DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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.
Withdrawn Rejections
The 112a enablement rejection of the claims is withdrawn in response to the amendments. The claims no longer require determining the amount or concentration of the ISVD, they now recite broadly “analyzing a compound”. Furthermore, the capturing and detection agents now are limited by their “inability to bind the quencher with a greater affinity that 3 micromolar”, which is not limiting the agents to be capable of binding to the quencher as previously recited. These new embodiments render the claims enabled.
The rejection of claims 2 and 9 under 112(b) are withdrawn in response to the amendments.
Priority
Acknowledgment is made of the present application as a proper National Stage (371) entry of PCT Application No. PCT/EP2017/065219, filed 06/21/2017, which claims benefit under 35 U.S.C. 119(e) to provisional application No. 62/353,784, filed 06/23/2016.
Status of the Claims
Claims 1-14 are pending; claims 1-3, 7 and 9-11 are amended; claims 13-14 are newly recited; no claims are withdrawn. Claims 1-14 are examined below.
Maintained Rejections
Claim Rejections - 35 USC § 112
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 1-12 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. This is a written description rejection.
Claim 1 and its dependent claims require a capturing agent and a detection agent that bind to an ISVD and that do not bind to a quencher with an affinity of greater than 3 micromolar. The specification does not describe which amino acid residues, nucleic acid residues, or other molecular components are present in the genus of agents encompassed by claims 1-12. The specification fails to disclose the structures common to all members of the genus and fails to provide sufficient specific examples of agents to be used. In the absence of a known or disclosed correlation between structure and function, claims which encompass variants defined by their function are generally not considered described. Applicant is directed to MPEP § 2163 for guidelines on compliance with the written description requirement.
Regarding the claimed scope that includes the use of antibodies, 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 an antigen alone is not considered adequate written description of a claimed antibody to that antigen, even when preparation of such an antibody is routine and conventional. Id.
Functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. Abbvie Deutschland GMBH & Co. v. Janssen Biotech, Inc. (759 F.3d 1285 (Fed. Cir. 2014). “When a patent claims a genus using functional language to define a desired result, the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus." Capon v. Eshhar, 418 F.3d 1349 (Fed. Cir. 2005).
Consequently, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the full genus of capture and detection agents encompassed by the claims.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111 (Fed. Cir. 1991), clearly states that “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).
The skilled artisan cannot envision the detailed chemical structure of each genus encompassed by the method claims, i.e., the capturing agent and the detection agent (compounds that bind to ISVD, or a protein or polypeptide that comprise at least one ISVD), and the quencher, wherein the quencher is a protein or polypeptide that has
been selected based on its ability to be bound by pre-existing antibodies in the sample. Conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of identification. Adequate written description requires more than a mere statement that it is part of the invention. 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 (Fed. Cir. 1991). Therefore, the instant claims do not meet the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph.
New Rejections
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 13-14 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Baumeister et al. (WO 2012/175741 A2)-Cited on IDS 5/7/2025 ("Baumeister") .
Regarding claims 13-14, Baumeister teaches a method for analyzing a compound in a sample, wherein the compound is an immunoglobulin single variable domain (ISVD) having a C-terminal extension or one or more framework mutations that reduce binding by pre-existing antibodies, or a protein or polypeptide that comprises the ISVD at its C-terminal end (“assays for analyzing biological samples from people that are treated with ISV's” page 1 lines 20-21, “To better understand the invention described herein, it should already be noted that-by contrast - in the methods that are used herein to predict whether an ISV will give rise to protein interference, the ISV will usually be used as the "antigen" (i.e., as the compound to be detected)” page 2 lines 22-25, “By contrast, the present invention provides methods and assays that easily allow the skilled person to predict whether an immunoglobulin single variable domain will or will not have a tendency to undergo aspecific protein interference in an ADA assay…The present invention also describes a number of modifications that can be made to variable domains in order to reduce or essentially avoid such protein interference. According to one non-limiting aspect, this modification involves adding a limited number (as further described herein) of amino acid residues (as further described herein) to the C-terminal end of the variable domain” page 4 lines 1-3 and 9-13), and wherein the sample comprises pre-existing antibodies (“the invention can be used to predict, avoid or reduce such protein interference (and/or aspecific signals usually associated with the same) in biological samples (i.e., "test samples") obtained from a subject to whom one or more such ISV' s or Nano bodies ( or an ISV -based biological or Nanobody-based biological, as further defined herein) have been administered, wherein said samples as suitable for and/or intended for use in an immunological assay, such as an ADA assay. As mentioned, such a biological sample may be blood (including whole blood, serum or plasma)” page 17 lines 4-10), which method comprises: a) selecting: a quencher, wherein the quencher is an ISVD that has an exposed C-terminal end or lacks the one or more framework mutations that reduce binding by pre-existing antibodies, or a protein that comprises, at its C-terminal end, an ISVD that has an exposed C-terminal end (“the ISV that is coated on the plate” page 3 lines 2-3); a capturing agent, wherein the capturing agent is an immunoglobulin that is capable of binding to the compound, a polypeptide or construct that comprises an immunoglobulin that is capable of binding to the compound, or a target that is bound by the compound (“an antibody (which is as further described herein) is used as the "analytical agent" (i.e., as a means to detect whether a given ISV binds or not, respectively; and thus has a high or increased risk of giving rise to protein interference or not, respectively… also referred to herein as the "analytical antibody"” page 2 lines 25-29); and a detection agent, wherein the detection agent is an immunoglobulin that is capable of binding to the compound, a polypeptide or construct that comprises an immunoglobulin that is capable of binding to the compound, or a target that is bound by the compound (“As shown for instance in Figure 1” page 2 line 33, see Figure 1 showing the detection agent “Nb-SULFO”); b) contacting the sample with the capturing agent in the presence of the quencher, wherein the contacting is performed under conditions selected such that the capturing agent binds the compound in the sample (page 3 lines 2-3, “contacting said ISV or Nanobody (or ISV-based or Nanobody-based drug) with an antibody that has been obtained from a human subject and that has been selected, generated and/or isolated based on its ability to recognize and/or bind to the C-terminal end of an ISV or Nanobody (the "analytical antibody");” page 8 lines 4-7); and d) measuring a signal corresponding to the amount of detection agent bound to the compound bound by the capturing agent (“determining whether said ISV or Nanobody (or ISV-based or Nanobody-based drug) is bound by said antibody in said immunoassay” page 8 lines 8-9, “The skilled person will also be familiar with a number of different commercially available technology platforms that have been shown to be suitable for setting up and performing ADA assays. These include but are not limited to the MSD platform… Some non-limiting examples of ADA assay formats are also schematically shown in Figures lA to 1 C.” page 2 lines 10-15, “the specific bridging assay described in the Examples (which is a competitive assay) the analytical antibody is still used as the analytical agent (i.e., to determine whether the ISV of interest binds or not, respectively; and thus has a high or increased risk of giving rise to protein interference or not, respectively)” page 3 lines 3-6, “reading the ECL units (ECLU) on an MSD instrument (Sector Imager 2400 reader)” page 67 line 27).
Response to Arguments
Applicant's arguments filed 7/22/2026 have been fully considered but they are not persuasive.
Regarding the 112a written description rejection,
Applicant argues that “Here, the claims recite a method in which a capture agent, a detection agent, and a quencher are selected as active steps. The claims are not composition claims…The Examiner's written description analysis of the claims is inconsistent with established case law and M.P.E.P. guidance (which require an analysis of the claimed invention). The written description requirement does not require that the application demonstrate the inventors were in possession of the full scope of compositions selected ( or arrived at) while performing a claimed method. For example, under the Examiner's logic, to establish written description of a claim to a method of treating a subject having a disease (a characteristic of a subject without a corresponding structure), one would need to demonstrate that the inventors were in possession of
the full genus of subjects having the disease - which is clearly not required. Again, the Examiner has not established that one having ordinary skill in the art would not reasonably conclude that the inventors were in possession of a method that comprises an active step of selecting a capture agent, a detection agent, and a quencher and the use thereof in a method for analyzing a compound in a sample (i.e., what is claimed)” (page 7 para. 4 and page 8 paras. 2-3).
However, even though the claims are method claims (not product claims), the claims still require the selection and use of the claimed reagents, which are recited in terms of their function (“a quencher, wherein the quencher is a protein or polypeptide that is selected based on an ability to be bound by pre-existing antibodies in the sample; a capturing agent, wherein the capturing agent is selected based on an ability to bind the compound and on an inability to bind the quencher with a greater affinity than 3 micromolar (µM); and a detection agent wherein the detection agent is selected based on an ability to bind the compound and on an inability to bind the quencher with a greater affinity than 3 micromolar (µM)”). Therefore, in order to show possession of the genus of agents that are encompassed by the claims, the specification must also describe the structure of such agents. Given that the specification fails to provide sufficient written description of the structure of the claimed reagents, the claims remain rejected under 112a written description. The arguments are not persuasive.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FERNANDO IVICH whose telephone number is (703)756-5386. The examiner can normally be reached M-F 9:30-6:00 (E.T.).
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/Fernando Ivich/Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
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