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 .
Claims 1-10 are pending and are being examined on the merits.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claim Objections
Claims 1-8 are objected to because of the following informalities:
In claim 1, the limitation “a disease risk thereof” in l. 2 should be “a risk thereof”.
Further, for clarity, the Examiner suggests amending (2) to read: “(2) a primer or a primer pair, or a probe that is specific to an RPN11 mRNA or an RPN11 cDNA, or a chip comprising the primer, primer pair or probe”.
In claim 2, the limitation “wherein the detection reagent comprises” in ll. 1-2 should be “wherein the detection reagent further comprises”.
In claim 3, the Examiner suggests amending the “wherein” clause to read “wherein the detection reagent further comprises a primer or a primer pair, or a probe that is specific to an MMSET mRNA or an MMSET cDNA, or a chip comprising the primer, primer pair or probe”.
In claim 4, the limitation “a disease risk thereof” in l. 1 should be “a risk thereof”.
Further, the limitation “kit comprises at least one selected from the group” in ll. 3-4, should be “kit comprises at least one component selected from the group”. Finally, the limitation “an RPN11 detection gene” in l. 4 should be “an RPN11 gene”, and the limitation “an RPN11 expression protein” in l. 5 should be “an RPN11 protein”.
In claim 5, the limitation “kit comprises at least one selected from the group” in ll. 1-2, should be “kit further comprises at least one component selected from the group”. Further, the limitation “an MMSET expression protein” in l. 3 should be “an MMSET protein”.
In claim 6, the limitation “kit further comprises at least one selected from the group” in ll. 1-2, should be “kit further comprises at least one component selected from the group”. Further, the limitation “an RPN11 expression protein” in l. 3 should be “an RPN11 protein”.
In claim 7, the limitation “kit further comprises at least one selected from the group” in ll. 1-2, should be “kit further comprises at least one component selected from the group”. Further, the limitation “an MMSET expression protein” in l. 3 should be “an MMSET protein”.
In claim 8, “administrating” in l. 3 should be “administering”.
Appropriate correction is required.
Claim Interpretation
In claim 1, the preamble recites “for detecting of … SMM and … MM and a … risk thereof, molecular typing of an MM patient, prognostic analysis of the MM patient, and prediction of a response of the MM patient to bortezomib treatment …”, which is a statement of intended use. Since the body of the claim recites a structurally complete invention, the statement of intended use in the preamble is not considered a claim limitation. See MPEP 2111.02 (II). The claim 4 preamble is construed in the same manner.
In claim 2, the limitation “MM Suppressor of variegation, Enhancer of zeste, and Trithoraz (MMSET)” is being interpreted as it is described in the instant specification (para. 5) and in accordance with its meaning in the art, e.g., as described in Hudlebusch (abstract; cited below in conjunction with the prior art rejections) …
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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 1-7 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more.
Eligibility is considered in light of MPEP 2106 III, which incorporates the 2019 Revised Patent Subject Matter Eligibility Guidance (2019 PEG) published on January 17, 2019 (84 Fed. Reg. 50) and is clarified in the October 2019 Update.
As can be seen in the MPEP 2106 III Figure, eligibility analysis requires one to address the following questions: (i) Step 1 – Is the claim directed to one of the four statutory categories (i.e., process, machine, manufacture or composition of matter); (ii) Step 2A – Is the claim directed to a judicial exception (i.e., a natural phenomenon, law of nature or abstract idea); and (iii) Step 2B – does the claim recite additional elements that amount to significantly more than the judicial exception. In addition, as can be seen in the MPEP 2106.04 II Figure, Step 2A is a two-prong inquiry, with Prong One asking whether the claims recite a judicial exception (i.e., an abstract idea, natural phenomenon or law of nature) and Prong Two asking whether the claims recite additional elements that integrate the judicial exception into a practical application.
In this case, as to Step 1, claims 1-7 are directed to one of the four statutory categories since they are drawn to a composition of matter.
The analysis cannot be streamlined, so the claims are considered with respect to Step 2A.
With respect to Prong One of Step 2A, claims 1-7 recite a judicial exception. Specifically, the primers and probes1 are a product of nature (i.e., a natural phenomenon), as noted in the instant specification (paras. 5, 7-8 - since the target sequences are a product of nature, primers/probes specific to those target sequences are also a product of nature).
With respect to Prong Two of Step 2A, the claims do not recite additional elements that integrate the judicial exceptions into a practical application for the following reason. In particular, claims 1-7 do not require any components other than the judicial exceptions. In addition, to the extent that “kit” in the preamble of claims 4-7 is construed to require something additional, such as assembling the various oligonucleotides into container(s), this constitutes insignificant extra-solution activity as described in the 2019 PEG and MPEP 2106.05(g).
Thus, the answer to step 2A is “Yes, the claims are directed to a judicial exception,” and the analysis moves to Step 2B, which asks if the additional elements in the claim amount to significantly more than the judicial exception.
In this case, claims 1-7 do not include additional elements that are sufficient to amount to significantly more than the judicial exception because only routine and conventional elements are recited in combination with the judicial exceptions. That is, the only limitation that could be construed to be an additional element is “kit”, and assembling oligonucleotides into kits was performed routinely prior to the effective filing date of the claimed invention (e.g., see Burczynski; para. 27; cited below in conjunction with the prior art rejections). Therefore, the additional element, to the extent that there is one, in claims 1-7 is not non-routine or unconventional.
In view of the foregoing, claims 1-7 are rejected under 35 U.S.C. 101 as being drawn to a judicial exception without significantly more.
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 1-3 and 8-11 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.
Claim 1 recites the limitation “an RPN11-specific binding molecule”, the meaning of
which is unclear. The specification uses the term “RPN11” to refer both to a protein and to its corresponding nucleic acid sequence (para. 7). Elsewhere in the claims, e.g., claim 4, it is further specified whether “RPN11” is referring to a nucleic acid (gene, mRNA or cDNA) or a protein. However, in this limitation in claim 1, such a distinction is not made. Since a nucleic acid, perhaps, a primer, can specifically bind to an RPN11 nucleic acid, perhaps, a genomic sequence, and since a protein, perhaps, an antibody, can specifically bind to an RPN11 protein, it is not clear if the “RPN11-specific binding molecule” in claim 1 is referring to a nucleic acid binding molecule or a protein binding molecule. Since the ordinary artisan would not be able to determine the metes and bounds of the claim, it is indefinite. Claim 2 similarly recites a “MMSET-specific binding molecule”, and is rejected with corresponding reasoning.
Claims 2-3 depend from claim 1 and consequently incorporate the indefiniteness issues of claim 1.
The term “high” in claim 8 is a relative term which renders the claim indefinite. The term “high” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Specifically, it is not clear what minimum level of RPN11 expression would be considered “high”. Since the ordinary artisan would not be able to determine the metes and bounds of the claim, it is indefinite.
Claims 9-10 depend from claim 8 and consequently incorporate the indefiniteness issues of claim 8.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 6 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 6 recites the limitation “the kit further comprises at least one selected from the
group consisting of an RPN11 gene, and RPN11 mRNA, and RPN11 cDNA, and an RPN11 expression protein” and further recites “to serve as a reference substance or a quality control”. Claim 6 depends from claim 4, which also recites the “at least one selected from the group consisting of [the 4 recited molecules]” limitation. The additional limitation “to serve as …” in claim 6 is a statement of intended use. Since the intended use does not impose any additional structural limitations on the claim 4 kit, it does not further limit the claim 4 kit. Consequently, claim 6 is in improper dependent form.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Duplicate Claim Warning
Applicant is advised that should claim 5 be found allowable, claim 7 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claims 5 and 7 each depend from claim 4 and each recite “the kit [further] comprises at
least one selected from the group consisting of an MMSET gene, and MMSET mRNA, and MMSET cDNA, and an MMSET expression protein”. Claim 7 additionally recites the limitation “to serve as …”, which is a statement of intended use. Since the intended use does not impose any additional structural limitations on the claim 4 kit, the scope of claim 7 is the same as claim 5. Thus, claims 5 and 7 are substantial duplicates.
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.
Claims 1, 4 and 6 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Burczynski (US Patent App. Pub. No. 2008/0280774 A1), as evidenced by Song (Blockade of deubiquitylating enzyme Rpn11 triggers apoptosis in multiple myeloma cells and overcomes bortezomib resistance, Oncogene, 36, 5631-5628, 2017).
Regarding independent claim 1, Burczynski teaches …
A detection reagent for detection of smoldering multiple myeloma (SMM) and multiple myeloma (MM) and a disease risk thereof, molecular typing of an MM patient, prognostic analysis of the MM patient, and prediction of a response of the MM patient to bortezomib treatment, comprising the following components: (1) an RPN11-specific binding molecule and/or an RPN11-specific antibody; and (2) a primer or a primer pair, a probe, or a chip that specifically amplifies an RPN11 mRNA or an RPN11 cDNA. Specifically, Burczynski teaches a kit comprising reagents including target-specific binding molecules, specifically, target-specific antibodies, plus target-specific nucleic acid primers, hybridization probes or arrays for detecting cancer biomarkers (paras. 23-24, 27-28, 127, 129-131, 139, 141, 168-170; claims 39, 43-44). Burczynski additionally teaches that the target is POH1 (Table 7, p. 27), which is a synonym for RPN11, as evidenced by Song (abstract).
Regarding independent claim 4 and dependent claim 6, Burczynski teaches …
A detection kit for detection of SMM and MM and a disease risk thereof, molecular typing of an MM patient, prognostic analysis of the MM patient, and prediction of a response of the MM patient to a bortezomib treatment, wherein the kit comprises at least one selected from the group consisting of an RPN11 detection gene, an RPN11 mRNA, an RPN11 cDNA, and an RPN11 expression protein. Specifically, Burczynski teaches a kit comprising reagents including target-specific binding molecules, specifically, target-specific antibodies, plus target-specific nucleic acid primers, hybridization probes or arrays for detecting cancer biomarkers, and teaches a target gene sequence and transcript for use as a control (paras. 23-24, 27-28, 106, 127, 129-131, 139, 141, 168-170, 172, 181; claims 39, 43-44, 59, 61). Burczynski additionally teaches that the target is POH1 (Table 7, p. 27), which is a synonym for RPN11, as evidenced by Song (abstract).
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.
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 2-3, 5 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Burczynski (US Patent App. Pub. No. 2008/0280774 A1), as evidenced by Song (Blockade of deubiquitylating enzyme Rpn11 triggers apoptosis in multiple myeloma cells and overcomes bortezomib resistance, Oncogene, 36, 5631-5628, 2017), as applied to claims 1 and 4 above, and further in view of Hudlebusch (The Histone Methyltransferase and Putative Oncoprotein MMSET Is Overexpressed in a Large Variety of Human Tumors, Clin. Cancer Res., 17(9): 2912-2933, 2011).
Regarding dependent claims 2-3, as noted above, Burczynski teaches various target-specific oligonucleotides and corresponding arrays, and antibodies/binding molecules (paras. 23-24, 27-28, 106, 127, 129-131, 139, 141, 168-170, 172, 181; claims 39, 43-44, 59, 61). Further, Hudlebusch teaches MMSET being deregulated in multiple myeloma patients, as well as patients with other kinds of cancers, e.g., leukemias, and teaches that it is a potential biomarker for multiple myeloma and other cancers (e.g., abstract; p. 2920, right col., para. 1).
Prior to the effective filing date of the instant invention, it would have been prima facie obvious to modify the Burczynski method and corresponding reagent kit to incorporate MMSET as a biomarker into the method, and to include corresponding MMSET reagents into the reagent kit. Burczynski teaches kits and methods for detecting and measuring biomarkers for leukemia (e.g., abstract). Hudlebusch teaches that MMSET is a potential biomarker for leukemia. The ordinary artisan would have been motivated to add the MMSET biomarker into the RPN11 biomarker detection method, and the MMSET reagents into the biomarker kit, with the expectation that doing so would result in the advantage of providing additional information about the etiology or pathology of that particular patient’s cancer. The ordinary artisan would have had an expectation of success as the design and modification of biomarker assays is well-known in the art, and because Burczynski teaches that the method can comprise multiple biomarkers (paras. 11, 20, 40, 143; claim 22).
Regarding dependent claims 5 and 7, Burczynski teaches various target-specific oligonucleotides and corresponding arrays, and antibodies/binding molecules, and teaches a target gene sequence and transcript for use as a control (paras. 23-24, 27-28, 106, 127, 129-131, 139, 141, 168-170, 172, 181; claims 39, 43-44, 59, 61). Further, Hudlebusch teaches MMSET being deregulated in multiple myeloma patients, as well as patients with other kinds of cancers, e.g., leukemias, and teaches that it is a potential biomarker for multiple myeloma and other cancers (e.g., abstract; p. 2920, right col., para. 1).
Prior to the effective filing date of the instant invention, it would have been prima facie obvious to modify the Burczynski method and corresponding reagent kit to incorporate MMSET as a biomarker into the method, and to include corresponding MMSET reagents into the reagent kit. Burczynski teaches kits and methods for detecting and measuring biomarkers for leukemia (e.g., abstract). Hudlebusch teaches that MMSET is a potential biomarker for leukemia. The ordinary artisan would have been motivated to add the MMSET biomarker into the RPN11 biomarker detection method, and the MMSET reagents into the biomarker kit, with the expectation that doing so would result in the advantage of providing additional information about the etiology or pathology of that particular patient’s cancer. The ordinary artisan would have had an expectation of success as the design and modification of biomarker assays is well-known in the art, and because Burczynski teaches that the method can comprise multiple biomarkers (paras. 11, 20, 40, 143; claim 22).
Li (Capzimin is a potent and specific inhibitor of proteasome isopeptidase Rpn11, Nature Chemical Biology, 13, 486-493, 2017) in view of Sato (Clinical and prognostic significance of t(4;14) translocation in multiple myeloma in the era of novel agents, International Journal of Hematology, 113, 207-213, 2020).
Regarding independent claim 8 and dependent claims 9-10, as noted above the term “high” in claim 8 is indefinite. However, Li teaches …
A method for treating MM with a RPN11 expression level in a subject in need thereof, comprising administering an effective amount of RPN11 inhibitor, optionally a small-molecule inhibitor, optionally Capzimin, to the subject (e.g., abstract)
Further, Sato teaches that the t(4;14) translocation is associated with multiple myeloma and MMSET, as well as with a poor prognosis and drug resistance (p. 207, left col., para. 1; p. 211, right col., para. 2 through p. 212, left col., para. 1).
Prior to the effective filing date of the instant invention, it would have been prima facie obvious to modify the Li method to incorporate the t(4;14) translocation as a biomarker into the method. Li teaches methods for detecting and measuring biomarkers for multiple myeloma. Sato teaches that the t(4;14) translocation is a biomarker for multiple myeloma. The ordinary artisan would have been motivated to add the t(4;14) translocation biomarker into the RPN11 biomarker detection method with the expectation that doing so would result in the advantage of providing additional information about the etiology or pathology of that particular patient’s cancer. The ordinary artisan would have had an expectation of success as the design and modification of biomarker assays is well-known in the art.
Conclusion
Claims 1-10 are being examined and are rejected. Claims 1-8 are objected to. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CAROLYN GREENE whose telephone number is (571)272-3240. The examiner can normally be reached M-Th 7:30-5:30 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gary Benzion can be reached at 571-272-0782. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CAROLYN L GREENE/Primary Examiner, Art Unit 1681
1 As noted in the 35 USC § 112(b) rejections below, it is not clear that the “RPN-specific binding molecule” in claim 1 is a nucleic acid or a protein.
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