DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicant’s reply filed on 9/14/2026 is acknowledged. Claims 9, 11, 12, 29, 31, 35 and 37-50 are pending. Claims 1-8, 10, 13-28, 30, 32-34 and 36 are canceled. Claim 35 and 38-50 are withdrawn. Claim 43 has been amended.
3. In the reply filed on 3/18/2025, applicant elected the species of (i) antibody or antigen binding fragment thereof, (ii) 3-2 antibody comprising the following 6 CDR sequences: SEQ ID NO: 14 (VH-CDR1), SEQ ID NO: 15 (VH-CDR2), SEQ ID NO: 16 (VH-CDR3), SEQ ID NO: 26 (VL- CDR1), SEQ ID NO: 27 (VL-CDR2), and SEQ ID NO: 28 (VL-CDR3), (iii) FAM19A5 protein level, (iv) PD-1, (v) melanoma, and (vi) SEQ ID NO: 6.
4. Claims 9, 11, 12, 29, 31 and 37 are under examination.
Information Disclosure Statement
5. The information disclosure statement (IDS) submitted on 9/14/2026 has been considered by the examiner.
Priority
6. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e)
or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not
complied with one or more conditions for receiving the benefit of an earlier filing date
under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention
which is also disclosed in the prior application (the parent or original nonprovisional
application or provisional application). The disclosure of the invention in the parent
application and in the later-filed application must be sufficient to comply with the
requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112,
except for the best mode requirement. See Transco Products, Inc. v. Performance
Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application Nos. 62,582,886 and
62/525,633 fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
Independent claim 9 recite “wherein the cancer comprises a melanoma, pancreatic cancer, breast cancer, lymphoma, carcinoma, sarcoma, lung cancer, kidney cancer, prostate cancer, fibrosarcoma, colon adenocarcinoma, liver cancer, ovarian cancer, or any combinations thereof”. Application Nos. 62,582,886 and 62/525,633 do not mention melanoma, prostate cancer, fibrosarcoma, colon adenocarcinoma and ovarian cancer. Therefore, claims 9, 11, 12, 29, 31 and 37 are not entitled to the
benefit of the filing dates of Application Nos. 62,582,886 and 62,525,633. The effective filing date of claims 11, 12, 14, 15, 29-31 and 35-36 is the filing date of Application No.
62,597,920 (12/17/2017).
Rejection Withdrawn
7. The rejection of claims 9, 11, 29, 31 and 37 under 35 U.S.C. 103 as being unpatentable over O’Donnell et al (US 2016/0060705A1, pub. date: 3/3/2016, PTO 892 dated 4/2/2025), in view of Seong et al. (US 2015/0118230A1, pub. date: 4/30/2015, PTO 892 dated 4/2/2025), further in view of US 12,072,339 (Seong et al., date of patent: 8/27/2024, effectively filed date: 10/2/2017) is withdrawn in view of applicant’s statement under U.S.C. 102(b)(2)(C).
Rejection Maintained
Claim Rejections - 35 USC § 103
8. 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.
9. Claims 9, 11, 29 and 31 remain rejected under 35 U.S.C. 103 as being
unpatentable over O’Donnell et al (US 2016/0060705A1, pub. date: 3/3/2016, PTO 892 dated 4/2/2025), in view of Seong et al. (US 2015/0118230A1, pub. date: 4/30/2015, PTO 892 dated 4/2/2025).
Regarding claim 9, O’Donnell teaches a method of diagnosing an individual as having a DNA damage response deficient (DDRD) cancer comprising; a. measuring expression levels of at least five genes in a test sample of tumor cells obtained from the individual, comparing the expression levels of the at least five genes to a threshold score, and if the expression levels exceed a threshold score based on the same genes, treating the individual with a DNA-damage therapeutic agent, wherein at least five of the genes include FAM19A5 (claims), detecting expression of genes is by immunoassay method using an antibody ([0115]), wherein the cancer is selected from melanoma, colon cancer, breast cancer, and ovarian cancer (claims). O’Donnell teaches using polyclonal antibodies to detect the at least 5 genes including FAM19A5 ([0114], [0115]).
Regarding claim 11, O’Donnell teaches that if the expression levels exceed a threshold score based on the same genes, treating the individual with a DNA-damage therapeutic agent (a chemotherapeutic agent, claims 44 and 45).
Regarding claim 29, O’Donnell teaches that sample is tissue [0058]).
Regarding claim 9, O’Donnell does not specifically disclose comparing the expression level of a biomarker to a level of FAM19A5 detected in cancer sample to a level in healthy or normal individuals. However, O’Donnell teaches comparing the expression level of a biomarker to a level of the biomarker that is typically detected in similar biological samples from healthy or normal individuals ([0050] and [0052])).
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 have detected the level of FAM19A5 in cancer including melanoma and compared the detected level to a corresponding level from a normal subject in view of O’Donnell. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success because O’Connell teaches that when a biomarker indicates or is a sign of an abnormal process disease or other condition in an individual, that biomarker is generally described as being either over-expressed or under-expressed as compared to an expression level of the biomarker that is typically detected in similar biological samples from healthy or normal individuals ([0050] and [0052]).
Regarding claims 9 and 31, O’Donnell does not teach detecting FAM19A5 using a humanized antibody or an antibody fragment such as a Fab.
Seong et al teaches detecting a level of FAM19A5 protein in serum of mice having brain injury using an anti-FAM19A5 antibody, and comparing the level to corresponding level from normal mice ([0918]). Seong et al teaches that the antibody can be humanized anti-FAM19A5 antibody ([0082]),or an antigen binding fragment thereof, e.g. Fab, Fab’, scFv ([0083]), or polyclonal antibodies ([0082]).
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 have detected FAM19A5 protein using a humanized anti-FAM19A5 antibody or an antigen binding fragment such as a fab in view of Seong. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success because Seong et al teaches detecting a level of FAM19A5 protein in serum using an anti-FAM19A5 antibody and the anti-FAM19A5 can be a humanized antibody, or an antigen binding fragment such as Fab.
Applicant’s Arguments
The response states that that the Examiner's characterization of claim 9 is legally improper. When considered in its entirety, claim 9 requires a constellation of specific elements: (i) a method directed specifically to FAM19A5 protein - not mRNA, and not a composite multi-gene score; (ii) measurement in a subject having a cancer; (iii) using an agent that specifically binds FAM19A5 - namely, a humanized or chimeric anti-FAM19A5 antibody; and (iv) comparison of the measured FAM19A5 protein level to a corresponding level from a normal subject. Each of these elements must be considered in the obviousness analysis. The Examiner's reduction of this multi-element method to a single generic detection step improperly fragments the claim and, as a consequence, leads to an incomplete and legally deficient obviousness analysis.
Additionally, a skilled artisan reading the present application would understand that, in some aspects, by measuring and comparing the FAM19A5 protein expression to a normal subject, it would be possible to identify subjects that are afflicted with a cancer (see, e.g., Example 6).
The response states that O'Donnell's purpose is fundamentally different from that of claim 9. In O'Donnell's DDRD classifier was developed to predict whether a cancer patient will respond to DNA-damage therapeutic agents - it is a chemotherapy response prediction tool, designed to identify. FAM19A5 appears in O'Donnell's classifier at rank 26 out of 44 genes, carrying one of the smallest positive weights in the panel (~0.010, Table 2B) and no specific determination of any kind is drawn from FAM19A5 expression alone. Claim 9, by contrast, is directed to a wholly different set of method steps and a wholly different purpose: specifically measuring FAM19A5 protein in a cancer subject's biological sample using a humanized or chimeric anti-FAM19A5 antibody and comparing the measured FAM19A5 protein level to a corresponding level from a normal subject. FAM19A5 protein is the specific and central analyte of the claimed method. A skilled artisan reading the present application would understand that, in some aspects, by specifically measuring and comparing the FAM19A5 protein expression to a normal subject, it would be possible to identify subjects that are afflicted with a cancer (see, e.g., Example 6). Applicant respectfully submits that a skilled artisan reading the cited references would not have been able to reasonably recognize such a technical effect of claim 9. Only through the present application would a skilled artisan have been able to arrive at claim 9 with any reasonable expectation of success.
Examiner’s Response
Applicant’s arguments have been carefully considered but are not persuasive. The only active step of claim 9 is detecting whether the FAM19A5 protein level from a biological sample obtained from the subject having a cancer is increased compared to a corresponding level from a normal subject by contacting an antibody with the biological sample of the subject and measuring the FAM19A5 protein level in the biological sample (emphasis added).
O’Donnell teaches measuring expression levels of at least five genes including FAM19A5 in a test sample of tumor cells obtained from the individual, comparing the expression levels of the at least five genes to a threshold score, and if the expression levels exceed a threshold score based on the same genes, treating the individual with a DNA-damage therapeutic agent (claims), wherein measuring expression levels of at least five genes is by immunoassay method using an antibody ([0115]), wherein the cancer is selected from melanoma, colon cancer, breast cancer, and ovarian cancer (claims). O’Donnell teaches using polyclonal antibodies to detect the at least 5 genes including FAM19A5 ([0114], [0115]). Therefore, O’Donnell teaches detecting at least 5 genes including FAM19A5 by detecting protein expression level in a sample of a subject having a cancer using an immunoassay. Although O’Donnell does not specifically disclose comparing the expression level of FAM19A5 detected in cancer sample to a level in healthy or normal individuals, O’Donnell teaches comparing the expression level of a biomarker to a level of the biomarker that is typically detected in similar biological samples from healthy or normal individuals ([0050] and [0052])). One of ordinary skill in the art would have had a reasonable expectation of success to make such comparison.
Applicants arguments that O’Donnell detects multiple genes while instant method detects only FAM19A5 protein are not persuasive. The instant method recites the term “comprising”. The term “comprising” is open, as such the claim does not preclude detecting additional markers.
Applicant’s arguments that the claimed method can identify subjects that are afflicted with a cancer (see, e.g., Example 6) are not persuasive because applicant argued a limitation which is not present in the claims. Furthermore, claim 9 specifically requires detecting FAM19A5 in a sample of a subject having a cancer.
Applicant’s arguments that O'Donnell's purpose is fundamentally different from that of claim 9 are not persuasive. MPEP 2144 IV states “The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006)”
Applicant’s arguments of no reasonable expectation of success are not persuasive. As indicated in the previous office action mailed on 4/13/2026, Narayanan et al. (Cancer Genomics & Proteomics, 2015, 12: 9-20) shows a correlation between mRNA and protein. Narayanan et al. teaches that FAM19A5 mRNA is upregulated in pancreatic cancer (Table IV), and there is a strong correlation between FAM19A5 mRNA and protein expression (Table VI).
For the foregoing reasons, the rejection is deemed proper and is therefore maintained.
10. Claims 9, 11, 12, 29 and 31 remain rejected under 35 U.S.C. 103 as being unpatentable over O’Donnell et al (US 2016/0060705A1, pub. date: 3/3/2016, PTO 892 dated 4/2/2025), in view of Seong et al. (US 2015/0118230A1, pub. date: 4/30/2015, PTO 892 dated 4/2/2025), further in view of Rajan et al. (Human Vaccines & Immunotherapeutics, 2016, 12(9): 2219-2231).
The teachings of O’Donnell and Seong have been set forth above as they apply to claims 9, 11, 29 and 31.
Regarding claim 12, O’Donnell and Seong do not teach treating the subject having a cancer such as melanoma with an anti-cancer drug such as an anti-PD-1 antibody monoclonal antibody.
Rajan et al. teaches that the development of immune checkpoint inhibitors has altered the landscape of treatment of advanced cancers and these drugs are well tolerated and have shown clinical activity against a wide variety of solid tumors and hematological malignancies (abstract). Nivolumab (Opdivo) is an IgG4 antibody that causes immune checkpoint blockade by diminishing inhibitory signaling through the PD-1 pathway. It is approved for treatment of recurrent non-small cell lung cancer, melanoma, and renal cell carcinoma (abstract). Rajan et al. teaches that nivolumab has demonstrated clinical activity and an acceptable safety profile as a single-agent and as part of combination therapy in patients with advanced melanoma (page 2222, column 2).
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 have modified the method of O’Donnell to further treat the subject who has been diagnosed to have cancer including melanoma with an anti-PD-1 antibody in view of Rajan. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success because there is always a motivation to treat cancer once diagnosed and Rajan et al. teaches that nivolumab is approved for treatment of recurrent non-small cell lung cancer, melanoma, and renal cell carcinoma.
Applicant’s Arguments
The response states that as explained above, O'Donnell and Seong (alone or in combination) do not teach nor suggest the subject matter of current claim 9. Rajan is completely silent on FAM19A5. Accordingly, Rajan fails to remedy the deficiencies of both O'Donnell and Seong and therefore, current claims are non-obvious over the combination of O'Donnell, Seong, and Rajan
Examiner’s Response
Applicant’s arguments have been carefully considered but are not persuasive for the same reasons discussed above.
Double Patenting
11. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
12. Claims 9, 11-12, 29, 31 and 37 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 9-15, 19 and 21-28 of copending Application No. 19/029,306 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 9 and 23 of the copending application discloses a method of determining a FAM19A5 protein level or a FAM19A5 mRNA level in a subject having a cancer comprising detecting whether the FAM19A5 protein level or the FAM19A5 mRNA level from a biological sample obtained from the subject is increased compared to a corresponding level from a normal subject by contacting an antagonist against FAM19A5 with the biological sample of the subject and measuring the FAM19A5 protein level or the FAM19A5 mRNA level in the sample, wherein the FAM19A5 antagonist comprises an antibody, or an antigen-binding portion thereof, that specifically binds to the FAM19A5 protein (anti- FAM19A5 antibody).
Claims 1-4, 10-15, 19, 21-22 and 24-28 of the copending application disclose a method of promoting a blood vessel normalization in a tumor of a subject in need thereof, comprising administering to the subject an anti-FAM19A5 antibody or an antigen binding fragment thereof, and a chemotherapeutic agent or a immunotherapeutic agent, wherein the immunotherapeutic agent comprises a monoclonal antibody, chimeric antigen receptor (CAR) T-cell, NK-cell, dendritic cell (DC), adoptive cell transfer (ACT), immune checkpoint modulator, cytokine, cancer vaccine, adjuvant, oncolytic virus, or combination thereof, wherein the monoclonal antibody modulates a signaling molecule selected from the group consisting of PD-1, PD-L1, CTLA-4, IDO, TIM-3, LAG-3, 4-1BB, OX40, MERTK, CD27, GITR,B7.1, TGF-p, BTLA, VISTA, Arginase, MICA, MICB, B7-H4, CD28, CD137, wherein the antigen-binding portion thereof comprises a Fab, Fab', F(ab')2, Fv fragment, single chain Fv (scFv), single-domain antibody (sdAb), or combinations thereof, wherein the anti-FAM19A5 antibody comprises a VH of SEQ ID NO:36 and a VL of SEQ ID NO:40. The amino acid sequences of SEQ ID NO: 36 comprise the 3 CDR sequences recited in claim 37 (i.e. SEQ ID NO: 14 (VH-CDR1), SEQ ID NO: 15 (VH-CDR2), SEQ ID NO: 16 (VH-CDR3). The amino acid sequences of SEQ ID NO: 40 comprise the 3 CDR sequences recited in SEQ ID NO: 26 (VL- CDR1), SEQ ID NO: 27 (VL-CDR2), and SEQ ID NO: 28 (VL-CDR3).
Response to Arguments
In the response, applicant requested that the double patenting rejections be held in abeyance until the claimed subject matter is otherwise deemed allowable.
The rejection is maintained because applicant has not taken any action to resolve the issue.
13. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Roudier et al., The prostate, 76:810-822, 2016. FAM19A5 expression is upregulated in prostate cancer.
Conclusion
14. No claims are allowed.
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.
15. Any inquiry concerning this communication or earlier communications from the examiner should be directed to HONG SANG whose telephone number is (571)272-8145. The examiner can normally be reached Monday-Friday 8am-5pm.
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/HONG SANG/Primary Examiner, Art Unit 1643
Prosecution Insights