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
1. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 3/20/26 has been entered.
Applicant’s amendment and response filed 3/20/26 is acknowledged and has been entered.
2. Claims 76, 78 and 126-129 are presently being examined. Claims 76 and 129 are independent claims.
3. Applicant’s amendment filed 3/20/26 has overcome the prior rejection of record of claims 76 and 78 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. Applicant has deleted the recitation of SASP.
4. Applicant’s amendment filed 3/20/26 has overcome the prior rejection of record of claims 76 and 78 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.
Applicant has deleted the recitation of SASP and Applicant has amended instant base claim 76 to recite that the step for detecting the presence of senescent cells is in the patient rather than in the sample.
5. Applicant’s amendment filed 3/20/26 has overcome the prior rejection of record of claims 76 and 78 under 35 U.S.C. 102(a)(i) as being anticipated by Pawlak et al. (Thrombosis Research, 2008, 122: 328-335) as evidenced by an admission in the specification at [0004] and by Sun et al. (Cell & Bioscience, 2022, 12:74, pages 1-20).
Applicant has amended the claims to recite wherein the senescent cells in the patient are triggered by oncogene-induced senescence, drug-induced senescence, or replication-induced senescence, thereby further defining the patient population, limitations that the art reference does not teach.
6. The prior rejection of record of claims 76 and 78 as provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 20 of copending Application No.18/535,395 in view of Pawlak et al. (Thrombosis Research, 2008, 122: 328-335) as evidenced by an admission in the specification at [0004] is hereby withdrawn in view of the cancelation of claim 20 in copending application no. 18/535,395 by Applicant.
7. The prior rejection of record of claims 76 and 78 as provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 19 of copending Application No.18/535,012 in view of Pawlak et al. (Thrombosis Research, 2008, 122: 328-335) as evidenced by an admission in the specification at [0004] is hereby withdrawn in view of the cancelation of claim 19 in copending application no. 18/535,012 by Applicant.
8. 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.
9. 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.
10. Claims 76, 78 and 126-129 are rejected under 35 U.S.C. 102(a)(i) as being anticipated by Akdogan et al. (J. Clin Exp. Hepatol., 2019, available online 2/16/18, 9:29-33) as evidenced by Wandrer et al. (Ailment. Pharmacol. Ther. 2018, 48: 270-280), Pizzul et al. (Front. Cell Dev Biol. 2023, doi: 10.3389/cell.2023.1250264, pages 1-7), Paradis et al. (Human Pathol., 2001, 32: 327-332), and Barnard et al. (Gut and Liver, 1/2019, 13(1): 11-15).
Claim interpretation: The specification discloses that soluble uPAR [polypeptide] is a proteolytically cleaved form of the membrane anchored form of uPAR ([00353]). Serum or plasma do not comprise cells and therefore comprise soluble uPAR polypeptide when uPAR is present therein. Regarding dependent claims 128 and 129 and the recitation of “wherein the patient is diagnosed with….”, the said “wherein” clause is not an active step and is therefore being interpreted as the patient had been diagnosed with one of the recited conditions prior to the detecting step, i.e., the said “wherein” clause identifies the patient population from which the sample is obtained. The specification discloses that the reference sample may be obtained from a healthy control subject or may contain a predetermined level of the soluble uPAR polypeptide [0028]. Therefore, the limitation “sample” is being interpreted as a sample from a healthy subject or a sample that contains a predetermined level of soluble uPAR, that is, a sample from a subject or a composition that is constructed to comprise a predetermined level of soluble uPAR. The open transitional phrase “comprising” in the claims opens the claims to encompass additional steps and/or ingredients.
Instant Independent claim 76 recites:
76. (Currently Amended) A method for detecting senescent cells in a patient comprising: detecting the presence of senescent cells in the patient by detecting soluble uPAR (suPAR) polypeptide levels in a biological sample that are at least 5% higher compared to that observed in a reference sample, wherein the biological sample is obtained from the patient, wherein the senescent cells in the patient are triggered by oncogene-induced senescence, drug-induced senescence, or replication-induced senescence.
Instant independent claim 129 recites:
129. (New) A method for detecting senescent cells in a patient comprising:
detecting the presence of senescent cells in the patient by detecting soluble uPAR (suPAR) polypeptide levels in a biological sample that are at least 5% higher compared to that observed in a reference sample, wherein the biological sample is obtained from the patient, wherein the patient is diagnosed with lung fibrosis, Alzheimer’s disease, diabetes, osteoarthritis, liver fibrosis, or chronic kidney disease.
Akdogan et al. teach evaluating uPAR plasma levels (i.e., soluble UPAR) by ELISA in chronic hepatitis B and C patients, wherein the concentrations of uPAR in the samples were determined by comparison to standards having known concentration of soluble uPAR. Akdogan et al. teach that the plasma uPAR levels in patients with chronic hepatitis B and C significantly exceeded those of healthy controls (i.e., this is a comparison of the level of soluble uPAR in each patient sample with the level of soluble uPAR in each healthy control reference sample, a teaching that is encompassed by the open transitional phrase “comprising” in the instant claims) (e.g., abstract). Akdogan et al. teach that plasma uPAR levels in healthy subjects was 2.1 ng/ml, while that in hepatitis B patients was 4.6 ng/ml, and that in hepatitis C patients was 3.8 ng/ml (e.g., Table 2), with the lower individual values for the normal controls versus the individual patients (mild to moderate fibrosis patients as well as severe fibrosis patients) shown in Figures 1 and 2. For example, a 5% increase in 2.1 ng/ml would be 2.2 ng/ml. The patient soluble uPAR levels vastly exceed a 5% increase, as can also be visually seen in Figure 1 and in Figure 2. Akdogan et al. teach that soluble uPAR (suPAR) can be found in serum, produced by proteolytic cleavage from the plasma membrane of cells that express uPAR (page 32 at the first full paragraph). See entire reference.
As pertains to the “wherein” clause recited in instant independent claim 76 that defines the patient populations encompassed by the claim and its dependent claims (i.e., “replication-induced senescence” in claim 76), the following evidentiary references teach that the art reference patient population is the same as is recited in the instant claims.
Evidentiary reference Wandrer et al. teaches that liver fibrosis is an outcome of chronic infection with hepatitis C (such as the patient population taught by Akdogan et al.) and that there is an increase in senescent cells as compared to livers with no or minimal fibrosis. Wandrer et al. teach that cell senescence is a feature that is replication-induced, i.e., reduced telomere length, limited proliferative life span (see entire reference, e.g., abstract, introduction section, section 2.1, page 278 at the first two full paragraphs).
Evidentiary reference Pizzul et al. (Front. Cell Dev Biol. 2023, doi: 10.3389/cell.2023.1250264, pages 1-7) teaches that one of the main triggers of replicative (i.e., replication-induced) senescence is telomere shortening and/or its dysfunction (abstract). See entire reference.
Evidentiary reference Pardis et al. (Human Pathol., 2001, 32: 327-332) teaches that telomere shortening (i.e., replication-induced senescence) contributes to the pathogenesis of liver cirrhosis. Pardis et al. teach that chronic liver damage induced by hepatitis C virus (HCV) infection accelerates telomere shortening and precipitates replicative senescence (see entire reference, especially discussion section).
Evidentiary reference Barnard et al. (Gut and Liver, 1/2019, 13(1): 11-15) teaches that telomere shortening (i.e., replication induced senescence) is a feature in both chromic HCV and HBV infection. Barnard et al. teach that telomere shortening and senescence have been linked to the progression of liver fibrosis. Barnard et al. teach that telomere shortening leading to cellular senescence is supported by the data in a study of fibrosis stage in subjects with HCV infection or with HBV infection(see entire reference, especially section “2”).
Although the art reference is silent about the limitation “wherein the senescent cells in the patient are triggered by…replication-induced senescence” that is recited in instant base claim 76, the cited evidentiary references indicate that replication-induced senescence occurs in chronic hepatitis C patients and in chronic hepatitis B patients (i.e., the patient population is the same as is the patient population recited in the claims), and it does not appear that the claim language or limitations result in a manipulative difference in the method steps when compared to the prior art disclosure. See Bristol-Myers Squibb Company v. Ben Venue Laboratories 58 USPQ2d 1508 (CAFC 2001). “{i}t is a general rule that merely discovering and claiming a new benefit of an old process cannot render the process again patentable.” In re Woodruff, 16 USPQ2d 1934, 1936 (Fed. Cir. 1990). Granting a patent on the discovery of an unknown but inherent function would remove from the public that which is in the public domain by virtue of its inclusion in, or obviousness from, the prior art. In re Baxter Travenol Labs, 21 USPQ2d 1281 (Fed. Cir. 1991). See M.P.E.P. 2145.
11. No claim is allowed.
12. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARIANNE DIBRINO whose telephone number is (571)272-0842. The examiner can normally be reached on M, T, Th, F.
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/Marianne DiBrino/
Marianne DiBrino, Ph.D.
Patent Examiner
Group 1640
Technology Center 1600
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
Prosecution Insights