DETAILED ACTION
It is noted that this application has been transferred to Examiner Joseph G. Dauner of Art Unit 1682. Please direct all future correspondences to Examiner Dauner. Contact information for Examiner Dauner is provided at the end of this Office 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 .
The claims filed 3/12/2026 are under consideration.
Election/Restrictions
Applicant's election with traverse of the combination of SEQ ID NOs: 55, 67, 144, 161, 183 and 187, in the reply filed on 3/12/2026 is acknowledged.
The traversal is on the ground(s) that SEQ ID NOs: 1-484 are a group of patentably indistinct species because they correspond to the 242 miRNA sequences that are highly correlated with systemic lupus erythematosus (SLE). The traversal is further on the grounds that examination of all SEQ ID NOs: 1-484 does not place a serious search burden to the Office. This is not found persuasive because each of the SEQ ID NOs represent a mature or precursor sequence having a different sequence. Each sequence is distinct from one another and the search and consideration of one sequence is not informative to another sequence. For example, the consideration of hsa-miR-365a-3p, either by name or by sequence, does not provide information regarding hsa-let-7b-3p. The claims broadly encompass 484 different sequences for miRNAs and different combinations of at least one of the miRNAs. The genus of combinations represents a serious burden to the Office in terms of search and consideration.
The requirement is still deemed proper and is therefore made FINAL.
Priority
The present application is a continuation-in-part of PCT/JP2022/013311 (filed 3/22/2022), which claims benefit of 63/165,508 (filed 3/24/2021).
Priority is recognized.
Information Disclosure Statement
The listing of references in the specification or the citation of references throughout 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 or cited on a submitted IDS, they have not been considered.
Drawings
High resolution copies of the drawings may be accessed via PAIR/Patent Center Retrieval using the Supplemental Content tab.
The drawings are objected to because Figs. 3 and 5 characterize the “Top 10 up-regulated miRNAs” and the “Top 10 down-regulated miRNAs”. However, no miRNAs are specifically identified in the figures.
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.
Specification
The abstract of the disclosure is objected to because it exceeds the word limit. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
The disclosure is objected to because of the following informalities: Figs. 6-9 are described in paragraphs 222-225, respectively, as having color, i.e. “red” and “pink”. Also, paragraph 25, references color drawings. However, no color drawings have been provided. It is unclear if applicant intends the application to include color drawings because of the discrepancies between the drawings and the specification.
Appropriate correction is required.
Claim Objections
Claims 1 and 36 are objected to because of the following informalities: the claim lacks punctuation after the preamble in contrast with claim 4. Appropriate correction is required.
Claim 16 is objected to because of the following informalities: the claim recites “wherein as not having the marker…”. The language is grammatically incorrect. Appropriate correction is required.
Claim 21 is objected to because of the following informalities: the claim recites “regular polygonal, polygonal, hollow body”. The language is grammatically incorrect as the term “and”, “or” or “and/or” is missing between the last two elements of the list. Appropriate correction is required.
Claim Interpretation
In claim 1, the step of “determining the miRNA present in the sample” broadly encompassing determining miRNA present in any portion of the sample and is not limited to the captured or isolated extracellular vesicles from the sample.
Claim 19 recites the term “nm” in parentheses and is understood to be an abbreviation for “nanometers”.
Claim 36 recites the term (NSAIDs) in parentheses and is understood to be an abbreviation for “nonsteroidal anti-inflammatory drugs”.
Claim 37 recites the terms “PCR” and “NGS” in parentheses and are understood to be an abbreviation for “polymerase chain reaction” and “next generation RNA sequencing”, respectively.
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 4-36 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception without significantly more.
The claims are directed to the statutory category of a process.
The claim(s) recite(s):
“identifying the patient (i) as having the marker correlated with SLE if an increase in expression of at least one miRNA selected from SEQ ID NOs: 1-160 and 243-402 and/or a decrease in expression of at least one miRNA selected from SEQ ID NOs: 161-242 and 403-484 compared to a body fluid sample obtained from a healthy individual is detected in the patient sample” (claim 4);
“identifying the patient…(ii) as not having the marker correlated with SLE if an increase in expression of at least one miRNA selected from SEQ ID NOs: 1-160 and 243-402 and/or a decrease in expression of at least one miRNA selected from SEQ ID NOs: 161-242 and 403-484 compared to a body fluid sample obtained from a healthy individual fails to be detected” (claim 4);
“identifying the patient (i) as having the marker correlated with moderate SLE if a decrease in expression of at least one miRNA selected from SEQ ID NOs: 161-242 and 403-484 compared to a body fluid sample obtained from a healthy individual is detected in the patient sample” (claim 5);
“identifying the patient…(ii) as not having the marker correlated with moderate SLE if a decrease in expression of at least one miRNA selected from SEQ ID NOs: 161-242 and 403-484 compared to a body fluid sample obtained from a healthy individual fails to be detected” (claim 5);
“identifying the patient (i) as having the marker correlated with a comorbidity of SLE if an increase in expression of at least one miRNA selected from SEQ ID NOs: 1-160 and 243-402 and/or a decrease in expression of at least one miRNA selected from SEQ ID NOs: 161-242 and 403-484 compared to a body fluid sample obtained from a healthy individual is detected in the patient sample” (claim 6);
“identifying the patient…(ii) as not having the marker correlated with a comorbidity of SLE if an increase in expression of at least one miRNA selected from SEQ ID NOs: 1-160 and 243-402 and/or a decrease in expression of at least one miRNA selected from SEQ ID NOs: 161-242 and 403-484 compared to a body fluid sample obtained from a healthy individual fails to be detected” (claim 6);
“an increase in expression of at least one miRNA selected from SEQ ID NOs: 1-160 and 243-402 and/or a decrease in expression of at least one miRNA selected from SEQ ID NOs: 161-242 and 403-484 compared to a sample obtained from a healthy individual is detected in the patient sample is indicative of the patient having systemic lupus erythematosus (SLE)” (claim 15);
“wherein as not having the marker correlated with SLE if an increase in expression of at least one miRNA selected from SEQ ID NOs: 1-160 and 243- 402 and/or a decrease in expression of at least one miRNA selected from SEQ ID NOs: 161-242 and 403-484 compared to a body fluid sample obtained from a healthy individual fails to be detected” (claim 16); and
“the comorbidity is selected from the group consisting of cancer, a greater risk for cancer, cardiovascular, renal, liver, rheumatological disease, neurological diseases, hypothyroidism, psychosis, anaemia, and combinations thereof, if an increase in expression of at least one miRNA selected from SEQ ID NOs: 1-160 and 243-402 and/or a decrease in expression of at least one miRNA selected from SEQ ID NOs: 161-242 and 403-484” (claim 35).
The steps of “identifying” are abstract ideas in that they can be performed in a purely mental manner by considering the expression level of a single miRNA as compared to a reference. The concept of “comparing” further encompasses a mathematical concept.
The other elements identified above relate to the natural correlation between the expression levels of miRNA and SLE and its comorbidities.
The judicial exceptions are not integrated into a practical application because the claims do not involve:
improvements to the functioning of a computer or to any other technology or technical field;
applying or using the judicial exceptions to effect a particular treatment or prophylaxis for a disease or medical condition;
applying the judicial exception with, or by use of, a particular machine; or
effecting a transformation or reduction of a particular article to a different state or thing.
The claimed limitations add insignificant extra-solution activity to the judicial exceptions as they are data gathering steps. In addition to the judicial exception the claims recite steps of “detecting” miRNA in a sample. The claims further recite steps of using a nanowire to enrich for miRNA or extracellular vesicles comprising miRNA. These steps are not considered to integrate the judicial exception into a practical application because they merely add insignificant extra-solution activity (data gathering) to the judicial exception.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims encompass the use of commercially available arrays that are well-known and used in a conventional manner as described in paragraph 44 of the instant specification.
The teachings in the specification demonstrate the well understood, routine, conventional nature of the additional elements because it teaches that the additional elements are well known or commercially available. For example the specification teaches the following:
[0139] Detection of microRNAs can be performed using miRNA detection methods known to those skilled in the art, such as quantitative polymerase chain reaction (PCR), microarrays for miRNA detection, RNA-Seq, (e.g., next generation sequencing (NGS)), and multiplex miRNA profiling, and the like.
The prior art also demonstrates the well understood, routine, conventional nature of additional elements because it teaches that the additional elements are well known or commercially available. For example, Yasui (Sci Adv 2017; 3 e1701133) and Takeshita (MicroTAS 2015 - 19th International Conference on Miniaturized Systems for Chemistry and Life Sciences. Chemical and Biological Microsystems Society, 10/2015. p. 1516-1518) teach methods of using a nanowire to enrich for miRNA or extracellular vesicles comprising miRNA.
Further it is noted that the courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity:
Determining the level of a biomarker in blood by any means, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017);
Using polymerase chain reaction to amplify and detect DNA, Genetic Techs. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016); Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1377, 115 USPQ2d 1152, 1157 (Fed. Cir. 2015);
Detecting DNA or enzymes in a sample, Sequenom, 788 F.3d at 1377-78, 115 USPQ2d at 1157); Cleveland Clinic Foundation 859 F.3d at 1362, 123 USPQ2d at 1088 (Fed. Cir. 2017).
For the reasons set forth above the claims are not directed to patent eligible subject matter.
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 4-37 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.
Regarding claim 4, the claim is incomplete as the miRNA levels required in the identifying step are not analyzed in the step of “analyzing miRNA expression in the obtained sample”.
Claims 5-36 are rejected as they depend from claim 4.
Regarding claim 5, it is unclear if step (c) of claim 5 is intended to further limit step (c) of claim 4, replaces step (c) of claim 4 or is required in addition to step (c) of claim 4.
Regarding claim 6, it is unclear if step (c) of claim 6 is intended to further limit step (c) of claim 4, replaces step (c) of claim 4 or is required in addition to step (c) of claim 4.
Regarding claim 8, the claim recites “the obtained body fluid sample”, which lacks proper antecedent basis.
Regarding claim 13, the claim recites “the extracellular vesicle”, which lacks proper antecedent basis.
Regarding claims 17, 18, 19, 20, 21, 22, 23, 24 and 25, the claims recite “the nanowire”, which lacks proper antecedent basis.
Regarding claims 21-23, the claims recite the term “substantially” in describing a claim element. It is unclear what the metes and bounds of those elements are. For example, it is unclear when a shape is sufficient to be “cylindrical” and when it is not sufficient to be “substantially cylindrical”.
Regarding claims 26, 27, 29 , the claim recites “the extracellular vesicles”, which lacks proper antecedent basis.
Regarding claim 28, the claim recites “extracting miRNA”, which lacks proper antecedent basis.
Regarding claim 28, the claim recites “the device”, which lacks proper antecedent basis.
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.
Claims 15 and 16 are 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 15 recites an intended use or result of the method of claim 4. The claim does not require any additional active method steps nor does it limit any of the elements of claim 4. Thus, claim 15 fails to further limit the scope of the method of claim 4.
Claim 16 recites an intended use or result of the method of claim 4. The claim does not require any additional active method steps nor does it limit any of the elements of claim 4. Thus, claim 16 fails to further limit the scope of the method of claim 4.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 (i.e., changing from AIA to pre-AIA ) 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.
(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.
Claim(s) 1, 2, 4, 5, 6, 8, 10, 11, 12, 13, 14, 15, 16, 26, 29, 34 and 35 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by CN 105441578 B (hereafter ‘578; citations to translation from Google Patents).
The following rejections are over an unelected embodiment.
Regarding claims 1 and 2, ‘578 teaches obtaining a urine sample (p. 3, 1. Processing of urine samples).
‘578 teaches isolating extracellular vesicles by extracting exosomes (p. 3, 2. Extraction of exosome).
‘578 teaches disrupting the exosomes in order to extract exosome total RNA (p. 3, 3 Extraction of exosome total RNA).
‘578 teaches detecting miRNA present in the exosomes of the sample, including hsa-miR-1207-5p (p. 4, Data Analysis). SEQ ID NO: 2 of ‘578 is identical to SEQ ID NO: 8 of the present application.
Regarding claims 4, 11, 12 and 29, ‘578 teaches obtaining a urine sample from a patient with SLE as broadly encompassed by a “patient suspected of having SLE” (p. 3, 1. Processing of urine samples).
‘578 teaches analyzing miRNA present in the sample, including hsa-miR-1207-5p (p. 4, Data Analysis). SEQ ID NO: 2 of ‘578 is identical to SEQ ID NO: 8 of the present application.
‘578 teaches identifying the patient as having a marker correlated with SLE involving active lupus nephritis when hsa-miR-1207-5p is increased relative to healthy patients (p. 4).
Regarding claim 5, ‘578 teaches identifying the patient as having a marker correlated with SLE involving active lupus nephritis when hsa-miR-1207-5p is increased relative to healthy patients (p. 4).
The above teachings of ‘578 are broadly encompassed by option (c)(ii) of claim 5.
Regarding claims 6, 34 and 35, ‘578 teaches identifying the patient as having a marker correlated with SLE involving active lupus nephritis as a comorbidity when hsa-miR-1207-5p is increased relative to healthy patients (p. 4).
The above teachings of ‘578 are broadly encompassed by option (c)(i) of claim 6.
Regarding claims 8 and 10, ‘578 teaches extracting extracellular vesicles by extracting exosomes from urine (p. 3, 2. Extraction of exosome).
‘578 teaches analyzing the oligonucleotide sequences of RNA extracted from the exosomes by converting RNA to cDNA (forming a “cDNA library”) and running real-time fluorescent quantitative PCR reactions to generate an miRNA expression profile for hsa-miR-1202 and hsa-miR-1207-5p using the cDNA library (p. 3-4).
Regarding claim 13, ‘578 teaches extracting extracellular vesicles by extracting exosomes from urine (p. 3, 2. Extraction of exosome).
Regarding claim 14, ‘578 teaches isolating exosomes using differential ultracentrifugation/density gradient centrifugation (p. 3, 2. Extraction of exosomes).
Regarding claim 15, the claim does not further limit any element of claim 4, nor does it require any additional active method steps. The claim merely sets forth information useful to using miRNA expression levels. ‘578 anticipates claim 15 for the same reason as claim 4.
It is also noted that ‘578 teaches identifying increased hsa-miR-1207-5p relative to healthy patients, which is indicative of SLE with active lupus nephritis (p. 4).
Regarding claim 16, the claim does not further limit any element of claim 4, nor does it require any additional active method steps. The claim merely sets forth information useful to using miRNA expression levels. ‘578 anticipates claim 16 for the same reason as claim 4.
It is also noted that ‘578 teaches identifying increased hsa-miR-1207-5p relative to healthy patients, which is indicative of SLE with the comorbidity active lupus nephritis (p. 4).
Regarding claim 26, ‘578 teaches exosomes are disrupted by a cytolysis buffer that is part of the mirVana PARIS mirVana Protein And RNA lsolation System (p. 3, 3 Extraction of exosome total RNA).
Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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 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:
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.
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.
Claim(s) 3, 7, 9, 17, 18, 19, 20, 21, 22, 23, 24, 25, 28, 30, 31, 32, 33 and 37 is/are rejected under 35 U.S.C. 103 as being unpatentable over CN 105441578 B (hereafter ‘578; citations to translation from Google Patents) in view of Yasui (US 2020/0164375 A1).
The following rejections are over an unelected embodiment.
Regarding claims 3, 7, 9, 30, 37, ‘578 teaches obtaining a urine sample (p. 3, 1. Processing of urine samples) from a patient with SLE as broadly encompassed by a “patient suspected of having SLE” (p. 3, 1. Processing of urine samples).
‘578 teaches isolating extracellular vesicles by extracting exosomes (p. 3, 2. Extraction of exosome).
‘578 teaches disrupting the exosomes in order to extract exosome total RNA (p. 3, 3 Extraction of exosome total RNA).
‘578 teaches detecting and analyzing miRNA present in the exosomes of the sample, including hsa-miR-1207-5p (p. 4, Data Analysis). SEQ ID NO: 2 of ‘578 is identical to SEQ ID NO: 8 of the present application.
‘578 teaches identifying the patient has having a marker correlated with SLE involving active lupus nephritis when hsa-miR-1207-5p is increased relative to healthy patients (p. 4).
While ‘578 teaches the above methods, it does not teach the use of a device with a nanowire (claims 3 and 7), or the additional elements specific to claims 9, 17, 18, 19, 20, 21, 22, 23, 24, 25, 28, 30, 31, 32, 33 and 37.
However, Yasui teaches a device used to separate biomolecules, including microvesicles.
Regarding claims 3 and 9, Yasui teaches a device comprising a nanowire that at is used to isolate extracellular microvesicles, such as exosomes (para. 6, 56 and 58).
Regarding claims 7, 9, 30 and 37, Yasui teaches the device is used by introducing a sample into the fluidic device comprising the nanowire (para. 159), capturing the extracellular vesicles on the nanowire (para. 159) and extracting nucleic acids from the capture extracellular vesicles (para. 165), which would be disrupted to release the nucleic acids.
Yasui further teaches analyzing nucleic acids obtained with a DNA sequencer or an RNA sequencer (para. 165).
Regarding claim 17, Yasui teaches the nanowires are made of a variety of materials, including ZnO (para. 100).
Regarding claim 18, Yasui teaches the nanowires are made of Mn2O3, NiO or CuO (para. 100), which are magnetic.
Regarding claims 19 and 20, Yasui teaches the nanowire has length of 5 to 50 nanometers (para. 94).
Regarding claim 21, Yasui teaches the cross-section of the nanowire is a regular polygonal (para. 95).
Regarding claim 22, Yasui teaches the outer shape of the nanowires may be substantially cylindrical, elliptical or polygonal (para. 95).
Regarding claim 23, Yasui teaches the nanowires may be hollow or hollow bodies or may be substantially material-packed structures (para. 95).
Regarding claim 24, Yasui teaches the nanowire may be formed of one material or a plurality of materials (para. 96).
Regarding claim 25, Yasui teaches the nanowire may be coated on its surface with a coating material (para. 96).
Regarding claim 28, Yasui teaches the use of a device comprising a nanowire to extract nucleic acids, such as miRNA, as described above. This is broadly encompassed by the claimed element that “extracting miRNAs is performed in situ” in view of the instant specification.
Regarding claims 31 and 32, Yasui teaches the device has a plurality of wells in the form of fluid chambers (para. 83), to which nanowires are attached (para. 90).
Regarding claim 33, Yasui teaches the device includes a cover (para. 6, 8).
It would have been prima facie obvious to the ordinary artisan at the time of filing to have modified the method of ‘578 by replacing the centrifugal based isolation of microvesicles with the use of the device of Yasui. One would have been motivated to do so because the device of Yasui can use a small sample volume that is sufficient to separate and detect RNA to identify a disease or disorder and the sample volume can yield an improved collection of less than or less than a volume such as 1 ml, 500 μl, 300 μl, 250 μl, 200 μl, 150 μl, 100 μl, 50 μl, 30μl, 20 μl or 10 μl, as opposed to 1 to 20 ml required for centrifugation separation (para. 178 of Yasui). The modification has a reasonable expectation of success as it simply replaces one known technique for isolating microvesicles for another known technique for isolating microvesicles.
Claim(s) 27 is/are rejected under 35 U.S.C. 103 as being unpatentable over CN 105441578 B (hereafter ‘578; citations to translation from Google Patents) in view of Moldovan (J Cell Mol Med. 2014. 18(3):371-390).
Regarding claim 27, ‘578 teaches obtaining a urine sample from a patient with SLE as broadly encompassed by a “patient suspected of having SLE” (p. 3, 1. Processing of urine samples).
‘578 teaches analyzing miRNA present the sample, including hsa-miR-1207-5p (p. 4, Data Analysis). SEQ ID NO: 2 of ‘578 is identical to SEQ ID NO: 8 of the present application.
‘578 teaches identifying the patient has having a marker correlated with SLE involving active lupus nephritis when hsa-miR-1207-5p is increased relative to healthy patients (p. 4).
‘578 teaches exosomes are disrupted by a cytolysis buffer that is part of the mirVana PARIS mirVana Protein And RNA lsolation System (p. 3, 3 Extraction of exosome total RNA).
‘578 does not teach the additional elements specific to claim 27.
However, Moldovan teaches that it was known that the mirVana PARIS system uses a non-ionic detergent to disrupt samples (p. 379, Silica-based miRNA recovery methods).
Thus, it would have been obvious that in using the mirVana PARIS system, the extracellular vesicles of ‘578 would have been disrupted by a detergent pre-treatment.
Claim(s) 36 is/are rejected under 35 U.S.C. 103 as being unpatentable over CN 105441578 B (hereafter ‘578; citations to translation from Google Patents) in view of Elmore (WO 2012/071374 A1).
Regarding claim 36, ‘578 teaches obtaining a urine sample from a patient with SLE as broadly encompassed by a “patient suspected of having SLE” (p. 3, 1. Processing of urine samples).
‘578 teaches analyzing miRNA present the sample, including hsa-miR-1207-5p (p. 4, Data Analysis). SEQ ID NO: 2 of ‘578 is identical to SEQ ID NO: 8 of the present application.
‘578 teaches identifying the patient has having a marker correlated with SLE involving active lupus nephritis when hsa-miR-1207-5p is increased relative to healthy patients (p. 4).
While ‘578 teaches treating patients, the reference is silent regarding the specific treatments of claim 36.
However, Elmore demonstrates that it was known that NSAIDs are used to treat SLE and lupus nephritis (p. 41).
It would have been prima facie obvious to the ordinary artisan at the time of filing to have treated the patients of ‘578 with any known treatment for SLE and lupus nephritis, including NSAIDs.
Improper Markush Group
Claims 4-37 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984).
A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 706.03(y).
The claims recite the following Markush grouping: at least one miRNA selected from the group consisting of SEQ ID NOs: 1-484. The Markush group is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
It is first noted that MPEP 706.03(y) states that “A Markush claim may be rejected under judicially approved “improper Markush grouping” principles when the claim contains an improper grouping of alternatively useable members. A Markush claim contains an “improper Markush grouping” if either: (1) the members of the Markush group do not share a “single structural similarity” or (2) the members do not share a common use. Supplementary Guidelines at 7166 (citing In re Harnisch, 631 F.2d 716, 721-22, 206 USPQ 300, 305 (CCPA 1980)). “ Members of a Markush group share a “single structural similarity” when they belong to the same recognized physical or chemical class or to the same art-recognized class (prong 1) and the members of a Markush group share a common function or use when they are disclosed in the specification or known in the art to be functionally equivalent (prong 2).
The phrase “significant structural element is shared by all of the alternatives” refers to cases where the compounds share a common chemical structure which occupies a large portion of their structures, or in case the compounds have in common only a small portion of their structures, the commonly shared structure constitutes a structurally distinctive portion in view of existing prior art, and the common structure is essential to the common property or activity.
A recognized physical class, a recognized chemical class, or an art-recognized class is a class wherein “there is an expectation from the knowledge in the art that members of the class will behave in the same way in the context of the claimed invention. In other words, each member could be substituted one for the other, with the expectation that the same intended result would be achieved” (see MPEP 706.03(y)IIA).
Herein, the recited alternative species do not share a single structural similarity, as each miRNA has a different chemical structure in that it consists of a different nucleotide sequence. The only structural similarity present is that all of the miRNA comprise nucleotides. The fact that the miRNA comprise nucleotides per se does not support a conclusion that they have a common single structural similarity because the structure of comprising nucleotides alone is not essential to the asserted common activity of being correlated with lung cancer. Accordingly, while the different miRNA are asserted to have the property of being correlated with lung cancer, they do not share a substantial structural similarity essential to this activity.
Further, the recited miRNA do not belong to a chemical or art-recognized class because there is no expectation from the knowledge in the prior art that miRNA behave in the same manner and can be substituted for one another with the same intended result achieved. There is no evidence of record to establish that it is clear from their very nature that the recited miRNA possess the common property of being correlated with lung cancer.
Following this analysis, the claims are rejected as containing an improper Markush grouping.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Conclusion
No claims allowed.
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/JOSEPH G. DAUNER/Primary Examiner, Art Unit 1682
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