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 .
DETAILED ACTION
Claims 1-30 are pending and examined on merits in this office action.
Drawings
The drawings filed on 07/03/2024 are objected to because the images are blurry. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required. 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). The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-30 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.
Claims 1, 29 and 30 recite a process of ADA bridging immunoassay wherein the process steps require incubating a sample with a capture drug labelled with a first label, a detection drug labelled with a second label, a drug target blocking reagent for forming a bridging complex. The capture drug, the detection drug and the target blocking reagent have not been defined in the claim and thus the relationship of the interaction of the various components with ADA in the ADA bridging assay is vague and indefinite. Claims 2-28 carry the same indefiniteness as the claims are directly or indirectly dependent on claim 1.
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 1-30 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1, 29 and 30 are directed to a method of drug target interference assay comprising: contacting serum sample with a capture drug labelled with a first label; a detection drug labelled with a second label; and a drug target blocking reagent; incubating the serum sample, under mild basic pH assay condition, with the capture drug, the detection drug, the drug target blocking reagent, and allowing the drug target blocking reagent to bind to the drug target present in the sample.
The “drug” encompasses a large number of therapeutic proteins based on their molecular types that include antibody-based drugs, Fc fusion proteins, anticoagulants, blood factors, bone morphogenetic proteins, engineered protein scaffolds, enzymes, growth factors, hormone, interferons interleukins and thrombolytics and thus drug targets for the various types of therapeutic proteins also includes an inordinately a large number of distinct compounds. Therefore, as required, the claim encompasses an enormous number of different drug-target blocking reagent for the enormous number of drug targets, with includes various antibodies and protein directed to various drug target (see claims 2-8).
However, throughout the specification, the examples and description for mitigation of drug target interference by incubating the serum sample with the capture drug, detection drug and drug target blocking reagent under mild basic pH conditions utilizing ADA bridging immunoassay are limited with human therapeutic antibody as drug and human anti-target antibody (HuAb1 and HuAB1) as target blocking reagent. Throughout the specification, the incubation under mild basic pH assay condition for the ADA bridging immunoassay for the method of mitigation of drug target interference is very limited for therapeutic monoclonal antibody for multimeric target and wherein the target booking reagent is limited to HuAb1 and HuAb2 and therein is not a single example of mitigation with mild basic pH condition with various other target blocking reagent.
A disclosure of ADA assay at a basic pH condition for a human therapeutic antibody drug with a multimeric drug target and with an anti-target antibody HuAb1 and/or HuAb2, does not provide representative example and disclosure of ADA assays for the various therapeutic proteins, various drug target and with various drug target binding molecules as encompassed by the scope of the claims.
A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that “only describe[d] one type of structurally similar antibodies” that “are not representative of the full variety or scope of the genus.”). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) (“[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.”). “A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed.” In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004). Emphasis added.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-30 are rejected under 35 U.S.C. 103 as being unpatentable over Dai et al (AAPS J, 2014; Cite # 4, IDS filed on 3/10/2025).
Dai describes the development of a method that eliminates falsepositive results due to nerve growth factor (NGF) interference I in the assessment of fulranumab immunogenicity. Fulranumab is a human lgG2 monoclonal antibody (i.e. a drug) that neutralizes NGF (i.e. target of the drug: drug target) and is in development for the treatment of pain. An immunogenicity test method performed in phase 1 studies was found to be prone to NGF interference, leading to a high apparent incidence of anti-drug antibody (ADA). The ADA immunoassay comprised a homogeneous bridging electrochemiluminescence (ECL) format with biotin and ruthenium-labeled fulranumab (i.e. a capture drug labeled with first label biotin and a detection drug labeled with a second label) bound together ("bridged") by ADA in test samples for detection
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. In this assay, NGF (i.e. the drug target) produced a false-positive signal due to its ability to bridge fulranumab molecules
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. To develop a specificity assay to eliminate the NGF false-positive results due to drug and to drug target interferences, Dai discovered that the acid-dissociation-based pretreatment of samples used for mitigating drug interference dramatically increased drug target interference. The best strategy to eliminate the NGF interference was to use competitive inhibition with fulranumab and utilize an alternative NGF binding antibody (i.e. a drug target blocking reagent) to eliminate NGF interference and produce true fulranumab specific ADA results. Using this new method, Dai confirmed that the high apparent antifulranumab antibody incidence (>60%) in clinical study samples was in fact due to fulranumab-bound NGF released during the acid-dissociation step of the ADA testing method. Dai conclude that their revised method accurately identifies anti-fulranumab antibodies by incorporating steps to eliminate fulranumab and NGF interference.
Dai does not disclose incubating the sample under mild basic pH assay condition, with the capture drug, detection drug and the drug target blocking reagent.
Dai however, teaches that acid treatment step can displace not only ADA but also target bound to drug and this phenomenon lead to false-positive signals in a majority of the samples (page 475, 1st col., 2nd paragraph) and suggested acid-dissociation pretreatment must not be universally applied to improve ADA assays without investigating its bioanalytical risks versus benefits (Abstract; page 468, 2nd paragraph of 2nd col.).
Therefore, carrying out the binding steps in a neutral assay condition or a slight basic condition would be obvious for routine optimization and would be within the purview of one of ordinary skilled in the art.
In regard to claims 3 and 4, Dai discloses NGF binding antibody as a blocking reagent, which can be considered as receptor and the NGF as ligand.
In regard to claims 2 and 5-8, as described above, Dai discloses ADA bridging immunoassay and discloses anti-NGF antibody and NGF-blocking protein (anti-NGF TrkA peptide fused to human Fc) (page 465, 2nd col.). Since the basic concept has been disclosed by Dai, one of ordinary skilled in the art can easily envisage mitigation method for various other ADA bridging agent depending on various drugs and depending on the various drugs, various blocking proteins would be obvious to one of ordinary skilled in the art.
In regard to claims claim 12-14, Dai discloses Falranumab monoclonal antibody, which is a therapeutic drug and which is human IgG2 monoclonal antibody (page 475).
In regard to claims 15 and 16, NGF is soluble, multimeric (page 475, 1st col, 2nd para) and is a homodimeric drug target (see “conclusion”, page 476).
In regards to claims 17-19, Dai teaches samples were diluted to 10% in 300 mM acetic acid in a nonbinding polypropylene deep well plate to enable antibody-drug complex dissociation before analysis. Acidified samples were incubated for 30 to 60 min with shaking at ambient temperature. MSD Streptavdin coated plates were blocked for 30–60 min at room temperature with 300 μL/well of PBS buffer containing 1% BSA. Twenty-five microliters of the acidified sample was transferred to the blocked MSD plates, then 25 μL of master-mix reagent containing 0.25 μg/mL of biotinylated fulranumab and 0.25 μg/mL of ruthenylated fulranumab with 1% BSA in PBS and 0.3 M of a Tris base solution (1 M, pH 9.5) were added to each well of the MSD plate with acid-treated samples. The MSD plates were incubated for 2 h in the dark with shaking. The MSD plates were washed and 150 μL of 2×MSD Read T-Buffer was added per well before the plates were read on an MSD Sector® Imager 6000 (page 466, 1st col., “Bridging ECLIA for fulranumab ADA assay”). Therefore, it would be highly expected that the 25ul of acidified sample added in the assay buffer of Tris base solution of pH 9.5 would provide a condition of mild basic pH assay condition within the pH range of about 7.5 and about pH 9.5 and selection of a particular pH within the range would be considered routine optimization.
In regard to claim 20 and 21, Dai discloses sample is serum samples treated with fulranamab (i.e. drug) (Page 468, 1st col.).
In regard to claim 22, Dai teaches incubating for complex formation at room temperature (page 468, 2nd col.).
In regards to claims 2 and 23-25, as described above, Dai discloses the basic concept to utilizing drug target blocking reagent in a ADA bridging immunoassay with a teaching of avoiding acidic condition and thus automation and designing various assays including utilizing microtiter plate for high-throughput detection while keeping in mind of the basic concept, would be considered obvious to one of ordinary skilled in the art.
In regard to claims 26-28, as described above, Dai discloses ADA immunoassay comprised a homogeneous bridging electrochemiluminescence (ECL) format with biotin and ruthenium-labeled fulranumab (i.e. a capture drug labeled with first label biotin and a detection drug labeled with a second label) bound together ("bridged") by ADA in test samples for detection and discloses streptavidin plates (page 466).
In regards to claims 9-11, 29 and 30, since the basic concept of mitigation by utilizing binding agent for drug target in ADA assay has been taught by Dai and since Dai discloses anti-NGF antibody and NGF-blocking protein (anti-NGF TrkA peptide fused to human Fc) (page 465, 2nd col.) as drug target binding agent, one of ordinary skilled in the art can easily envisage utilizing both the binding agent during the ADA bridging process in the mitigation process with the expectation of efficient removal of drug target and removing interference with a reasonable expectation of success.
Double Patenting
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 conflicting claims 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); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP §§ 706.02(l)(1) - 706.02(l)(3) for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) 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 www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of US patent 12055551 (Cite #2, IDS filed on 3/10/2025). Although the claims at issue are not identical, they are not patentably distinct from each other because the subject matter of instant claims are broadly encompassed by the claims of US Patent ‘551. Claim 1 of US Patent ‘551 teaches a method comprising: contacting the sample with a first labeled drug, contacting the sample with a second labeled drug, contacting the sample with a binding partner of a target, and detecting the presence of a complex which comprises the first labeled drug, the anti-drug antibody and the second labeled drug; wherein the sample comprises the anti-drug antibody and the target, and wherein the target is a binding partner of the drug.
In regard to claims 1, 29 and 30, the claims of US application ‘566 disclose the following:
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Thus, the subject matter of claims 1, 29 and 30 are broadly disclosed in the above claim 1.
In regard to claims 2-28, the subject matter of the dependent claims are disclosed throughout claims 2-23 of US patent ‘551.
Conclusion
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/SHAFIQUL HAQ/Primary Examiner, Art Unit 1678
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