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 .
Priority
The present application was filed on 07/22/2021. Acknowledgment is made of the present application as a proper National Stage (371) entry of PCT/US2020/015040, filed on 07/24/2020, which claims benefit of U.S. Provisional Patent Application 62/796,765 filed on 01/25/2019.
Status of the Claims
Claims 2-3 and 16-19 are cancelled. Claims 7-15 are withdrawn. Claims 1 and 4-6 are examining herein.
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.
Claim(s) 1, 4 and 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tureci et al. (A novel tumor associated leucine zipper protein targeting to sites of gene transcription and splicing, Oncogene (2002) 21, 3879 ± 3888, IDS filed 11/30/2021) as evidenced by Viphakone et al. (Luzp4 defines a new mRNA export pathway in cancer cells, Nucleic Acids Research, 2015, Vol. 43, No. 4, IDS filed 11/30/2021), in view of Mayo (Paraneoplastic syndromes of the nervous system 2017, PTO-892 dated 10/01/2025).
Regarding claims 1, 4 and 6, Tureci teaches a method to detect the prevalence of circulating anti-CT-8/HOM-TES-85 IgG autoantibodies in a biological fluid (see page 3880, col.2 and page 3881-3882 col.1). As evidenced by Viphakone, CT-8/HOM-TES-85 is also called Luzp4 (see page 2357 col.1 par.3). Therefore, the method taught by Tureci teaches detecting Luzp4/Luzp4-specific autoantibody complex in a biological sample from a human.
The method comprises contacting a biological sample from a human having a germ cell tumor with a leucine zipper protein 4 (LUZP4) polypeptide (see page 3880-3881 Screening of sera for circulating autoantibodies against CT-8/HOM-TES-85: teaching that “sera of patients and healthy controls were screened”, wherein patients were patients with ovarian cancer, with seminoma and with other types of cancer; see page 3886 col.1 par.5: “recombinant and purified CT-8/HOM-TES-85 protein in coating buffer was absorbed to Maxisorp microwell plates”, and serum was then added into the well).
Tureci teaches detecting the presence or absence of a LUZP4/LUZP4-antibody complex (see page 3886 Screening of sera for circulating autoantibodies against CT-8/HOM-TES-85 section par.1-2: teaching that the phage immune-screening assay and ELISA was used to detect the complex). A positive reaction was defined as an OD value of a 1:400 diluted serum that exceeded the mean OD value of sera from CT-8/HOM-TES-85 seronegative donors by three standard deviations. As a reference, sera from 12 donors being CT-8/HOM-TES-85 negative in the phage assay were used. See page 3886 column 2 paragraph 1.
Tureci shows that the Luzp4/Luzp4-specific autoantibody complex was detected in patients having a germ cell tumor (see page 3881-3882: “One of seven patients with ovarian cancer and one additional patient out of 14 patients with seminoma had a detectable serum reactivity to CT-8/HOM-TES-85, while sera from 50 controls and patients suffering from other types of cancer were negative.”)
Tureci teaches that the primary intention of identifying of cancer derived gene products was to identify new potential targets for immunotherapeutical interventions (Tureci page 3879 col.2 par.1).
However, Tureci does not teaches detecting Luzp4/Luzp4-specific autoantibody complex from human having or suspected of having, a germ cell tumor-associated paraneoplastic neurological syndrome. Tureci does not teach administering an immunosuppressive therapy to said human.
Mayo teaches that paraneoplastic syndromes of the nervous system are a group of uncommon disorders that develop in some people who have cancer. The paraneoplastic syndromes of the nervous system occur when cancer-fighting agents of the immune system also attack parts of the brain, spinal cord, peripheral nerves or muscle (see page 1). The paraneoplastic syndromes of the nervous system occur more often in people with cancers of the lung, ovary, breast, testis or lymphatic system (see page 5).
Mayo also discloses that treatment of neurological paraneoplastic syndromes involves treating the cancer and, in some cases, suppressing the immune response that's causing your signs and symptoms. To stop your immune system from attacking your nervous system, corticosteroids or immunosuppressants can be used. See page 9.
Given the teachings of Tureci and Mayo, before effective filling date of the claimed invention, it is obvious to one having skill in the art to know that the method of Tureci encompasses the measurement of the presence of the Luzp4/Luzp4-specific autoantibody complex in a human suspected of having a germ cell tumor-associated paraneoplastic neurological syndrome because Tureci teaches measuring the Luzp4/Luzp4-specific autoantibody complex in patients with germ cell tumor, and Mayo teaches that paraneoplastic syndromes of the nervous system occur more often in people with ovarian and testis cancer (i.e. germ cell tumor) as taught by Mayo (see page 5).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to administer an immunosuppressive therapy to human having the presence of the said complex because Tureci teaches that the primary intention of identifying of cancer derived gene products was to identify new potential targets for immunotherapeutical interventions (Tureci page 3879 col.2 par.1) and Mayo also teaches that treatment of neurological paraneoplastic syndromes involves treating the cancer and, in some cases, suppressing the immune response to stop the immune system from attacking the nervous system (see Mayo page 9).
One having an ordinary skill in the art would have had a reasonable expectation of success in combining Tureci and Mayo because Tureci and Mayo teach that immunotherapeutical interventions can be used to treat patient with cancer and cancer-related neurological paraneoplastic syndromes (see Tureci page 3879 col.2 par.1 and Mayo page 9).
Claim(s) 5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tureci et al. as evidenced by Viphakone et al. in view of Mayo, as applied to claim 1, further in view of Old et al. (US20030180298).
As to claim 5, Tureci, Viphakone and Mayo teach the invention as discussed above. Tureci does not teach the method comprising a Western blot to detect said complex.
Old provides the diagnosis, monitoring, research, or treatment of conditions characterized by the expression of one or more Cancer Testis (CT) antigens (see Abstract). Old particularly discloses a test for detecting levels of circulating antibodies against the CT-antigen (see par.211) using recombinant CT antigen (see Example 4, par.3076-307). It is noted that LUZP4 is characteristic for genes of the cancer/testis (CT) (also annotated as cancer/germ line) class (see Tureci page 3884 col.1 par.2). Therefore, the teaching of Old is able to apply for detecting autoantibody against the CT-antigen, e.g., LUZP4.
Specifically, Old teaches contacting a sample with CT-antigen (see Example 4 par.306, contacting patients’ sera with CT antigens); detecting the presence or absence of a CT-antigen / CT-antigen -antibody complex (see Example 4 par.306 using ELISA). In addition, the CT-antigen / CT-antigen -antibody complex can also be detected by Western blots (see par.309-310).
It is noted that despite the experimental purposes (e.g., detecting CT-antigen or anti-CT-antigen antibody), the presence or absence of a CT-antigen / CT-antigen antibody complex can be detected by an immunoassay, e.g., either ELISA or Western blot as taught by Old (see par.306, and 309-310).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the ELISA method taught by Tureci for the Western blot taught by Old for the predictable result of detecting CT antigen/ CT-antigen antibody complex (e.g., LUZP4/LUZP4 antibody complex) because both ELISA and Western blot are immunoassay based on a formation of the CT antigen with its specific antibody, so both methods are functionally equivalent. Therefore, exchanging the methods of detecting an antibody of interest taught by Tureci (e.g., phage assay or ELISA), or taught by Old (e.g., ELISA or Western blots) would result in a predictable outcome.
Response to Arguments
Applicant’s arguments, see Remarks, filed 12/29/2025, have been fully considered but not persuasive.
Applicant, in page 6 of Remarks, argued that Tureci merely supported the classification of CT-8/HOM-TES-85 (which is Luzp4) as a tumor associated antigen because the antigen was absent from healthy tissues (except for testis) but expressed in a wide range of different human neoplasms and eliciting tumor associated antibody responses. However, Tureci did not teach that tumor associated CT-8/HOM-TES-85-specific antibodies have any relationship with tumor-associated paraneoplastic neurological syndromes.
Examiner respectfully disagrees. Examiner does not rely on Tureci to teach a germ cell tumor – associated paraneoplastic syndromes. Examiner relies on Tureci to teach that CT-8/HOM-TES-85 (which is Luzp4) fulfils the criteria of a tumor associated antigen. Tureci shows that the CT-8/HOM-TES-85-specific antibodies are detected in patients with ovarian and seminoma cancers, which are also called germ cell tumor, but are not detected in patients with other types of cancer or in healthy controls (see Tureci pages 3881-3882). Therefore, Tureci supports the relationship between the CT-8/HOM-TES-85-specific antibodies and germ cell tumor.
Applicant, in page 6 of Remarks, argued that Mayo did not remedy the deficiencies of Tureci because Mayo did not teach that paraneoplastic syndromes have any relation to tumor associated antigen-specific antibodies, let alone that LUZP4-specifc autoantibodies are associated with such syndromes.
Examiner respectfully disagrees. Examiner does not rely on Mayo to teach the relationship between tumor associated antigen-specific autoantibodies and paraneoplastic neurological syndromes. Examiner relies on Mayo to teach that paraneoplastic syndromes of the nervous system are a group of uncommon disorders that develop in some people who have cancer (see page 1). While any cancer may be associated with a paraneoplastic syndrome of the nervous system, the paraneoplastic syndromes of the nervous system occur more often in people with cancers of the lung, ovary, breast, testis or lymphatic system (see page 5). Therefore, Mayo supports the relationship between a germ cell tumor and paraneoplastic syndromes of the nervous system.
Applicant, in page 6 of Remarks, argued that the combination of cited references did not teach or suggest that a person having ordinary skill in the art should perform a method including (a) contacting a biological sample from a human having, or suspected of having, a germ cell tumor-associated paraneoplastic neurological syndrome with a LUZP4 polypeptide to form a LUZP4/LUZP4-specific autoantibody complex if the biological sample contains LUZP4-specific autoantibodies, (b) detecting the presence of the complex, and ( c) based on the presence of the complex, administering an immunosuppressive therapy to the human.
Examiner respectfully disagrees. Tureci teaches the method of detecting the complex of CT-8/HOM-TES-85 and CT-8/HOM-TES-85 specific antibody (i.e., LUZP4/LUZP4-specific autoantibody complex) in the subjects, wherein the subjects are healthy controls, with ovarian and seminoma cancers (i.e., germ cell tumor), and with other types of cancers. Tureci shows that the complex of CT-8/HOM-TES-85 and CT-8/HOM-TES-85-specific antibodies is detected in patients with ovarian and seminoma cancers, but is not detected in patients with other types of cancer or in healthy controls. As taught by Mayo, the subjects with germ cell tumor has a high risk of developing paraneoplastic neurological syndrome.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to know that the method of Tureci encompasses the measurement of the presence of the Luzp4/Luzp4-specific autoantibody complex in a human suspected of having a germ cell tumor-associated paraneoplastic neurological syndrome because Tureci teaches measuring the Luzp4/Luzp4-specific autoantibody complex in a human in patients with germ cell tumor, and Mayo teaches that paraneoplastic syndromes of the nervous system occurs more often in people with ovarian and testis cancer as taught by Mayo (see page 5).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to administer an immunosuppressive therapy to human having the presence of the said complex because Tureci teaches that the primary intention of identifying of cancer derived gene products was to identify new potential targets for immunotherapeutical interventions (Tureci page 3879 col.2 par.1) and Mayo also teaches that treatment of neurological paraneoplastic syndromes involves treating the cancer and, in some cases, suppressing the immune response to stop the immune system from attacking the nervous system (see Mayo page 9).
One having an ordinary skill in the art would have had a reasonable expectation of success in combining Tureci and Mayo because Tureci and Mayo teach that immunotherapeutical interventions can be used to treat patient with cancer and cancer-related neurological paraneoplastic syndromes (see Tureci page 3879 col.2 par.1 and Mayo page 9).
Conclusion
All claims are rejected.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHAU N.B. TRAN whose telephone number is (571)272-3663. The examiner can normally be reached Mon-Fri 8:30-6:30 CT.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bao-Thuy L Nguyen can be reached on 571-272-0824. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CHAU N.B. TRAN/ Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 February 5, 2026