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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 March 24, 2026 has been entered.
DETAILED ACTION
The amendment filed March 24, 2026 in response to the Office Action of September 24, 2025 is acknowledged and has been entered.
Claims 36-57 have been cancelled.
Claims 58-76 have been added.
Claims 58-76 are pending.
Claims 61, 75 and 76 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions or species, there being no allowable generic or linking claim.
Claims 58-60, and 62-74 are currently under consideration as drawn to the elected invention.
In view of cancellation of previous claims (claim 36-57), the 112(b) rejections set forth in the previous Office Action of September 24, 2025 are hereby withdrawn.
The newly added claims recite specific cancers, specific primers, specific fold-changes (cutoff value) and/or specific antibody for HLA-J (JULY antibody) for the claimed methods. In view of the amendments and Applicant’s arguments, the double patenting rejections and 101 rejection set forth in the previous Office Action of September 24, 2025 are hereby withdrawn.
NEW REJECTION
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.
Claims 58-60, and 62-74 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.
The term “a JULY antibody” in claim 58 renders the claim indefinite. The term “a JULY antibody” is not defined by the claim. Paragraph [0269] of the instant publication (US 2023/0374609 A1) indicates that the JULY antibody is a specific anti-HLA-J antibody. However, the antibody is not disclosed by the specification and the term is not widely used or accepted in the art. One of ordinary skill in the art would not be able to recognize what the JULY antibody is.
The term “a predetermined standard derived” from the HLA-J mRNA in claim 58 renders the claim indefinite. It is not clear to one of ordinary skill in the art what the predetermined standard is or encompassed by said term.
Claim 59 recites the limitation "the cancer" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 60 recites the limitation "the cancer" in line 1. There is insufficient antecedent basis for this limitation in the claim.
The term “a predetermined standard derived” from the HLA-J mRNA in claim 74 renders the claim indefinite. It is not clear to one of ordinary skill in the art what the predetermined standard is or encompassed.
Claims 62-73 are also rejected because these claims depend on claim 58 directly or indirectly.
MAINTAINED/MODIFIED REJECTION
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 58-60, and 62-74 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a WRITTEN DESCRIPTION rejection.
Claim 58 is drawn to a method for diagnosing gynecological cancer, breast cancer, ovarian cancer, and/or bladder cancer comprising: (a) obtaining a sample of a subject; (b) extracting RNA from a first portion of the sample; (c) performing an RT-qPCR assay using a primer pair selected from the group consisting of (i) .. (xiii); thereby determining relative HLA-J mRNA expression using one or more reference genes; (d) preparing a protein lysate from a second portion of the sample and detecting an HLA-J polypeptide by western blot using an anti-HLA-J antibody generated against the C- terminal end of the unique alpha 3 and transmembrane domain of HLA-J, wherein the antibody is a JULY antibody; and (e) wherein the subject is diagnosed as having gynecological cancer, breast cancer, ovarian cancer, and/or bladder cancer when the relative HLA-J mRNA expression is at least 4- fold increased as compared to a negative control, or a predetermined standard derived therefrom, and/or the HLA-J polypeptide is detected in step (d). The specification discloses only HLA-J representing by SEQ ID NO: 1 and SEQ ID NO: 2 which is expressed in ovarian cancer, breast cancer, urothelial/blacker cancer, but does not disclose that the relative HLA-J mRNA expression and/or the HLA-J polypeptide presence can be used to determine whether a subject has the claimed cancer(s) or not. Therefore, the specification provides insufficient written description to support applicant in possession of the claimed method.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include "level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention."
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, disclosure of drawings, or by disclosure of relevant identifying characteristics, for example, structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the
Applicants were in possession of the claimed genus.
Vas-Gath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991), makes clear that: "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Gath at page 1116.)
Regarding the claimed “JULY antibody”, the specification describes the peptide (see Fig. 16, arrow region labeled as “JULY antibody”) used to generate the antibody, but not the structure of the antibody (or antibodies) (see Fug. 16 and [0021] of the instant publication). MPEP 2163 II A 3(a) states: Disclosure of an antigen fully characterized by its structure, formula, chemical name, physical properties, or deposit in a public depository does not, without more, provide an adequate written description of an antibody claimed by its binding affinity to that antigen, even when preparation of such an antibody is routine and conventional. See Amgen Inc. v. Sanofi, 872 F.3d 1367, 1378, 124 USPQ2d 1354, 1361 (Fed. Cir. 2017)("knowledge of the chemical structure of an antigen [does not give] the required kind of structure-identifying information about the corresponding antibodies"); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1351-52, 97 USPQ2d 1870, 1877 (Fed. Cir. 2011)(patent disclosed the antigen the claimed antibody was supposed to bind, but did not disclose any antibodies with the specific claimed properties). Thus, the specification lacks the written description support for the claimed antibody.
By the time the invention was made, it is well established in the art that the formation of an intact antigen-binding site in an antibody usually required the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three "complementarity determining regions" ("CDRs") which provide the majority of the contact residues for the binding of the antibody to its target epitope. Even a single point mutation in HCDR1 region could lead to antibody lose its binding activity (Ni et al., The Protein Journal, 43, pp. 683-696, July 2024, see Abstract). Thus, one ordinary skill in the art would not be able to visualize all antibodies encompassed by the claims, which binds to the specific peptide disclosed in Fig. 16.
Regarding step (e) of claim 58, the present application disclose following:
Example 1: identification of HLA-J as a non-pseudogene with genomic sequence in the human genome. Thus, the sequences (e.g. SEQ ID NO: 1 and SEQ ID NO: 2) present in human genome, not only present in cancer patients but also present in human without tumor.
Example 2: ovarian cancer samples overexpress HLA-J and the expression level is increased after neoadjuvant chemotherapy treatment (Fig. 3). The change in HLA-J mRNA expression has prognostic value in neoadjuvantly treated ovarian cancer patients ([0233], [0234]). The experiment lacks expression analysis for HLA-J in a person without ovarian cancer as a control. Thus, the example does not teach that the relative HLA-J mRNA expression and/or the HLA-J polypeptide presence is indicative for an ovarian cancer in the subject.
Example 3: breast cancer samples express HLA-J and the expression level is increased after neoadjuvant chemotherapy treatment (Fig. 6). The pretreatment levels of HLA-J mRNA expression were correlated with response to chemotherapy ([0256], [0257]). Paragraph [0267] concludes: these results demonstrate that pretherapy HLA-J mRNA expression predicts therapy outcome and effectiveness of chemotherapy in breast cancer, similar to the situation in ovarian cancer (see Example 1). The experiment lacks expression analysis for HLA-J in a person without breast cancer as a control. Thus, the example does not teach that the relative HLA-J mRNA expression and/or the HLA-J polypeptide presence is indicative for a breast cancer in the subject.
Example 4: HLA-J protein can be detected in several cancer samples, including ovarian cancer, breast cancer, urothelial/blacker cancer (Fig. 17, [0269]). HLA-J protein can be also detected in pregnancy sample (Fig. 17, [0269]). HLA-J transcripts are present in all tested samples have HLA-J with or without tumors. Thus, the example does not teach that the relative HLA-J mRNA expression and/or the HLA-J polypeptide presence is indicative for an ovarian cancer, breast cancer, or urothelial/blacker cancer in the subject.
Example 5: HLA-J can’t be detected in invasive bladder cancer before chemotherapy (TUR) and normal tissue (Mapping), but can be detected only in a few cancer samples after chemotherapy (CYS) (Fig. 18, [0023]). None of the mapping samples (0 out of 20) exhibited HLA-J expression. None of TUR samples exhibited HLA-J expression (0 out of 20 cancer samples). Only 3 out of 20 cancer samples after chemotherapy show HLA-J expression (see [0271]). Thus, the example does not teach that the relative HLA-J mRNA expression and/or the HLA-J polypeptide presence is indicative for a bladder cancer in the subject.
Taken together, the specification shows that the claimed HLA-J transcripts are present in normal people without cancer (Example 1 and Example 5), the claimed HLA-J transcripts are not present in some cancers before chemotherapy treatment (Example 5, Fig. 18, [0271]). The Examples do not support that the relative HLA-J mRNA expression and/or the HLA-J polypeptide presence is indicative for any claimed cancer in the subject, or disclose correlation between structure (HLA-J transcript) and function (e.g. to indicate a tumor in a subject). One of ordinary skill in the art would not be able to readily recognize the claimed correlation: wherein the subject is diagnosed as having gynecological cancer, breast cancer, ovarian cancer, and/or bladder cancer when the relative HLA-J mRNA expression is at least 4- fold increased as compared to a negative control, or a predetermined standard derived therefrom, and/or the HLA-J polypeptide is detected in step (d). Claims 59-60, and 62-73 depend on claim 58 and encompass the limitation cited above. Thus, the claims also lack written description support.
Similarly, independent claim 74 recites: “(d) diagnosing the subject as having gynecological cancer, breast cancer, ovarian cancer, and/or bladder cancer when the relative HLA-J mRNA expression is at least 4-fold increased as compared to a negative control or a predetermined standard derived therefrom”, which lacks written description support as set forth above.
Therefore, the specification lacks adequate written description, and one of skill in the art cannot reasonably conclude that Applicant had possession of the claimed invention at the time the instant application was filed.
Response to Arguments
For the rejection under 35 U.S.C. 112(a), Applicant argues:
Applicant respectfully submits that, in view of these limitations, the relevant written-description inquiry is not whether the application contains experimental data for each and every cancer subtype encompassed by the cancers now recited by the claims, but whether the application as filed reasonably conveys possession of the presently claimed diagnostic methods using HLA-J. Here, the application expressly states that the invention relates to the diagnosis of a tumor or cancer, identifies cancer generally, and provides an express list of cancers encompassed by the invention, including breast cancer, ovarian cancer, bladder cancer, and gynecological cancer. See paragraph [0155] of the present application as published, and claims 11-13 of the PCT application.
The application further states that the disclosed nucleic acid molecule and/or protein or peptide may be used in a sample obtained from a subject for diagnosing a tumor and/or for grading a tumor and/or for tumor prognosis. See paragraphs [0158]-[0159] of the present application as published. In addition, the application as filed provides experimental data showing HLA-J expression in multiple distinct cancers, namely ovarian cancer (Examples 2 and 4), breast cancer (Examples 3 and 4), urothelial/bladder cancer (Example 4), and bladder cancer (Example 5), thereby providing representative species across both gynecological and non-gynecological cancers. See paragraph [0157] and paragraphs [0268]-[0270] of the present application as published. In particular, Example 5 reports that none of the "Mapping" samples, i.e., non-tumorous tissue samples from the same cystectomy resectates, exhibited HLA-J-specific mRNA expression, thereby supporting tumor-associated HLA-J expression in the disclosed diagnostic context.
Applicant’s arguments have been fully considered but they are not persuasive. Although the amended claims limited the cancers to gynecological cancer, breast cancer, ovarian cancer, and/or bladder cancer, the specification has not established the correlation between the diagnosis of any claimed cancer and HLA-J mRNA expression at least 4-fold increased and/or HLA-J polypeptide detection. Thus, one of ordinary skill in the art would not recognize that Applicants is in possession of the claimed diagnostic method.
Regarding specific arguments, paragraphs [0158]-[0159] do not provide any data on correlation between the expression of HLA-J (mRNA or polypeptide) and cancer status. Example 2 and Example 3 show high HLA-J mRNA expression level is associated with chemotherapy outcome in ovarian cancer and breast cancer patients. Both examples lack expression analysis for HLA-J in a person without ovarian or breast cancer as a control. Example 4 shows that HLA-J protein can be detected in several cancer samples, including ovarian cancer, breast cancer, urothelial/blacker cancer (Fig. 17, [0269], again no negative controls for these cancer samples). HLA-J protein can be also detected in pregnancy sample (Fig. 17, [0269]). HLA-J transcripts are present in all tested samples have HLA-J with or without tumors. Thus, the results of Examples 2-4 do not support: “wherein the subject is diagnosed as having gynecological cancer, breast cancer, ovarian cancer, and/or bladder cancer when the relative HLA-J mRNA expression is at least 4- fold increased as compared to a negative control, or a predetermined standard derived therefrom, and/or the HLA-J polypeptide is detected in step (d)”.
Example 5 used “mapping” samples, as argued by applicants. However, the results of Example 5 show: 1) none (0 out of 20) of the mapping samples exhibited HLA-J expression; 2) none (0 out of 20) of TUR samples (cancer sample before treatment) exhibited HLA-J expression; 3) only 3 out of 20 cancer samples after chemotherapy show HLA-J expression (see [0271]). Thus, Example 5 does not teach that the relative HLA-J mRNA expression and/or the HLA-J polypeptide presence is indicative for a bladder cancer in the subject.
Take together, the Examples do not support that “wherein the subject is diagnosed as having gynecological cancer, breast cancer, ovarian cancer, and/or bladder cancer when the relative HLA-J mRNA expression is at least 4- fold increased as compared to a negative control, or a predetermined standard derived therefrom, and/or the HLA-J polypeptide is detected in step (d)”. Thus, the rejection is maintained for the reasons of record.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHENG LU whose telephone number is (571)272-0334. The examiner can normally be reached Monday-Friday 8-5.
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/CHENG LU/Examiner, Art Unit 1642
/PETER J REDDIG/Primary Examiner, Art Unit 1646
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