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 .
Election/Restrictions
Applicant’s election of the species of first reactant and SEQ ID NO: 12 in the reply filed on 5/13/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). After further consideration, the species requirement between first antibody and first reactant is no longer required.
Claims 6 and 12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 5/13/2026.
Claims 1-5, 7-11 and 13 are under consideration in the instant Office Action.
Information Disclosure Statement
The listing of references in 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, they have not been considered.
Claim Interpretation
Claim 2 has optional language for “…a step of optionally recovering a first antibody-analyte complex contained in the first reactant…”. Due to the optional language this step is being interpreted as not being required as part of the method.
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 1-5, 7-11 and 13 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 1-2, 7-8 and 13 call for monoclonal antibody recognizing a linear epitope and a monoclonal antibody recognizing a conformational epitope. Antibodies are specialized proteins that bind specific epitopes. The term “recognizing” is vague and indefinite since it is unclear how an antibody recognizes an epitope? Antibodies only bind epitopes.
Dependent claims do not overcome this indefiniteness issue and therefore, suffer from the same issue as the claims they depend from.
Further, claims 7 and 13 indefinite since the claims are using parenthesis around the amino acid sequences and their sequence identifiers. The fact that the amino acids and the SEQ ID NOs are in parenthesis make it is unclear what is being set forth. This is being interpreted as the phrase "for example" which renders the claim indefinite because it is unclear whether the limitations following the parenthesis are part of the claimed invention. Further, the sequence identifiers are also confusing and unclear what they are referring to since they are found within the parenthesis and only allowed used use of parenthesis in claim is to indicate abbreviations of terminology.
Accordingly, the metes and bounds of the claims cannot be determined.
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 1-2, 7 and 13 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 7 and 13 are is directed to any monoclonal antibody which recognizes the conformation of the amino acid sequence of SEQ ID NO:12. As such, the claim is directed to an antibody defined entirely by function (binding). See MPEP §2163(I)(A) which states:
"The claimed invention as a whole may not be adequately described where an invention is described solely in terms of a method of its making coupled with its function and there is no described or art recognized correlation or relationship between the structure of the invention and its function. A biomolecule sequence described only by a functional characteristic, without any known or disclosed correlation between that function and the structure of the sequence, normally is not a sufficient identifying characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.”
In this case, antibodies generally share certain characteristics such as Fc regions or hinge regions. However, these structures are not correlated with the binding function of the antibody. The hyper variable regions (HVRs), i.e., complementarity determining regions (CDRs) of an antibody, are well established in the art as the portion of the binding region which imparts the specificity of an antibody. However, there is no way to a priori look at an antigen sequence PIVKA-II of SEQ ID NO: 12 and envisage the combination of six CDRs that will bind that antigen. First, even highly related CDRs may not bind the same target. See for example Kussie 1994 (instant PTO-892) who demonstrates that a single amino acid change in the heavy chain of an antibody which binds p-axophenylarsonate (Ars) completely abrogates the ability of the antibody to bind Ars but adds the functionality of binding the structurally related p-azophenylsulfonate (e.g., abstract). Second, even when provided with several related antibodies that bind the desired target, this does not represent the astronomical and potentially unknowable breadth of all possible amino acid sequences which will result in the desired binding properties. This is exemplified by the Court decision in Abbvie (Abbvie v Janssen 759 F.3d 1285 (Fed. Cir. 2014)), where Abbvie developed over 200 antibodies that shared 99.5% identity in the variable regions (p.7) and which bound the target, but in no way allowed one to envisage the unique structure of Centocor’s antibodies which bound the same target but shared only 50% sequence similarity (see table on page 11).
Thus, the art recognizes that the CDRs define the binding properties of an antibody and that even single amino acid changes to this region can completely abrogate the binding specificity of an antibody. As a further example, see Chen 1995 (instant PTO-892) which demonstrates single amino acid changes in the VH CDR2 sequence can increase binding, decrease binding, destroy binding, or have no effect on binding when compared to the wild-type antibody.
Thus, making changes to the CDR sequence of an antibody is a highly unpredictable process and the skilled artisan could not a priori make any predictions regarding such mutations with any reasonable expectation of success nor envisage the breadth of structurally unrelated CDR combinations that would still possess the required functions.
The specification discloses certain specific antibodies, with their own designations but fails to teach any specific antibody structures that would demonstrate they are in possession of the antibody with the required specific function of any monoclonal antibody which recognizes the conformation of the amino acid sequence of SEQ ID NO:12 of PIVKA-II. However, as discussed above, without any way to determine how broad the genus of such antibodies are, there is no way to determine if these antibodies represent the full breadth of what is claimed. Moreover, it appears from the disclosure that these antibodies bind 35-45aa of PIVKA-II, whereas the claims are drawn to any monoclonal antibody which recognizes the conformation of the amino acid sequence of SEQ ID NO:12. The disclosure of these specific antibodies would not convey to the artisan that Applicant was in possession of the full genus of all antibodies which possess the required functions nor does it allow the skilled artisan to envisage the specific structure of such antibodies.
Further note the decision in Amgen v. Sanofi 2017, where the Court supported previous decisions (Centocor 2011; Abbvie 2014) that defining an antibody solely by what it binds does not satisfy the written description requirement, stating that this would allow patentees to “claim antibodies by describing something that is not the invention, i.e., the antigen”. This decision has precipitated guidance to the Office instructing that the portion of MPEP 2163 regarding the “newly characterized antigen test” (indicating a well-characterized antigen is sufficient to satisfy written description for antibodies which bind that antigen) should no longer be used and that contrary materials should not be relied upon as reflecting the current state of the law.
Applicant has not described the claimed invention sufficiently to show they had possession of the claimed genus of anti-tau human monoclonal antibodies or human antibodies. Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rochester v. G.D. Searle & Co., 358 F.3d 916, 69 USPQ2d 1886 (Fed. Cir. 2004).
Further, the Federal Circuit has clarified Written Description as it applies to antibodies in the recent decision Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017). The Federal Circuit explained in Amgen that when an antibody is claimed, 35 U.S.C. 112(a) (or pre-AIA first paragraph) requires adequate written description of the antibody itself. Amgen, 872 F.3d at 1378-79. The Amgen court expressly stated that the so-called “newly characterized antigen” test, which had been based on an example in USPTO-issued training materials and was noted in dicta in several earlier Federal Circuit decisions, should not be used in determining whether there is adequate written description under 35 U.S.C. 112(a) for a claim drawn to an antibody. Citing its decision in Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., the court 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. Amgen, 872 F.3d at 1378-79, quoting Ariad, 598 F.3d 1336, 1345 (Fed. Cir. 2010). In view of the Amgen decision, adequate written description of a newly characterized antigen alone is not considered adequate written description of a claimed binding molecule or antibody to that antigen, even when preparation of such an antibody is routine and conventional. Id.
The limited amount of demonstrated species for the claimed genus of antibodies do not represent the astronomical and potentially unknowable breadth of all possible amino acid sequences which will result in the desired binding or functional properties of the claimed antibodies. This is exemplified by the Court decision in Abbvie (Abbvie v Janssen, 759 F.3d 1285 (Fed. Cir. 2014)), where Abbvie developed over 200 antibodies that shared 99.5% identity in the variable regions and which bound the target, but in no way allowed one to envisage the unique structure of a competitor’s (Centocor) antibodies which bound the same target but shared only 50% sequence similarity. Additionally, as noted in Amgen, knowledge that an antibody binds to a particular epitope on an antigen tells one nothing at all about the structure of the antibody, wherein “instead of analogizing the antibody-antigen relationship to a ‘key in a lock,’ it [is] more apt to analogize it to a lock and ‘a ring with a million keys on it.” (Internal citations omitted, emphasis in original). Therefore, those of skill in the art would not accept a disclosure of the limited antibodies as evidence that the inventor had been in possession of the genus of functionally-recited antibodies presently claimed.
Therefore, claims 1-2, 7 and 13 do not meet the written description requirement.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-4 and 8-10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gangadharan et al., US2010/0291602 (IDS 5/27/2022).
Gangadharan teaches methods using sandwich ELISA (see [0135]) as required in instant claims 1-2 and 8. Gangadharan teaches that in this type of assay, one antibody is bound to the bottom of a plate well; the antigen, a biomarker protein, is added and unbound products are removed by washing; a second, labeled antibody that binds to the antigen is then added and the amount of bound secondary antibody is quantified, usually colorimetrically (see [0116], [0135]) and reads on instant claims 1-4 and 8-11. Gangadharan teaches monoclonal antibodies that bin linear and conformational epitopes (see [0080]-[0084]) and reads on the requirements of instant claims 1-2 and 8.
Claims 1-5 and 8-11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yoshimura et al., US 2012/0020972 (IDS 5/27/2022).
Yoshimura teaches methods using sandwich ELISA to detect PIVKA-II (see [0123]-[0125] and claim 31) as required in instant claims 1-2, 5, 8 and 11. Yoshimura teaches using monoclonal antibodies and labeled antibodies to detect PIVKA-II protein (see [0125]; [0136]) as required in instant claims 4-5 and 10-11. Yoshimura teaches immobilizing the first antibody on a solid phase (see [0128]; [0136] and claim 30) and reads on instant claims 3 and 9. Yoshimura teaches that the epitopes that antibodies bind include linear and three dimensional (3D) structure characteristics (aka; conformational epitope; see [0058]) and reads on the limitations of instant claims 1-2, and 8.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. WO2012/002345 (instant PTO-892) is the English translation of the Japanese language patent application that teaches sandwich ELISA to detect PIVKA-II fragments like aa 34-46 of PIVKA-II in their SEQ ID NO: 9.
NO claims are allowed.
Advisory Information
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/AURORA M FONTAINHAS/Primary Examiner, Art Unit 1675
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