teaches the relationship between acute-phase serum amyloid A (A- SAA) and joint destruction in inflammatory arthritis. Connolly teaches that elevated serum A-SAA levels were significantly correlated with joint destruction in rheumatoid arthritis and psoriatic arthritis patients. The A-SAA disclosed in Connolly meets the limitation of SAA1 of the instant claims (see Office Action of the parent case 15/938,728, mailed 04/14/2021, at the bridging paragraph of pages 6-7).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Wagner with Connolly to include A-SAA in the biomarkers for diagnosing the disease activity and predicting the response of a PsA patient to anti-TNF therapy. One of ordinary skill in the art would have been motivated to do so, because Wagner teaches generating protein level data of a plurality of biomarkers in serum samples obtained from patients having PsA and predicting the response of a PsA patient to anti-TNF therapy, and Connolly further teaches that elevated serum A-SAA levels were significantly correlated with joint destruction in PsA patients. Therefore, the combined teachings provide a reasonable expectation of success in diagnosing and treating the patients with PsA.
Claim 60 is further rejected under 35 U.S.C. 103, as being unpatentable over Wagner et al. (US 2012/0178100 A1), in view of Breiman et al. (Journal of the Royal Statistical Society, Series B (Methodological) Vol. 59, No. 1 (1997), pp. 3-54).
Wagner teaches as set forth above. Wagner, however, does not teach using the CW-Lasso method to calculate the predictable values in the interpretation function.
Breiman teaches using the CW-Lasso method to incorporate multiple response variables, e.g., components of DAS (including TJC28, SJC28 and GH) to obtain predicted values with improved predictive accuracy.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the CW-Lasso method taught by Breiman to calculate PsA disease activity score. One of ordinary skill in the art would have been motivated to do so, because Wagner teaches generating protein level data of a plurality of biomarkers and quantitating clinical assessment (e.g., TJC28, SJC28 and GH) to thereby obtain predicting values of PsA disease activity, and Breiman teaches using the CW-Lasso method to incorporate multiple response variables, e.g., the DAS components (including TJC28, SJC28 and GH) to obtain predicted values with improved predictive accuracy. Therefore, the combined teachings provide a reasonable expectation of success in diagnosing and treating the patients with PsA.
Claim 61 is further rejected under 35 U.S.C. 103, as being unpatentable over Wagner et al. (US 2012/0178100 A1), in view of Centola et al. (PLoS ONE, 2013, Vol. 8(4):e60635).
Wagner teaches as set forth above. Wagner, however, does not teach wherein the interpretation function is calculated by using the formula:
score= ((0.56x(predicted TJC28)0.5+ 0.28x(predicted SJC28)0.5 + 0.36xlog(CRPx10-6+1) + (0.14x(predicted PGA) + 0.96)x10.53) + 1.
Centola teaches quantitating joint damage and inflammation to assess disease activity of rheumatoid arthritis by using the same 12 biomarkers and assessing the same 28 joints. Centola teaches that the score for a multi-biomarker disease activity (MBDA) is calculated using the algorithm:
MBDA Score = round (DAS28-CRP * 10.53 + 1)
wherein DAS28-CRP = 0:56 * sqrt(TJC28) + 0.28 * sqrt(SJC28) + 0.14 * PG +0.36 * In(CRP + 1) + 0.96 (p. 8, col. 2, top paragraph).
Centola teaches the predicted values of TJC28, SJC28 and PG (which are the same as the PTJC, PSJC and PPGHA used in the claimed formula) (see Centola at p. 8, col. 2, top paragraph, and paragraph [00158] of the instant application).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the formula taught by Centola to calculate MBDA score in PsA disease. One of ordinary skill in the art would have been motivated to do so, because Wagner teaches generating protein level data of a plurality of biomarkers and quantitating clinical assessment (e.g., TJC28, SJC28 and GH) to thereby obtain predicting values of PsA disease activity, and Centola teaches an algorism for quantitating a multi-biomarker disease activity (MBDA) in rheumatoid arthritis by using the same 12 biomarkers to assess joint damage and inflammation in the same 28 joints. Therefore, the combined teachings provide a reasonable expectation of success in diagnosing and treating the patients with PsA.
Conclusion
NO CLAIM IS ALLOWED.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Xiaozhen Xie, whose telephone number is 571-272-5569. The examiner can normally be reached on M-F, 8:30-5.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Vanessa L. Ford, can be reached on 571-272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/XIAOZHEN XIE/Primary Examiner, Art Unit 1674
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