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 .
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.821 - 1.825 because it does not contain a "Sequence Listing" as a separate part of the disclosure or a CRF of the “Sequence Listing.”.
Required response - Applicant must provide:
A "Sequence Listing" part of the disclosure; together with
An amendment specifically directing its entry into the application in accordance with 37 CFR 1.825(a)(2);
A statement that the "Sequence Listing" includes no new matter as required by 37 CFR 1.821(a)(4); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(a)(3).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
If the "Sequence Listing" part of the disclosure is submitted according to item 1) c) or d) above, applicant must also provide:
A CRF in accordance with 37 CFR 1.821(e)(1) or 1.821(e)(2) as required by 1.825(a)(5); and
A statement according to item 2) a) or b) above.
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.821 - 1.825 because the application does not contain a statement that the CRF is identical to the "Sequence Listing" part of the disclosure, as described above in item 1), as required by 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii).
Required response - Applicant must provide such statement.
DETAILED ACTION
Status of Application/Election/Restrictions
3. Claims 1-31 are pending in this Application and under examination in this office action.
Specification
4. The disclosure is objected to because of the following informalities: The use of the term “SiMoA” (p. 38, [00149]; p. 40, [00158]; p. 47, [00176]; p. 48, [00177]) “Quanterix” (p. 39, [00153], which is a trade name or a mark used in commerce, has been noted in this application. The term 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. Appropriate correction is required.
Claim Objection
5. Claim 1,6, 7, 9-10, 19-20, and 27 are objected to because of the following informalities: The limitations “p217+tau” and “NFL” are not unique or common abbreviations in the art. Applicants are required to spell out “p217+tau” and “NFL” at the first usage. Appropriate correction is required.
Claim Rejections - 35 USC § 112
6. 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 1-31 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 pre-AIA the applicant regards as the invention.
Claims 1-31 are indefinite because:
i. The limitation “p217+Tau” recited in independent claims 1, 9-10, 19-20, and 27, and the limitations “amino acids 210-220” in claim 4 and “amino acids 7-20 or 116-127” in claim 5 are indefinite because human tau protein has different isoforms and it is unclear to which specific isoform sequence and corresponding positions are referred.
ii. Regarding claim 27, it is unclear what other members within the limitation “…selected from a group comprising NFL, adiponectin and leptin”. The limitation “…selected from a group comprising NFL, adiponectin and leptin” is not limited to recited NFL, adiponectin and leptin but also encompasses other undefined members within the recited Markush group. The metes and bounds of what is encompassed within the recited Markush group cannot be determined, which renders the claim indefinite.
iii. Claims 27-31 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential elements, such omission amounting to a gap between the elements/steps. See MPEP § 2172.01. The omitted elements are: how to determine or predict whether the subject has tauopathy is at risk of developing tauopathy without specific parameters based on comparison of undefined reference data and parameters, and using an undefined machine learning module with no defined parameters or data.
iv. The rest of the claims are indefinite as depending from an indefinite claim.
Claim Rejections - 35 USC § 101
7. 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 9-31 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. The claim(s) recite(s) detecting tauopathy in a subject (independent claim 9), detecting amyloidogenic diseases in a subject (independent claim 19) and detecting or predicting tauopathy in a subject (in independent claim 27) based on a correlation between the presence of an increased level of p217+tau peptides in a plasma sample as compared to a predetermined threshold value and the presence of tauopathy or amyloidogenic disease including Alzheimer’s disease (AD) in patients suffering from tauopathy or amyloidogenic disease including. This correlation is a consequence of natural phenomenon in the plasma sample of patients having tauopathy or amyloidogenic disease including, which is a judicial exception. This judicial exception is not integrated into a practical application because the invention provides no improvement to any other technology or technical field (see MPEP 2106.05(a)) or transform into a different technology (see MPEP 2106.05(b)-(c)), does not apply or use a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition (see Vanda Memo), does not apply or use the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception (see MPEP 2106.05(e) and Vanda Memo). The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims recite elements/steps in addition to the judicial exception(s) that are well-understood, purely conventional or routine in the relevant field, the elements/steps recited in the claims in addition to the judicial exception(s) that are insignificant extra-solution activity, e.g., are merely appended to the judicial exception(s) and amount to nothing more than a mere field of use in view of MPEP 2106.05(d)-(h) and Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1361, 123 USPQ2d 1081, 1087 (Fed. Cir. 2017).
Claims 9-18 are drawn to a method of detecting tauopathy in a subject, comprising i) obtaining a plasma sample from the subject; ii) detecting an amount of p217+tau peptides in a subject using an assay, wherein the assay uses a capture antibody against a p217+tau epitope to form antibody-peptide complexes; and a detection antibody binding to the antibody-peptide complexes; and iii) determining the subject as having tauopathy or at risk of developing tauopathy, wherein the amount of the p217+tau peptides in the plasma sample is above a predetermined threshold value, wherein the predetermined threshold value is above a Lower Limit of Quantification (LLOQ) of the assay.
Claims 19-26 are drawn to a method of detecting amyloidogenic disease in a subject, comprising the same steps as set forth in claim 9 but are directed to determining the subject as having amyloidogenic disease or at risk of developing amyloidogenic disease based on the amount of the p217+tau peptides that is above the predetermined threshold value which is LLOQ.
Claims 27-31 are drawn to a method of detecting or predicting tauopathy in a subject, comprising (i) the same detecting step as set forth above in claim 9 and ii) generating tau data corresponding to the amount of the p217+tau peptides detected; iii) obtaining biomarker data corresponding to at least one biomarker detected from the subject, wherein the biomarker is selected from a group comprising NFL, adiponectin and leptin; and iv) comparing the tau data and biomarker data to a set of reference data using a machine learning module to determine or predict whether the subject has tauopathy or is at risk of developing tauopathy.
Based on the 101 analysis flowchart/the Alice/Mayo test and MPEP §§2106, 2106.03-2106.05(h), the claimed methods are not patent-eligible because the claims are directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. The instant claims merely recite observing naturally occurring biological correlations (i.e. the presence of an increased level of p217+tau peptides in a plasma sample of patients and the presence of tauopathy or amyloidogenic diseases in the patients) with no meaningful non-routine steps in between because the additional recited elements/steps only apply conventional techniques to detect this natural law (i.e. a known and conventional immunoassay, ELISA to detect the level of p217+tau peptides in a plasma sample of a patient with tauopathy or amyloidogenic diseases), which is similar to the claims that were directed to a discovery of a natural law, not as an improvement in the underlying immunoassay technology and recite no other inventive concept as affirmed by the United States Court of Appeals for the Federal Circuit. See Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1361, 123 USPQ2d 1081, 1087 (Fed. Cir. 2017).
Based on the Step 2A-Prong One of the 101 analysis flowchart/the Alice/Mayo test, the claims are directed to a law of nature or a natural phenomenon judicial exception because the claims recite detection of tauopathy or amyloidogenic disease in patients suffering from or suspected of having tauopathy or amyloidogenic diseases based on a correlation between the presence of an increased level of p217+tau peptides in a plasma sample of a patient and the presence of tauopathy or amyloidogenic diseases in patients suffering from or suspected of having tauopathy or amyloidogenic diseases. In addition, the limitation “determining the subject as having tauopathy or is at risk of developing ….when the amount of p217+tau peptides is above ….” in independent claims 9, 19 and dependent claims 12-15, 22-25 and the limitation “generating tau data, comparing the tau data…..” recited in claims 27-28 are mentally analyzing information to identify if a patient has an increased level of p217+tau peptides and whether the patient has tauopathy or amyloidogenic disease, which is a mental step-type abstract idea and thus a judicial exception. The increased level of p217+tau peptides in the plasma sample of patients having tauopathy or amyloidogenic diseases as compared to predetermined threshold value from reference controls is a law of nature or a natural phenomenon, which is a judicial exception. This correlation is a consequence of natural phenomenon, similar to the naturally occurring correlation found to be a law of nature by the Supreme Court in Mayo, and thus the claims are directed to a judicial exception (Step 2A Prong 1: YES).
This judicial exception is not integrated into a practical application because:
i) The invention provides no improvement to any other technology or technical field (see MPEP §2106.05(a)) because the claims themselves do not have any limitations that address this issue. The invention also does not use a judicial exception in conjunction with, a particular machine or to transform a particular technology to a different technology (See MPEP §2106.05 (b)-(c)). The recited immunoassay using a capture antibody and a detection antibody to measure and detect the level of p217+tau peptides in plasma sample of patients with tauopathy or amyloidogenic diseases is a well-known technique as evidenced by Mercken et al. (US10766953), Kolb et al.(US2019/0271710 or US10591492). Thus, the detecting step does not integrate the mental step of determining or the judicial exception into a practical application because the use of a capture antibody against p217+tau peptides and a detection antibody for the antibody- p217+tau peptide complexes in an immunoassay is well known and provides no improvement in technology or transform the technology.
ii) The invention does not apply or use a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition (see Vanda Memo) because the claims themselves do not have any limitations that address these issues;
iii) The invention does not apply or use the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception (see MPEP 2106.05(e) and Vanda Memo). The claims recite a natural correlation between an increased level of p217+tau peptides and tauopathy or amyloidogenic disease (law of nature). The detecting steps provide insignificant extra-solution activity and mere data gathering as determined by the court. See Mayo, 566 U.S. at 79, 101 USPQ2d at 1968 and PerkinElmer, Inc. v. Intema Ltd., 496 Fed. App'x 65, 73, 105 USPQ2d 1960, 1966 (Fed. Cir. 2012) and MPEP §2106.05(g). The detecting step only generally links the use of the judicial exception (diagnose or detect tauopathy or amyloidogenic diseases based on an increased level of p217+tau peptides) to a well-known immunoassay, which is merely extra-solution activity or a field of use, and thus only provides a nominal or insignificant relationship to the exception(s) and is merely extra-solution activity or a field of use. See MPEP 2106.05(g)-(h). Thus, the additional element or the detecting step does not integrate the judicial exception into a practical application (Step 2A Prong 2: NO).
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims recite elements/steps in addition to the judicial exception(s) that are well-understood, purely conventional or routine in the relevant field, the elements/steps recited in the claims in addition to the judicial exception(s) that are insignificant extra-solution activity, e.g., are merely appended to the judicial exception(s) and amount to nothing more than a mere field of use (see MPEP 2106.05 (d) & (a)-(c) & (g)-(h)). The additional elements/steps “obtaining a plasma sample, contacting the plasma with a capture antibody, contacting with a detection antibody” “detecting an amount…” and “determining based on the amount of …above a predetermined threshold value….” are routine and conventional in the relevant field to detect and measure the level of p217+tau peptides in a bodily sample, such as plasma, serum or CSF, as evidenced by Mercken et al. (US10766953), Kolb et al.(US2019/0271710 or US10591492) and are mere data gathering and the activity that the courts have found to be insignificant extra-solution activity. See Mayo, 566 U.S. at 79, 101 USPQ2d at 1968 and PerkinElmer, Inc. v. Intema Ltd., 496 Fed. App'x 65, 73, 105 USPQ2d 1960, 1966 (Fed. Cir. 2012).
The claims are not directed to new techniques for performing an immunoassay to detect levels of a patient’s p217+tau peptides in the plasma. They only recite applying known methods to detect levels of p217+tau peptides in the plasma, comparing them to control levels, and reaching a conclusion that the levels of patient’s plasma p217+tau peptides are elevated in comparison to those of controls. This conclusion is simply another articulation of the natural law that plasma p217+tau peptides levels correlate with tauopathy or amyloidogenic diseases, which is similar to the claims that were directed to a patentable-ineligible natural law and recite no other inventive concept as held by the Courts in Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1355, 1362, 123 USPQ2d 1081, 1082-83, 1088 (Fed. Cir. 2017). Thus, the additional elements/steps recited in the claims are a well-understood, purely conventional or routine in the art or relevant field to detect and determine the p217+tau peptides in a plasma sample obtained from an adult patient. These additional elements/steps do not amount to significantly more than the exception itself because the additional recited steps only apply conventional techniques (i.e. an immunoassay to detect p217+tau peptides) to detect the natural law (i.e. an increased p217+tau peptides in the plasma in patients with tauopathy or amyloidogenic diseases), which is similar to the claims that were ruled as directed to a natural law and lacking an inventive concept and further affirmed by the Courts in Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1355, 1362, 123 USPQ2d 1081, 1082-83, 1088 (Fed. Cir. 2017).
The combination of judicial exception with additional elements is insufficient to ensure that the claims amount to significantly more than the exception itself because these additional elements or steps are mere field of use that impose no meaningful limit on the performance of the method and are no more than well-understood, purely conventional, and routinely taken by others in order to apply the natural principle (Step2B: NO). Accordingly, claims 9-31 are not patent eligible because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
Claim Rejections - 35 USC § 112
8. The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 27-31 are rejected under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph, as based on a disclosure which is not enabling. The disclosure does not enable one of ordinary skill in the art to practice the invention without the elements/steps of how to determine or predict whether the subject has tauopathy is at risk of developing tauopathy and without specific parameters based on comparison of a defined and specific reference data and parameters, and using a defined machine learning module with defined parameters or data, which are critical or essential to the practice of the invention but not included in the claim(s). See In re Mayhew, 527 F.2d 1229, 188 USPQ 356 (CCPA 1976). The claims recite no elements/steps of how to determine or predict whether the subject has tauopathy is at risk of developing tauopathy, or no specific parameters based on comparison of defined and specific reference data and parameters, and/or no defined machine learning module with defined parameters or data. Thus, a skilled artisan cannot contemplate how to determine or predict whether the subject has tauopathy or is at risk of developing tauopathy without specific parameters based on comparison of undefined reference data and parameters, and/or using an undefined machine learning module with no defined parameters or data.
Claim Rejections - 35 USC § 112
9. Claims 6-7 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The invention appears to employ novel biological materials, specifically a capture antibody pT3 and a detection antibody pT82. Since the biological materials are essential to the claimed invention they must be obtainable by a repeatable method set forth in the specification or otherwise readily available to the public. If the biological materials are not so obtainable or available, the requirements of 35 U.S.C. § 112 may be satisfied by a deposit of the biological materials. The specification does not disclose a repeatable process to obtain the biological materials and it is not apparent if the biological materials are readily available to the public. There is no indication that the claimed pT3 and pT82 antibodies are public availability. If the deposit is made under the Budapest Treaty, then an affidavit or declaration by Applicant, or a statement by an attorney of record over his or her signature and registration number, stating that the specific biological materials have been deposited under the Budapest Treaty and that the biological materials will be irrevocably and without restriction or condition released to the public upon the issuance of a patent, would satisfy the deposit requirement made herein. If the deposit has not been made under the Budapest Treaty, then in order to certify that the deposit meets the criteria set forth in 37 C.F.R. §§ 1.801-1.809, Applicant may provide assurance of compliance by an affidavit or declaration, or by a statement by an attorney of record over his or her signature and registration number, showing that:
(a) during the pendency of this application, access to the invention will be afforded to the Commissioner upon request;
(b) all restrictions upon availability to the public will be irrevocably removed upon granting of the patent;
(c) the deposit will be maintained in a public depository for a period of 30 years or 5 years after the last request or for the effective life of the patent, whichever is longer;
(d) a test of the viability of the biological material at the time of deposit will be made (see 37 C.F.R. § 1.807); and
(e) the deposit will be replaced if it should ever become inviable.
Applicant’s attention is directed to M.P.E.P. §2400 in general, and specifically to §2411.05, as well as to 37 C.F.R. § 1.809(d), wherein it is set forth that “the specification shall contain the accession number for the deposit, the date of the deposit, the name and address of the depository, and a description of the deposited material sufficient to specifically identify it and to permit examination.” The specification should be amended to include this information, however, Applicant is cautioned to avoid the entry of new matter into the specification by adding any other information. Finally, Applicant is advised that the address for the ATCC should appear in the specification. The address is:
American Type Culture Collection
10801 University Boulevard
Manassas, VA 20110-2209
Claim Rejections - 35 USC § 112
10. Claims 1-31 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof.
Claims 1-31 encompass using a genus of capture antibody directed against p217+tau peptide, a genus of detection antibody binding to the capture antibody-p217+tau peptide complex.
Claims 4-5 encompass using a genus of capture antibody binding to an epitope containing amino acids (aa) 210-220 of human tau protein and using a genus of detection antibody binding to an epitope comprising aa 7-20 or aa 116-127 of human tau protein.
Claims 9-26 encompass using a genus of predetermined threshold value and a genus of lower limit of quantification (LLOQ).
Claims 27-31 encompass using a genus of a set of reference data and a genus of machine learning module.
The specification only describes a capture antibody pT3 and hT7, wherein the pT3 comprises a heavy chain variable region (VH) of SEQ ID NO:19 and a light chain variable region (VL) of SEQ ID NO:2 or a VH of SEQ ID NO:21 and a VL of SEQ ID NO:22; and wherein the hT7 is commercially available from ThermoFisher company (Catalog #: MN1000). The specification only describes a detection antibody hT43 and pT82, wherein the hT43 comprises a VH of SEQ ID NO:16 and a VL of SEQ ID NO:17, and the pT82 comprises a VH of SEQ ID NO:8 and a VL of SEQ ID NO:9. The specification also only describes using data from “a panel of 23 blood-based biomarkers including p217+Tau, NFL, adiponectin, leptin and other inflammatory and metabolic markers from 199 subjects having mild to moderate AD…..the amount of p217+tau peptides measured from CSF of the subject exceeded 21 pg/mL, this concentration corresponds to a commonly used cutoff of 70 pg/mL with Innotest p181-tau for defining “T” status. Data corresponding to the 23 biomarker measurements and p217+tau measurements in CSF, along with patient demographic data (e.g., age and sex) for all 199 subjects were then separated into two different data sets: a training set (n=150) and a holdout set (n=49). ….”, and using a plurality of ensemble machine learning modules including a support vector machine module, a random forest module, a logistic regression module, a gradient boosting module to generate an outcome. The specification states that that the AUC of the ROC curve without any biomarker data is 0.59”, the AUC of the ROC curve that uses p217+tau measurements from serum is 0.87, the AUC of the ROC curve that uses p217+tau measurements from serum and data for NFL is 0.92, the AUC of the ROC curve that uses p217+tau measurements from serum, and data for NFL and adiponectin is 0.92 and that “When the machine learning analysis includes all 4 biomarkers (p217+tau measurements from serum, and data for NFL, adiponectin and leptin) as features, accuracy was at 0.84” (see Example 15, paragraphs [0228]-[0240]).
However, the claims are not limited to pT3 or hT7 as a capture antibody, hT43 or pT82 as a detection antibody or the ensemble machine learning module and data set forth above but also encompass using structurally and functionally undefined capture antibodies and detection antibodies, and undefined data and machine learning modules.
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant is in possession of and what Applicant is claiming.
M.P.E.P. § 2163 instructs:
An invention described solely in terms of a method of making and/or its function may lack written descriptive support where there is no described or art-recognized correlation between the disclosed function and the structure(s) responsible for the function. . . .
An applicant may show possession of an invention by disclosure of drawings or structural chemical formulas that are sufficiently detailed to show that applicant was in possession of the claimed invention as a whole. . . .
An applicant may also show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics.”
This standard has not been met in this case. From the specification, it is clear that Applicant is in possession of using pT3 or hT7 as a capture antibody; hT43 or pT82 as a detection antibody or data for training and the ensemble machine learning module shown in Example 15. However, Applicant is not in possession of other structurally and functionally undefined capture antibodies and detection antibodies, and undefined data and machine learning modules in the claimed methods.
As an initial matter, Applicant has provided no structures or sequences sufficiently detailed to show that he/she was in possession of the claimed invention as a whole. There was also no known or disclosed correlation between the required function (i.e. binding to p217+tau peptide for a capture antibody, binding to the capture antibody-p217+tau peptide complex for a detection antibody, binding to an epitope containing aa 210-220 of human tau protein for a capture antibody and binding to an epitope comprising aa 7-20 or aa 116-127 of human tau protein for a detection antibody) and any particular structure or sequence.
The specification provides no identification of any particular portion of the structure that must be conserved for the claimed genus of capture antibodies directed against p217+tau peptide, the claimed genus of detecting antibody binding to the capture antibody-p217+tau peptide complex, the claimed genus of capture antibody binding to an epitope containing aa 210-220 of human tau protein and the claimed genus of detecting antibody binding to an epitope comprising aa 7-20 or aa 116-127 of human tau protein.
The specification fails to provide sufficient description as to what structures or sequences for the claimed capture and detection antibodies or their corresponding heavy chain, light chain, variable regions, or H/LCDRs1-3 are in order to generate antibodies with the claimed binding ability or features and what sequences can be changed or not changed in order to have the claimed binding ability or features except pT3 or hT7 for a capture antibody, and hT43 or pT82 for a detection antibody.
Applicant has not disclosed sufficient species for the broad genus of capture antibodies directed against p217+tau peptide, the broad genus of detecting antibody binding to the capture antibody-p217+tau peptide complex, the broad genus of capture antibody binding to an epitope containing aa 210-220 of human tau protein and the claimed genus of detecting antibody binding to an epitope comprising aa 7-20 or aa 116-127 of human tau protein.
In light of Amgen, Inc. v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017), describing a “fully characterized antigen” for an antibody is no longer adequate on its own to demonstrate possession of the antibody. Based on MPEP§2161.01 and 2163, the USPTO guidance regarding written description requirement of 35 U.S.C.§C112 (a), specifically concerning the written description requirement for claims drawn to antibodies and Federal Circuit decisions, when an antibody is claimed, 35USC112(a) requires adequate written description of the antibody itself. See Amgen 872 F.3d at 1378-79.
The court of the Federal Circuit also stressed that the “newly characterized antigen" test could not stand because it contradicted the quid pro quo of the patent system whereby one must describe an invention in order to obtain a patent. See Amgen, 872 F.3d at 1378-79, quoting Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1345 (Fed. Cir.2010). In view of the Amgen decision, adequate written description of a newly characterized antigen alone should not be considered adequate written description of a claimed antibody to that newly characterized antigen, even when preparation of such an antibody is routine and conventional.
The specification also provides no identification of any particular common feature and characteristic for the claimed genus of re that must be conserved for the claimed genus of predetermined threshold value, the claimed genus of lower limit of quantification (LLOQ), the claimed genus of a set of reference data and the claimed genus of machine learning module.
Since the common characteristics/features of other antibodies containing structurally and functionally undefined sequences are unknown and other predetermined threshold value, lower limit of quantification (LLOQ), other sets of reference data and other machine learning modules are unknown, a skilled artisan cannot envision the functional correlations of the genus with the claimed invention. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the genera of capture antibodies and detection antibodies, predetermined threshold value, LLOQ, a set of reference data and machine learning module.
Based on MPEP § 2161.01 and §2163, “to satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116”.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of capture antibodies and detection antibodies, predetermined threshold value, LLOQ, a set of reference data and machine learning module, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483.
Therefore, the claimed methods have not met the written description provision of 35 U.S.C. §112, first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115). Applicant is directed to the Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, ¶ 1 "Written Description" Requirement. See MPEP § 2161.01 and 2163.
11. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Claim Rejections - 35 USC § 102
12. 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 1-26 are rejected under 35 U.S.C. 102(a)(1) &(a)(2) as being anticipated by Kolb et al. (US2019/0271710, published Sep 5, 2019, priority Mar 5, 2018; issued as US10591492).
Claims 1-8 are drawn to an assay method of detecting p217+Tau peptides in a subject, comprising: i) obtaining a plasma sample from the subject; ii) contacting the plasma sample with a capture antibody directed against a p217+Tau peptides to form antibody-p217+Tau peptide complexes; iii) contacting the antibody-p217+Tau peptides complexes with a detection antibody; iv) detecting the detection antibody to determine an amount of the p217+Tau peptides in the plasma sample. Dependent claims are directed to wherein the capture antibody is immobilized on a solid phase including a magnetic bead (claims 2-3), wherein the capture antibody binds to an epitope containing amino acids (aa) 210-220 of human tau protein (claim 4) or the detection antibody binds to an epitope comprising aa 7-20 or aa 116-127 of human tau (claim 5), wherein the capture antibody is pT3, the detection antibody is pT82 (claims 6-7), wherein the plasma sample is diluted with a sample diluent comprising at least one of a non-ionic surfactant and tris(hdroxymethyl)aminomethane (Tris buffer) (claim 8).
Claims 9-26 are drawn to methods of detecting tauopathy or amyloidogenic disease in a subject and detecting amyloidogenic diseases in a subject, comprising i) obtaining a plasma sample from the subject; ii) detecting an amount of p217+Tau peptides in the sample using an assay of claim 1 above and iii) determining the subject as having tauopathy or amyloidogenic disease, or at risk of developing tauopathy or amyloidogenic disease when the amount of p217+Tau peptide is above a predetermined threshold value, wherein the predetermined threshold value is above a Lower Limit of Quantification (LLOQ) of the assay. Dependent claims are directed to the assay does not concentrate the p217+Tau peptides from the plasma sample by immunoprecipitation before measuring the amount of the p217+Tau peptides present, wherein the plasma sample is crude plasma (claims 10-11 and 20-21), wherein the LLOQ corresponds to a 15-25%, 20% coefficient of variation (CV) of the assay (claims 12-13 and 22-23), wherein the predetermined threshold value is at least 3 or 10 times of LLOQ (claims 14-15 and 24-25), wherein the tauopathy includes familial/sporadic Alzheimer’s disease (AD) (claims 16-17 and 26).
Kolb et al. (US2019/0271710) teaches an assay method of detecting p217+Tau peptides in a subject (see abstract; para. [0008]-[00021]; [0097]; [0098]) and detecting tauopathy or amyloidogenic disease including AD and progressive supranuclear palsy and diseases recited in claim 16 (see para. [00024]-0034]; [0096]; [0124]-[0151]) in a subject based on detection of an increased level of p217+Tau peptides in a plasma sample of subjects using a capture antibody directed against p217+Tau (see para.[0029]-[0032]) and a detecting antibody that binds to the antibody-p217+Tau peptides complex in an ELISA, immunohistochemistry, western blot, or in vivo imaging methods; wherein the capture antibody includes pT3 antibody (see para. [0084]; [0089]; [0092]-[0093]) and the detection antibody includes pT82 (see para. [0030]; [0037]; [0092]-[0093];[0112]; [0150], Example 1, [0219]-[0231]), which meet the limitations recited in instant claims 1-26 (see paragraphs [0011]; [0012]-[0015];[0016]-[0034]; [0083]-[0094]; [0096]; [0107]-[0122]; [0124]-[0151], [0161]-[0199]; [0219]-[0316], Examples 1-9, claims 1-18) . Kolb also teaches methods of detecting tauopathy or amyloidogenic disease including AD and progressive supranuclear palsy diseases recited in claim 16 in a subject based on the above assay and detection of an increased level of p217+Tau peptides in a plasma sample of the subject, which meets the limitations recited in claims 9-26 (see paragraphs [0011]; [0012]-[0015];[0016]-[0034]; [0083]-[0094]; [0096]; [0107]-[0122]; [0124]-[0151], [0161]-[0199]; [0219]-[0316], Examples 1-9, claims 1-18).
Kolb teaches that the capture antibody is immobilized on a solid phase including a magnetic bead as in claims 2-3 (see para. [0089];[0146]; [0154]; [0169];[0219]; [0226];[0236]; [0258]). The capture antibody pT3 disclosed by Kolb binds to an epitope containing aa 210-220 of human tau protein as in claim 4 and is identical to the capture antibody pT3 recited in claim 6 (see para. [0084]). The detection antibody pT82 disclosed by Kolb binds to aa 7-20 or aa 116-127 of human tau as in claim 5 and is identical to the capture antibody pT82 recited in claim 7 (see para. [0091]-[0092]; [0257]). Kolb also teaches that the plasma sample is diluted with a sample diluent comprising at least one of a non-ionic surfactant, Tween 20 and tris(hdroxymethyl)aminomethane (Tris buffer) as in claim 8 (see para. [0220]). Kolb teaches that the plasma sample is crude plasma as in claims 20-21 and also meets the limitation that the assay does not concentrate the p217+Tau peptides from the plasma sample by immunopreciptation before measuring the amount of the p217+Tau peptides present as in claims 10-11 (see para. [0327]-[0329]). Kolb teaches that the determining step is based on comparison with a predetermined threshold value, wherein the predetermined threshold is above LLOQ and the LLOQ corresponds to <20%, which meets the limitation “15-25% or 20% coefficient of variation (CV) of the assay” as in claims 12-13 and 22-23 (see para. [0259]-[0264], Example 7, tables 2-4). Kolb teaches that the predetermined threshold value is at least 3 or 10 times of LLOQ as in claims 14-15 and 24-25 (see para. [0259]-[0268], Tables 2-4). Kolb teaches tauopathy, familial/sporadic AD and progressive supranuclear palsy and other diseases recited in claims 16-17 and 26 (see para. [0024]-[0026];[0096];[0135]-[0137], [0176]-[0177], claims 1-18). Thus, claims 1-26 are anticipated by Kolb et al. (US2019/0271710).
Double Patenting
13. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the claims at issue are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 4-23 of U.S. Patent No. 10591492. Although the claims at issue are not identical, they are not patentably distinct from each other because the methods recited in claims 4-23 of the ‘492 patent anticipate the methods recited in instant claims. The ‘492 patent claims a method of measuring p217+tau peptides in a sample including plasma sample using a capture antibody comprising HCDRs1-3 of SEQ ID NOs:32-34 respectively and LCDRs1-3 of SEQ ID NOs: 35-37 respectively against p217+tau and a detection antibody comprising HCDRs1-3 of SEQ ID NOs: 11-14 respectively and LCDRs1-3 of SEQ ID NOs:15-17 respectively to measure an amount of the p217+tau and also using the detection method to determine whether a subject suffers from tauopathy including AD based on an increased amount of p217+tau compared to the baseline. The ‘492 patent's claims are a species of the generic method recited in instant claims and thus, anticipate the instant claims. Therefore, instant claims 1-26 are not patentably distinct from claims 4-23 of the ‘492 patent because instant claims 1-26 are anticipated by claims 4-23 of the ‘492 patent.
Double Patenting
14. Claims 1-26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of copending Application No. 18/875041, claims 22-41 of copending Application No. 19/201475 or claims 1, 3-9, 13-24 of copending Application No. 19/512016. Although the claims at issue are not identical, they are not patentably distinct from each other because the methods recited in claims 1-24 of the Application No. 18/875041 (the ‘041 Application), claims 22-41 of the Application No. 19/201475 (the ‘475 Application) or claims 1, 3-9, 13-24 of the Application No. 19/512016 (the ‘016 Application) anticipate the methods recited in instant claims. The ‘041 Application, the ‘475 Application or the ‘016 Application claims methods of measuring p217+tau peptides in a sample including plasma sample using a capture antibody comprising HCDRs1-3 of SEQ ID NOs:32-34 respectively and LCDRs1-3 of SEQ ID NOs: 35-37 respectively against p217+tau and a detection antibody comprising HCDRs1-3 of SEQ ID NOs: 11-14 respectively and LCDRs1-3 of SEQ ID NOs:15-17 respectively to measure an amount of the p217+tau and also claims methods of using the detection method to determine whether a subject suffers from tauopathy or amyloidogenic disease including AD and progressive supranuclear palsy and other diseases recited in claims 16-18 and 26 based on an increased amount of p217+tau compared to the baseline. The ‘041 Application’s claims, the ‘475 Application’s claims or the ‘016 Application’s claims are a species of the generic method recited in instant claims and thus, anticipate the instant claims. Therefore, instant claims 1-26 are not patentably distinct from claims 1-24 of the ‘041 Application, claims 22-41 of the ‘475 Application or claims of 1, 3-9, 13-24 of the ‘016 Application because instant claims 1-26 are anticipated by claims 1-24 of the ‘041 Application, claims 22-41 of the ‘475 Application or claims 1, 3-9, 13-24 of the ‘016 Application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
15. NO CLAIM IS ALLOWED.
16. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Mercken et al. (US10766953, issued Sep 8, 2020, priority Mar 16, 2017) teaches a method of detecting the presence of phosphorylated PHF-tau in a subject or a method of diagnosing a tauopathy in a subject by detecting the presence of PHF-tau in the subject using an anti-PHF-tau antibody including the claimed pT3 as a capture antibody and a detection antibody (see col. 5, lines 25-30; col. 10, lines 52-62; col. 12, lines 63-col.13, line 14; col. 13, lines 31-col. 27, line 15; col. 28, line44-col.29, line 42; col. 33, lines 36-50; col.57, line 16-60, table 20).
17. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHANG-YU WANG whose telephone number is (571)272-4521. The examiner can normally be reached on Monday-Thursday, 7:00am-5:00pm EST.
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Chang-Yu Wang
August 5, 2026
/CHANG-YU WANG/Primary Examiner, Art Unit 1675
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