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
Status of Application, Amendments, and/or Claims
The Information Disclosure Statements (IDS) filed 4 December 2023 have been entered. Applicant’s amendment of the specification filed 31 January 2023 has been entered.
Election/Restriction
Applicant’s election of Group I, claims 1-3, 5, 7-10, 12, 19, 23-27, 31 and 37-39, in the reply received on 4 December 2025 is acknowledged. In the response, Applicant further elected the species of: A-a) wherein the method comprises administering to the subject a recombinant CST6 protein (SEQ ID NO: 3); and D-b) wherein the subject has, or the bone loss is associated with, cancer; and the type of cancer is multiple myeloma. Because Applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.03(a)).
Claims 4, 6, 11, 13-18, 20-22, 28-30, 32-36, 42 and 44-45 are cancelled. Claims 1-3, 5, 7-10, 12, 19, 23-27, 31, 37-41 and 43 are pending. Claims 40-41 and 43 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 1-3, 5, 7-10, 12, 19, 23-27, 31 and 37-39 are under examination to the extent they read on the elected species. Claims 1, 3, 5, 7-8, 23-24 and 39 read on the elected species, and claims 2, 9-10, 12, 19, 25-27, 31 and 37-38 are withdrawn as being drawn to non-elected species.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Drawings
The drawings (Figure 1A) are objected to under 37 CFR 1.83(a) because they fail to show details as described in the specification. FIG. 1A is blurry.
Any structural detail that is essential for a proper understanding of the disclosed invention should be shown in the drawing. MPEP § 608.02(d). Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claims 1, 5, 7-8 and 23-24 are objected to because of the following informalities:
Claims 1, 5, 7-8 and 23-24 use acronyms without first defining what they represent in the independent claims (e.g., “CST6”). While the claims can reference acronyms, the material presented by the acronym must be clearly set forth at the first use of the acronym.
In claim 23, the phrase “a subject having CST6-cancer” should be “a subject having CST6- cancer” or “a subject having CST6-negative cancer”; also, “recombinant CST6” should be “a recombinant CST6 protein (SEQ ID NO: 3)”; further, the phrase “to inhibit cancer cell growth” should be “to inhibit cancer cell growth and bone loss”.
Appropriate correction is required.
Claim Rejections - 35 USC § 102
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 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.
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 1 and 3 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jin et al. (Cell Res., 2012, Vol. 22(9):1356-1373) (reference provided previously).
Jin teaches that secreted cystatin E/M (CST6) is a bona fide suppressor of breast cancer osteolytic metastasis (see Abstract). Jin discloses an in vivo study in which a retroviral plasmid expressing human CST6 was introduced into the SCP2 breast cancer cells, and the ectopic expression of CST6 greatly impaired primary tumor growth and rescued mice from overt osteolytic metastasis in a xenograft mouse model, whereas control SCP2 cells resulted in severe osteolytic bone lesions and massive bone destruction (Figures 6 and 7; and p. 1365, under section “CST6 suppresses breast cancer bone metastasis”).
Therefore, Jin anticipates the instant claims.
Claims 1 and 7-8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ni et al. (US 2002/0052476 A1, Pub. Date: May 2, 2002).
Ni teaches methods for utilizing a human CysE polypeptide for treating osteoporosis, tumor metastases, and other diseases (see Abstract). Ni teaches the amino acid sequence of the human CysE polypeptide, which is identical to SEQ ID NO: 3 of the present application (see sequence alignment attached). The patients treated by Ni, e.g., those having osteoporosis or tumor metastases, meet the limitation as in need of inhibiting cancer cell growth or bone loss. Ni teaches that the CysE polypeptide can be a fusion protein, e.g., combined with the constant domain of immunoglobulins (IgG), to increase in vivo half-life [0095].
Therefore, Ni 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 of this title, 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.
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.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Jin et al., as applied to claims 1 and 3 above, and further in view of Rivenbark et al. (Exp. Mol. Pathol., 2007, Vol. 83(2):188–197).
Jin teaches as set forth above. Jin, however, does not teach wherein the cancer does not express CST6 (claims 5).
Rivenbark teaches that CST6 is a breast tumor suppressor gene that is expressed in normal breast epithelium, but is epigenetically silenced as a consequence of promoter hypermethylation in metastatic breast cancer cell lines (see abstract). Rivenbark teaches that methylation-dependent epigenetic silencing of CST6 represents an important mechanism for loss of CST6 during breast tumorigenesis and/or progression to metastasis (see Abstract).
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 method taught by Jin to treat breast cancer that does not express CST6. One of ordinary skill in the art would have been motivated to do so, because Jin teaches that administering CST6 by recombinant expression can inhibit or reduce osteolytic metastasis of breast cancer, and Rivenbark further teaches that loss of CST6 expression correlates with breast cancer progression to metastasis. Therefore, the combined teachings provide a reasonable expectation of success in treating the cancer.
Claims 7-8 are rejected under 35 U.S.C. 103 as being unpatentable over Jin et al., as applied to claims 1 and 3 above, and further in view of Ni et al. (US 2002/0052476 A1).
Jin teaches as set forth above. Jin, however, does not teach administering a recombinant CST6 protein set forth in SEQ ID NO: 3 (claim 7), nor teaches linking the recombinant CST6 protein to a tag (claim 8).
Ni teaches a human CysE polypeptide identical to SEQ ID NO: 3 of the present application which is useful for treating osteoporosis, tumor metastases, and other diseases (see Abstract). Ni teaches that the CysE polypeptide can be a fusion protein, e.g., combined with the constant domain of immunoglobulins (IgG), to increase in vivo half-life [0095].
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 human CysE polypeptide taught by Ni to inhibit or reduce osteolytic metastasis of breast cancer in a subject. One of ordinary skill in the art would have been motivated to do so, because Jin teaches that administering CST6 by recombinant expression can inhibit or reduce osteolytic metastasis of breast cancer, and Ni teaches a human CysE polypeptide useful for treating osteoporosis, tumor metastases, and other diseases. Therefore, the combined teachings provide a reasonable expectation of success in treating the subject.
Claims 23-24 are rejected under 35 U.S.C. 103 as being unpatentable over Jin et al., in view of Rivenbark et al., and further in view of Ni et al. (US 2002/0052476 A1).
Jin teaches as set forth above. Jin, however, does not teach treating a subject having CST6- cancer, nor teaches administering a recombinant CST6 protein set forth in SEQ ID NO: 3 and detecting the lack of expression of CST6 in the cancer cells prior to administering the CST6 (claims 23-24).
Rivenbark teaches that CST6 is a breast tumor suppressor gene that is expressed in normal breast epithelium, but is epigenetically silenced as a consequence of promoter hypermethylation in metastatic breast cancer cell lines (see abstract). Rivenbark studied the expression and methylation status of CST6 in primary breast tumors and lymph node metastases and found that methylation-dependent silencing of CST6 occurs in a subset of primary breast cancers, but more frequently in metastatic lesions (see Abstract and first two sections in “Results”). Rivenbark suggests that methylation-dependent epigenetic silencing of CST6 represents an important mechanism for loss of CST6 during breast tumorigenesis and/or progression to metastasis (see Abstract).
Ni further teaches a human CysE polypeptide identical to SEQ ID NO: 3 of the present application which is useful for treating osteoporosis, tumor metastases, and other diseases (see Abstract).
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 human CysE polypeptide taught by Ni to inhibit or reduce osteolytic metastasis of breast cancer that does not express CST6 in a subject. One of ordinary skill in the art would have been motivated to do so, because Jin teaches that administering CST6 by recombinant expression can inhibit osteolytic metastasis of breast cancer, Rivenbark further teaches that loss of CST6 expression correlates with breast cancer progression to metastasis, and Ni furthermore teaches a human CysE polypeptide useful for treating osteoporosis, tumor metastases, and other diseases. Therefore, the combined teachings provide a reasonable expectation of success in treating the subject.
Claim 39 is rejected under 35 U.S.C. 103 as being unpatentable over Jin et al., Rivenbark et al., and Ni et al. (US 2002/0052476 A1), and further in view of Lee et al. (J. Drug Deliv., 2012, Vol. 2012, Article ID 915375, 17 pages).
Jin, Rivenbark, and Ni teach as set forth above. These reference, however, do not teach further administering an anti-cancer therapy to the subject (claim 39).
Lee teaches that disseminated metastatic breast cancer needs aggressive treatment due to its reduced response to anticancer treatment and hence low survival and quality of life (see Abstract). Lee teaches that for better therapeutic effectiveness, combination anticancer treatment has long been adopted in clinics; when multiple drugs with different molecular targets are applied, the cancer adaptation process such as cancer cell mutations can be delayed (p. 2, 1st paragraph under section “2. Combination Therapy in Metastatic Breast Cancer”).
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 CST6 in combination with another anti-cancer therapy to treat a subject having metastatic breast cancer that has lost CST6 expression. One of ordinary skill in the art would have been motivated to do so, because Jin, Rivenbark, and Ni teach and suggest administering a recombinant CST6 protein to treat a subject having metastatic breast cancer that has lost CST6 expression, and Lee teaches using combination anticancer treatment for metastatic breast cancer to achieve better therapeutic effectiveness. Therefore, the combined teachings provide a reasonable expectation of success in treating the subject.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Ni et al. (US 2002/0052476 A1), as applied to claims 1 and 7-8 above, and further in view of Tosi, P. (Scientifica, 2013, Volume 2013(1), Article ID 104546, 12 pages).
Ni teaches as set forth above. Ni, however, does not teach wherein the subject has bone loss associated with multiple myeloma (the elected species) (claim 3).
Tosi teaches that bone disease is observed in almost 80% of newly diagnosed symptomatic multiple myeloma patients, and spine is the bone site that is more frequently affected by myeloma-induced osteoporosis, osteolyses, or compression fractures (see Abstract).
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 method taught by Ni to inhibit or reduce bone disease, e.g., osteoporosis, osteolyses, or compression fractures, in patients having multiple myeloma. One of ordinary skill in the art would have been motivated to do so, because Ni teaches that CST6 can be used for treating osteoporosis and tumor metastases, and Tosi teaches that patients having multiple myeloma frequently suffer from myeloma-induced osteoporosis, osteolyses, or compression fractures. Therefore, the combined teachings provide a reasonable expectation of success in treating the patients.
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