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 .
Information Disclosure Statement
1. The information disclosure statement (IDS) filed 02/24/2023 has been considered and the references therein are of record.
Claim Objections
2. Claim 9 is objected to because of the following informalities: contains a grammatical error, reciting, "instructions for of determining"; "of" should be deleted. Appropriate correction is required.
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.
3. Claims 2, 8, 10, and 15 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The term “at least about” in claims 2, 10, and 15 is a relative term which renders the claims indefinite. The term “at least about” 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. While the specification defines the relative term “about” (page 8, lines 12-20), the phrase “at least about” is not defined and renders the amount tHTT as indefinite.
Furthermore, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claims 2, 10, and 15 recite the broad recitation of "between about 0.01 ng/ml and about 1000 ng/ml", and the claim also recites "between about 1 ng/ml and about 100 ng/ml, between about 10 ng/ml and about 100 ng/ml, between about 100 ng/ml and about 1000 ng/ml, between about Ing/ml and about 10 ng/ml, between about 1 ng/ml and about 5 ng/ml, or between about 1.25 ng/ml and about 5 ng/ml" which are the narrower statements of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 8 recites the limitation "wherein step (c)" in referencing claim 6, which does not have a "step (c)". There is insufficient antecedent basis for this limitation in the claim.
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.
5. Claims 1-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. The claims recite the abstract idea of "determining the amount of wtHTT in the sample by determining a second amount of tHTT in the sample"; this is a mathematical calculation of subtracting the initial amount of tHTT from the second amount of tHTT. This judicial exception is not integrated into a practical application because the steps of removing mHTT from the sample to use the mathematical calculation of subtracting the initial amount of tHTT from the second amount of tHTT does not add meaningful limitation to the method as they are insignificant extra-solution activity. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because immunoprecipitation and pull-down assays to isolate and quantify the levels of a specific protein is a well-understood, routine, conventional laboratory activity in the field; simply appending well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception does not amount to significantly more than the judicial exception. See MPEP 2106.05(d) and 2106.07(a)III. Claims 2-8 are rejected under 35 U.S.C. 101 due to dependency on Claim 1. Claims 10-12 are rejected under 35 U.S.C. 101 due to dependency on Claim 9. Claims 15-20 are rejected under 35 U.S.C. 101 due to dependency on Claim 13.
6. Claims 13-20 rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. The claim(s) recite(s) the abstract idea of determining treatment for a subject based on comparing the amount of wtHTT in a sample to a reference value; it is a mental process to compare two values to determine a course of treatment. This judicial exception is not integrated into a practical application because the steps of determining the amount of wtHTT in a sample required to perform the mental process does not add a meaningful limitation to the method as they are insignificant extra-solution activity. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because comparing protein levels in a sample to a reference to determine the appropriate course of treatment is a well-understood, routine, conventional activity in the medical field; simply appending well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception does not amount to significantly more than the judicial exception. See MPEP 2106.05(d) and 2106.07(a)II. Claims 15-20 are rejected under 35 U.S.C. 101 due to dependency on Claim 13.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
7. Claims 1-6, 8-20 are rejected under 35 U.S.C. 103 as being unpatentable over Fodale et al., 2017 (see IDS Document No.4) in further view of Oskar et al., 2016 (WO 2016005545 A1) and Thermo Fisher, 2016 (instant PTO-892).
Instant claims 1-6, 8-20 are drawn towards a method of determining the amount of wild type huntingtin protein (wtHTT) in a sample by determining the difference between the total amount of huntingtin protein (tHTT) before and after removing mutant huntingtin protein (mHTT) using antibody-conjugated beads. This method is incorporated into a kit and into a method of determining treatment for a subject with Huntington’s disease based on wtHTT levels in the subject’s cerebral spinal fluid.
Fodale teaches a method of determining the first amount of tHTT in a sample using the 2B7 antibody conjugated to magnetic particles (page 351, 1st column, Immunoassay, 1st paragraph), wherein the 2B7 antibody binds to both wtHTT and mHTT (page 350, 1st column, Introduction, 2nd paragraph; page 351, 1st column, Antibodies and recombinant proteins, 1st paragraph), the first amount of tHTT is at least 15 fM (Fig 1B), and the sample is cerebral spinal fluid (page 350, 2nd column, Human CSF and blood samples, 1st paragraph) as required in claims 1-3, 9-11, 13-16. Fodale teaches contacting said sample with a mutant huntingtin protein (mHTT)-specific antibody composition that binds to the huntingtin protein captured on the magnetic particles (page 352, 2nd column, Immunoassay 1st paragraph), wherein the concentration of the mHTT-specific antibody is a function of the first amount of the tHTT (page 352, Fig. 1), and the concentration of the mHTT is between 16.5 fM and 10,000 fM (page 352, Fig. 1) as required in claims 1-2, 6, 9-10, 13-15, 19. Fodale teaches applying a magnetic field to the sample to remove the mHTT-specific antibody composition from the sample (page 351, 2nd column, Immunoassay 1st paragraph) as required by claims 1, 8-9, 13-14, 20.
Fodale does not explicitly teach determining the amount of wtHTT in the sample by determining a second amount of tHTT in the sample after the removal of mHTT as required by claims 1, 9, 13-14. While Fodale teaches monitoring mHTT levels in patients (page 350, 1st column, Introduction, 2nd paragraph), Fodale does not explicitly teach treating the subject with a treatment for Huntington's disease if the amount of wtHTT is decreased as compared to a reference value or continuing administering the treatment to the subject if the amount of wtHTT is unchanged or decreased as compared to a reference value as required in claims 13-14. While Fodale teaches a mHTT antibody composition that is fluorescently labeled using the Erenna kit from Singulex-Millipore (page 351-352, Results, Assay technology, antibodies, and detected signals, 1st paragraph; 1st column, Antibodies and recombinant proteins, 1st paragraph), Fodale does not explicitly teach the tHTT antibody being attached to a labeled secondary antibody or a kit for determining the amount of wtHTT in a sample that comprises a mHTT-specific antibody and a tHTT antibody as required by claims 4-5, 9, 11-12, 17-18. To summarize, Fodale does not explicitly teach all of the limitations of claims 1, 4-5, 9, 11-14, 17-18.
Oskar teaches “diagnosing Huntington's disease if the level of wt or mutated Huntingtin in said sample is changed in comparison to a reference sample” (page 78, claim 55), “monitoring the effect of Huntingtin lowering therapeutic strategies in pre-manifest or manifest Huntington's disease patient samples” (page 78, claim 55), “method to monitor the progress of Huntington's disease or to monitor the effectiveness of treatment of Huntington's disease in a mammal, comprising the steps of: determining the level of mutated HTT in a sample” (page 79, claim 63), and “determining the progress of Huntington's disease or the effectiveness of treatment of Huntington's disease by comparing the obtained level of mutated Huntingtin or fragments thereof with the levels obtained in the first measurement of mutated Huntingtin or fragments thereof, preferably in a measurement at the time of diagnosis of the disease associated symptoms, wherein a lowering of the HTT level is indicative of a successful therapy” (page 79, claim 63).
It would have been prima facie obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to arrive at the claimed invention from the disclosure of Fodale and Oskar. The method disclosed by Fodale isolates wtHTT by removing mHTT. Since wtHTT is inherently the amount of tHTT that is not mHTT, it would be obvious to a person having ordinary skill in the art to use the disclosed labeling Erenna kit to fluorescently label the 2B7 antibody and quantify tHTT before and after removing mHTT because Oskar teaches that wtHTT levels can be used to diagnose Huntington’s disease. One with ordinary skill in the art would be motivated to make and use the claimed invention because it is important to properly diagnose patients with Huntington’s disease. Further, it would be obvious to a person with ordinary skill in the art to simply substitute the monitoring of mHTT, as disclosed by Oskar, for monitoring wtHTT because determining the mHTT proportion of tHTT inherently determines the proportion of wtHTT and Oskar teaches that mHTT levels are useful for determining treatment for a patient with Huntington’s disease. It would also be obvious to a person with ordinary skill in the art to determine treatment if wtHTT is unchanged or decreased as compared to a reference because Oskar teaches that lowering mHTT is indicative of successful therapy and wtHTT is inherently the inverse since tHTT is a ratio of mHTT to wtHTT (lowering the proportion of mHTT means raising the proportion of wtHTT). One of ordinary skill in the art would have been motivated to measure wtHTT because it is important to correctly determine the course of treatment for a patient. Further, one would have found it obvious to combine the antibodies 2B7 and MW1 into a kit because a person with ordinary skill in the art would be motivated to make and use a kit of validated antibodies to determine wtHTT in a patient sample so they can appropriately diagnose a patient. The printed instructions in claim 9 do not hold patentable weight and are thus not limiting. The person of ordinary skill in the art would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references. Therefore, claims 1-6, 8-20 are obvious in view of the disclosures of Fodale and Oskar.
8. Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Fodale et al., 2017 (see IDS Document No.4) and Oskar et al., 2016 (WO 2016005545 A1) as applied to claims 1-6, 8-20, and in further view of Thermo Fisher, 2016 (instant PTO-892).
Claims 7 is drawn towards particles linked to the mHTT-specific antibody through antibody binding proteins, streptavidin-biotin interaction, or covalent immobilization.
Fodale and Oskar do not explicitly teach particles linked to the mHTT-specific antibody through antibody binding proteins, streptavidin-biotin interaction, or covalent immobilization.
Thermo Fisher teaches multiple equivalent methods of linking particles to antibodies, including through antibody binding proteins, streptavidin-biotin interaction, or covalent immobilization (Strategies for antibody immobilization, page 3-4).
It would have been prima facie obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to arrive at the claimed invention from the disclosure of Fodale and Oskar in view of Thermo Fisher. A person of ordinary skill in the art would have been motivated to make and use the invention as claimed because Thermo Fisher teaches these methods are good for linking antibodies to particles. The person of ordinary skill in the art would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references.
Conclusion
No claims are allowed.
Advisory Information
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/JOSEPH D. CESARE/ Examiner, Art Unit 1675
/JEFFREY STUCKER/ Supervisory Patent Examiner, Art Unit 1675