Hat waDETAILED 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 .
Application Status
This action is written in response to applicant’s correspondence received 09/03/2026. Claims 1-4,6,8,10-12,20-21,23,25,29-33,35 and 40 are currently pending. Claims 20-21,23,25,29-33,35 and 40 are withdrawn from prosecution as being drawn to non-elected subject matter. Accordingly, claims 1-4,6,8, and 10-12 are examined herein. The restriction requirement mailed 06/03/2026 is still deemed proper. Applicant elected the invention of group I without traverse in the reply filed 09/03/2026.
Objections to the Specification
The use of trade names or marks used in commerce, has been noted in this application:
- Abraxane® (serial no. 2990396)
- TaKaRa Ex Taq™ (serial no. 85270789)
- SYBR™ (serial no. 98151335)
The terms should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (please see page 7). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Rejections - 35 USC § 112(b)
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.
Claim 12 is 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.
Claim 12 contains the trademark/trade name Abraxane® (serial no. 2990396). Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a pharmaceutical composition and, accordingly, the identification/description is indefinite.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-4, 6 and 8 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea/law of nature without significantly more.
Eligibility Step 1 (MPEP 2106.03): Is the claim drawn to a statutory category such as a composition of matter, process, or machine?
Claim 1 is drawn to a process comprising detecting expression of SSR3 in a cancer sample from a subject, and is eligible at step 1.
Eligibility Step 2A Prong One (MPEP 2106.04(II)(A)(1)): Is the claim directed to a judicial exception?
Claim 1 is directed to a method comprising detecting expression of SSR3. The detection step is an observation, which is a mental process which can be performed in the human mind by merely observing the output of a gene measurement assay and determining whether or not SSR3 expression was detected by the assay.
Eligibility Step 2A Prong Two (MPEP 2106.04(d)): Does the claim recite additional elements that integrate the exception into a practical application?
Because the step of administration of a tubulin inhibitor is optional and thus non limiting, the claim does not integrate the exception into a practical application. Additionally, even if the administration is considered limiting for the sake of thorough analysis, the administration of a tubulin inhibitor to a subject is recited at a high level of generality, and is not a particular treatment or prophylaxis in the field of cancer treatment. The term “tubulin inhibitor” broadly describes a class of drugs which are, “used widely in cancer chemotherapy” (Lu et al. An Overview of Tubulin Inhibitors That Interact with the Colchicine Binding Site. Pharm Res (2012) 29:2943–2971.)(§ Introduction, p. 2943). Further, “Tubulin targeting agents have played a key role in cancer treatment since the approval of vincristine by FDA in 1963” (Lu, § Conclusion). Thus, the limitation merely indicates a field of use in which to apply the judicial exception by referring to the relevant pre-existing audience of doctors who use tubulin inhibitors to treat patients suffering from cancer. See MPEP 2106.05(h).
The claim also recites the element of a cancer sample (obtained) from the subject, and the method implicitly requires a) obtaining the sample and b) measuring SSR3 expression. However, these elements amount to insignificant extra-solution activity, i.e., data gathering steps for use in the claimed process of detecting SSR3 expression.
Eligibility Step 2B (MPEP 2106.05): Does the claim include additional elements that are sufficient to amount to significantly more than the judicial exception?
The claim recites or requires additional elements of obtaining a cancer sample from a subject, measuring SSR3 expression, and optionally administering a tubulin inhibitor to the subject. Per MPEP 2106.05(d)(II), the courts have recognized that certain methods of detecting expression in a sample, such as detecting DNA or enzymes in a sample, analyzing DNA to provide sequence information, and/or hybridizing a gene probe, are all routine, well-understood and conventional laboratory techniques. Thus, these elements do not amount to significantly more than the judicial exception.
Regarding claim 2:
Step 1: Claim 2 recites the method of claim 1 (a method comprising detecting expression of SSR3 in a cancer sample from a subject), which is a process.
Step 2A Prong One: The claim recites wherein if the detected expression of SSR3 is greater than a defined baseline level, the subject is administered the tubulin inhibitor. This is directed to both a law of nature, i.e., the expression level of SSR3 in a cancer sample from a subject, and a mental process, i.e., comparing the SSR3 expression level to a baseline and determining whether it is greater. Thus, claim 2 is also directed to a judicial exception.
Step 2A Prong Two: Here, it is relevant to note that the claim recites contingent limitations. The broadest reasonable interpretation of the claim includes two embodiments: one wherein the expression of SSR3 is greater than baseline, and the inhibitor is administered, and one wherein the expression of SSR3 is not greater than baseline, and no action is taken, and no additional elements exist. Thus, for that embodiment, no additional elements exist which may integrate the judicial exception into a practical application. Further, for the embodiment in which SSR3 expression is greater than baseline, the administration of a tubulin inhibitor to the subject, recited at a high level of generality, does not integrate the judicial exception into a practical application for the same reasons described above regarding claim 1.
Step 2B: The claim recites the additional element of administering a tubulin inhibitor to the subject. This does not amount to significantly more for the same reasons described above regarding claim 1.
Regarding claims 3 and 4: These claims are drawn to a process (Step 1) and inherit the judicial exception of claim 1 (Step 2A Prong One). They do not recite any active steps which may integrate the judicial exception into a practical application (Step 2A Prong Two). They recite the additional element of specifying how the cancer sample is obtained (from a biopsy of a solid tumor), and specifying the type of cancer sample. However, these do not amount to significantly more than the judicial exception because obtaining a particular sample via biopsy for use in the method amounts to a mere data gathering step, and further is a routine, well-understood and conventional laboratory technique, as described above.
Regarding claims 6 and 8: These claims are drawn to a process (Step 1) and inherit the judicial exception of claim 1 (Step 2A Prong One). They require a step of administering a tubulin inhibitor which is either a taxane (claim 6) or a vinca alkaloid (claim 8). However, the administration of said compounds does not integrate the judicial exception into a practical application because taxanes and vinca alkaloids belong to broad classes of tubulin targeting agents, recited at a high level of generality, which are routinely used in the field of cancer treatment (see the citations from Lu, above, and Lu. P. 2944, describing “the success of the taxanes and vinca alkaloids”). Thus, the claims are ineligible at Steps 2A Prong Two and at Step 2B for the same reasons described in the rejection of claim 1, above.
Claims 10-12 are not included in this rejection because the administration of a tubulin inhibitor specifically to a glioblastoma via transient blood brain barrier opening is not routine, well-understood and conventional. As stated by Zhang, “Many systemically administered cytotoxic or molecularly targeted therapies that are effective in the treatment of other solid tumors have proven of little benefit in glioma patients due to the presence of the protective BBB…PTX displays one of the most potent anti-glioma effects in-vitro, but is unable to cross the BBB and reach infiltrative glioma cells at meaningful concentrations.” (p. 10). While Zhang reports that ultrasound-mediated BBB disruption has been used to enhance the delivery of other chemotherapeutic agents such as doxorubicin, carboplatin, and temozolomide (p. 2), these drugs are not tubulin inhibitors, and Zhang reports only one other study in which delivery of tubulin inhibitors across the BBB using ultrasound was explored (p. 10). Thus, the evidence suggests that methods comprising administration of a tubulin inhibitor specifically to a glioblastoma via transient blood brain barrier opening is not a routine, well-understood and conventional activity, which integrates the judicial exception into a practical application which is a particular treatment or prophylaxis (Step 2A Prong Two) and amounts to significantly more than the judicial exception (Step 2B).
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-4 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by US PGPUB 20130244256 to Clarke (of record, cited on an IDS, hereinafter ‘Clarke’)
Claim interpretation:
Claim 1 recites an optional step of administering a tubulin inhibitor to the subject. The broadest reasonable interpretation therefore encompasses embodiments which comprise only the step of detecting expression of SSR3 in a cancer sample from a subject.
Claim 2 recites a contingent limitation wherein if the detected expression of SSR3 in the cancer sample is greater than a defined baseline level, the subject is administered the tubulin inhibitor. As a result, the broadest reasonable interpretation of the claim also encompasses an embodiment in which the detected expression of SSR3 is not greater than the defined baseline level, and no further method step is performed.
Regarding claim 1, Clarke teaches a method comprising:(a) detecting expression of signal sequence receptor 3 (SSR3) in a cancer sample from a subject:
[0358] This Example describes how various stem cell cancer markers were identified using microarray screens. The results of these screen are presented in Tables A-N, with the names of the differentially expressed gene names reported in Tables 4-8 (see above). In order to generate gene expression profiles, human breast tumorigenic cells which were initially isolated. A series of samples were accumulated from human breast tumors or normal tissues.
Regarding claim 2, please note that SSR3 is listed in Table 6 as one of the markers detected as downregulated in UPTG (breast tumorigenic; see para [0360] for the explanation of the abbreviation) versus UPNTG (breast non-tumorigenic; Id.), i.e., not greater than a defined baseline in the example described in para [0358].
Regarding claim 3, Clarke teaches wherein the cancer sample is obtained from a biopsy of a solid tumor from the subject (see para [0358] above).
Regarding claim 4, Clarke teaches wherein the cancer is breast cancer (see above).
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
Determining the scope and contents of the prior art.
Ascertaining the differences between the prior art and the claims at issue.
Resolving the level of ordinary skill in the pertinent art.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 10-12 are rejected under 35 U.S.C. 103 as being unpatentable over Clarke as applied to claims 1-4, in view of Zhang (Zhang et al. (2020). Ultrasound-mediated Delivery of Paclitaxel for Glioma: A Comparative Study of Distribution, Toxicity, and Efficacy of Albumin-bound Versus Cremophor Formulations. Clin Cancer Res 26, 477-486.; of record, cited on an IDS), as evidenced by Lim (Lim N., et al., Curation of over 10,000 transcriptomic studies to enable data reuse. Database, 2021.).
Regarding claim 10: Clarke teaches the method of claim 1, from which the instantly rejected claims depend, as described above.
Clarke does not teach the method wherein the subject has glioblastoma and the method comprises administering a tubulin inhibitor to the glioblastoma via transient blood brain barrier opening.
However, Clarke does teach detecting solid tumor stem cells [para [0009]) via detecting expression of multiple genes using an Affymetrix HG-U133 A microarray (para [0360]), which includes SSR3, as evidenced by Lim (see attached). Clarke further states that, “Examples of solid tumors from which solid tumor stem cells can be isolated or enriched for according to the invention include…glioma” (para [0013]). Thus, Clarke teaches a method comprising detecting expression of a SSR3 in a glioma cancer sample from a subject.
Clarke does not teach administering a tubulin inhibitor to the glioblastoma via transient BBB opening.
Zhang teaches administering Abraxane to a glioblastoma via transient BBB opening (Title, p. 3).
Zhang further teaches that, “Ultrasound delivery of paclitaxel across the BBB is a feasible and effective treatment for glioma. ABX is the preferred formulation for further investigation in the clinical setting due to its superior brain penetration and tolerability compared to CrEL-PTX.” (p. 2, Abstract, § Conclusions).
It would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of detecting SSR3 to detect cancer stem cells in a cancer sample from a subject, as taught by Clarke, by adding a step of administering Abraxane to a subject via transient opening of the BBB when the subject is identified as having glioblastoma. The ordinary artisan would have been motivated to do so, and had a reasonable expectation of success, based on Zhang’s teachings that ultrasound delivery of Abraxane across the BBB was a feasible, effective, and preferred treatment.
Regarding claim 11, Zhang wherein the transient BBB opening is achieved via administering ultrasound treatment and concomitantly administering microbubbles (p. 2 last paragraph).
Regarding claim 12, Zhang teaches wherein the tubulin inhibitor is abraxane (see above) and the abraxane is delivered to the glioblastoma at a concentration of at least about 0.3-0.5 μM (see Figure 3 D, ABX Brain concentration in μM, which reached approximately 0.4 μM).
Claims 1-4, 6 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over US PGPUB 20160319367 to Bernards (of record, cited on an IDS, hereinafter ‘Bernards’), as evidenced by Moudi (Moudi et al. Vinca Alkaloids. Int J Prev Med 2013;4:1231-5.).
Regarding claims 1 and 2, Bernards a method comprising:(a) detecting expression of signal sequence receptor 3 (SSR3) in a cancer sample from a subject, and administering a tubulin inhibitor such as a taxane to the subject if the expression of SSR3 is greater than a baseline:
[0006] The invention provides a method of typing a sample from a breast cancer patient that is treated with tamoxifen, the method comprising determining a level of expression for USP9X and/or for at least two genes that are selected from Table 1 in a relevant sample from the breast cancer patient, whereby the sample comprises expression products from a cancer cell of the patient; comparing said determined level of expression of USP9X or of the at least two genes to the level of expression of USP9X or the at least two genes in a reference; and typing said sample as being responsive to treatment with tamoxifen or not, based on the comparison of the determined levels of expression.
[0058] Furthermore, a Tamoxifen-Induced Gene Expression Signature (TIGES) was identified in USP9X knockdown cells that can be used to identify cancer patients, especially breast cancer patients, with a poor outcome after tamoxifen treatment. These genes, as indicated in Tables 1A and 1B, were identified as their relative level of expression was found to be modulated by the presence or absence of USP9X.
[0096] The present invention further provides a method of not assigning tamoxifen-comprising therapy to a breast cancer patient, comprising typing a sample from the breast cancer patient with a method according to the invention; and not assigning tamoxifen to a patient of which the sample is typed as being non-responsive to treatment with tamoxifen. Said method preferably comprises the assignment of further antiER directed therapy and/or chemotherapy to a breast cancer patient of which the sample is typed as being non-responsive to treatment with tamoxifen.
[0105] Said chemotherapy is preferably selected from a…taxane including paclitaxel and docetaxel…vincristine
Please note that SSR3 is listed in Table 1A in column 12 as one of the genes in the TIGES, used to identify cancer patients with poor outcome after tamoxifen treatment. In this case, it is upregulated, i.e., has expression greater than baseline
In summary, Bernards teaches measuring expression of a panel of genes in a cancer sample from a subject to identify tamoxifen-resistant breast cancer, wherein those genes include SSR3, and subsequently administering an alternative treatment, including tubulin inhibitors such as a taxane, to the subject if they are determined to be non-responsive to tamoxifen treatment.
Regarding claim 3, Bernards teaches wherein the cancer sample is obtained from a biopsy of a solid tumor from the subject (see above).
Regarding claim 4, Bernards teaches wherein the cancer is breast cancer (see above).
Regarding claim 6, Bernards teaches wherein the tubulin inhibitor is a taxane (see above).
Regarding claim 8, Bernards teaches wherein the tubulin inhibitor is vincristine. As evidenced by Moudi, vincristine is a vinca alkaloid (Abstract).
It would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have tried detecting expression of the genes in Bernards’ TIGES panel to identify a gene expression profile of tamoxifen-resistant breast cancer, including upregulated SSR3, and further to have tried administering a taxane to treat cancer identified as tamoxifen resistant. Bernards provides a teaching, suggestion or motivation to assay any two or more genes in the TIGES panel to identify tamoxifen-resistant breast cancer, providing a finite number of identified, predictable genes and their expression profiles to assay, a suggestion to try alternative treatments when tamoxifen is contraindicated, and a suggestion to try a finite number of identified, predictable, known effective alternative chemotherapeutic treatments, including taxanes, with a reasonable expectation of success.
Conclusion
No claims are allowed at this time.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMANDA M ZAHORIK whose telephone number is (703)756-1433. The examiner can normally be reached M-F 8:00-16:00 EST.
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/AMANDA M ZAHORIK/Examiner, Art Unit 1636
/BRIAN WHITEMAN/ Primary Examiner, Art Unit 1636
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