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 .
Applicant’s response filed on 2/2/2026 is acknowledged.
Election/Restrictions
Claims 1-20 are pending.
Applicant’s election without traverse of Group I, claims 1-8 and 20, directed towards an epitope binding agent or conjugate thereof that specifically binds to Cystinosin in the reply filed on 2/2/2026 is acknowledged.
Claims 9-19 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 2/2/2026.
Claims 1-8 and 20 are currently under consideration for their full scope.
Claim Rejections - 35 USC § 112
Written Description
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 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.
Applicant is in possession of: epitope binding agents or conjugates which specifically bind to Cystinosin and which comprise the 6 CDRs of SEQ ID NOs: 1, 2, 3, 7, 8, and 9 and VH and VL domains of SEQ ID NOs:13 and 14, respectively, including the disclosed IgG-3H5 antibody and a kit comprising these antibodies.
Applicant is not in possession of: epitope binding agents or conjugates which bind cystinosin that comprise variants (i.e. at least 80% identity) of the 6 CDRs of SEQ ID NOs: 1, 2, 3, 7, 8, and 9 and variants (i.e. at least 70% identity) of the VH and VL domains of SEQ ID NOs:13-14 and a kit comprising these antibodies.
The claims encompass antibodies with variants of the recited amino acid sequences. The claims recite variable region sequences containing amino acids not found in the IgG-3H5 that was actually produced in the specification which actually binds Cystinosin. The skilled artisan cannot envision all the antibody and kit possibilities recited in the instant claims.
Consequently, conception cannot be achieved until a representative description of the structural and functional properties of the claimed invention has occurred, regardless of the complexity or simplicity of the method.
The specification must set forth the structural features that allow one of ordinary skill in the art to identify and produce the recited antibodies. In the instant case, definition by function does not suffice to define the genus because it is only an indication of what the antibodies do, rather than what they are.
It is well established in the art that it is highly unpredictable which changes in amino acid sequence can be made in complementarity determining regions (CDRs) of a parental antibody such that the derived antibody retains the binding specificity and affinity of the parent antibody. The art of Mariuzza et al. (PTO-892; page 1, Reference X) reviews the structural basis of antigen-antibody recognition and teaches that a naturally occurring antibody comprises light and heavy chains. The antigen-combining site of an antibody is a three-dimensional structure, which fully comprises six "complementarity-determining regions" (CDRs), three each from the light and heavy chains. The amino acid sequences of the CDRs are hypervariable, as the amino acid residues contained within the CDRs determine much of antibody's antigen-binding specificity. Of the amino acid residues of the antibody contacting the antigen, six are within the light chain, nine are within the heavy chain, and two are within the constant or nearly constant "framework" regions (In particular, whole document). As such, one of skill in the art would not know which of the recited antibody variants would have the claimed function of binding to Cystinosin because it is the 6 CDRs together which determine the antibody's antigen-binding specificity.
It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites. MacCallum, et al. (PT0-892; page 1, Reference W) analyzed many different antibodies for interactions with antigen and state that although CDR3 of the heavy and light chain dominate, a number of residues outside the standard CDR definitions make antigen contacts (see page 733, right column) and non-contacting residues within the CDRs coincide with residues as important in defining canonical backbone conformations (see page 735, left column). De Pascalis, et al. (PTO-892; page 1, Reference U) demonstrate that grafting of the CDRs into a human framework was performed by grafting CDR residues and maintaining framework residues that were deemed essential for preserving the structural integrity of the antigen binding site (see page 3079, right column). Although abbreviated CDR residues were used in the constructs, some residues in all 6 CDRs were used for the constructs (see page 3080, left column). Thus, it is unpredictable as to what amino acids can be changed in the original intact antibodies disclosed in the specification wherein the antibodies would still function. Thus, the skilled artisan cannot envision the detailed structure of the encompassed invention and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation.
It is well established in the art that the formation of an intact antigen-binding site generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs which provide the majority of the contact residues for the binding of the antibody to its target epitope. The amino acid sequences and conformations of each of the heavy and light chain CD Rs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites. Even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function.
As evidenced by the art of Goel et al. (PTO-892; page 1, Reference V), Khan et al. (PTO-892; Page 2; Reference V) and Poosarla et al. (PTO-892; Page 2; Reference W), antibody specificity for a particular antigen does not correlate with any particular structure for the antibodies themselves. It was well known to those skilled in the art at the time the invention was made that minor structural differences among structurally related antibodies or compositions thereof could result in substantially different binding activities. Given the lack of guidance in the specification, it is unpredictable which antibodies with which structures would exhibit the recited functions. The specification does not disclose a correlation between the structure of the antibodies themselves and their function of binding cystinosin such that a skilled artisan would have known what antibody structures possess the claimed functions.
As evidenced by Stull et al (PTO-892; page 1, Reference N), there is an antibody that specifically binds to mouse DLL3 with a VH region (Reference SEQ ID NO:155) 81.2% sequence identical to instant SEQ ID NO:13 and a VL region (Reference SEQ ID NO:162) 90.7% sequence identical to instant SEQ ID NO:14. As evidenced by Zhu et al (PTO-892; page 1, Reference B), there is an antibody that specifically binds to CLDN18.2 with a VH region (Reference SEQ ID NO:10) 80.2% sequence identical to instant VH region of SEQ ID NO:13 and comprises 90% sequence identity to instant CDR-H1 of SEQ ID NO:1 and a VL region (Reference SEQ ID NO:12) 89.4% sequence identical to instant VL region of SEQ ID NO:14 and comprises 88.89% sequence identity to instant CDR-L2 of SEQ ID NO:8. Therefore, as the claims are written, there is little to no correlation between the recited structure of the claimed antibody and the recited function of specifically binding to Cystinosin.
The specification does not disclose a correlation between the antibody structure and the function of binding cystinosin such that a skilled artisan would have known what antibody variants possess the claimed function. "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" Ex parte Kubin (83 U.S.P.Q.2d 1410 (BPAI 2007)), at page 16. In this instant case, Applicants have not provided the requisite identifying structural features of the antibodies encompassed. "Without a correlation between structure and function, the claim does little more than define the claimed invention by function" supra, at page 17.
U.S. Court of Appeals for the Federal Circuit recently decided Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017) which concerned adequate written description for claims drawn to antibodies. The Federal Circuit explained in Amgen that when an antibody is claimed, 35 U.S.C. § l 12(a) 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. § l 12(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 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. Id.
The specification does not provide adequate written description of the claimed invention. The legal standard for sufficiency of a patent's (or a specification's) written description is whether that description "reasonably conveys to the artisan that the inventor had possession at that time of the ... claimed subject matter", Vas-Cath, Inc. V. Mahurkar, 19 U.S.P.Q.2d 1111 (Fed. Cir. 1991). In the instant case, the specification does not convey to the artisan that the applicant had possession at the time of invention of the claimed invention.
Adequate written description requires more than a mere statement that it is part of the invention and a reference to a potential method of isolating it. In the instant application, the amino acid sequence itself or isolated protein is required. See Fiers v. Revel, 25 USPQ 2d 1601 at 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Lts., 18 USPQ2d 1016. In view of the aforementioned problems regarding description of the claimed invention, the specification does not provide an adequate written description of the invention claimed herein. See The Regents of the University of California v. Eli Lilly and Company, 43 USPQ2d 1398, 1404-7 (Fed. Cir. 1997). In University of California v. Eli Lilly and Co., 39 U.S.P.Q.2d 1225 (Fed. Cir. 1995) the inventors claimed a genus of DNA species encoding insulin in different vertebrates or mammals, but had only described a single species of cDNA which encoded rat insulin. The court held that only the nucleic acids species described in the specification (i.e. nucleic acids encoding rat insulin) met the description requirement and that the inventors were not entitled to a claim encompassing a genus of nucleic acids encoding insulin from other vertebrates, mammals or humans, id. at 1240. The Federal Circuit has held that if an inventor is "unable to envision the detailed constitution of a gene so as to distinguish it from other materials . . . conception has not been achieved until reduction to practice has occurred", Amgen, Inc. v. Chugai Pharmaceutical Co, Ltd., 18 U.S.P.Q.2d 016 (Fed. Cir. 1991). Attention is also directed to the decision of The Regents of the University of California v. Eli Lilly and Company (CAFC, July 1997) wherein is stated: "The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 222 USPQ 369, 372-373 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[ e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate."). Accordingly, naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material. Thus, as we have previously held, a cDNA is not defined or described by the mere name "cDNA," even if accompanied by the name of the protein that it encodes, but requires a kind of specificity usually achieved by means of the recitation of the sequence of nucleotides that make up the cDNA." See Fiers, 984 F.2d at 1171, 25 USPQ2d at 1606.
As such, there is insufficient written description of the required kind of structure identifying information about the corresponding makeup of the claimed antibodies to demonstrate possession.
Enablement
Claims 1, 3-8, and 20 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.
Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized In re Wands (858 F2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)). The factors most relevant to this rejection are the scope of the claim, the amount of direction or guidance provided, the lack of sufficient working examples, the unpredictability in the art and the amount of experimentation required to enable one of skill in the art to practice the claimed invention.
While being enabled for: epitope binding agents or conjugates which specifically binds to Cystinosin and which comprise the 6 CDRs of SEQ ID NOs: 1, 2, 3, 7, 8, and 9 and VH and VL domains of SEQ ID NOs:13 and 14, respectively, including the disclosed IgG-3H5 antibody and a kit comprising these antibodies.
the specification does not reasonably provide enablement for: epitope binding agents or conjugates which specifically binds cystinosin that comprise variants (i.e. at least 80% identity) of the 6 CDRs of SEQ ID NOs: 1, 2, 3, 7, 8, and 9 and variants (i.e. at least 70% identity) of the VH and VL domains of SEQ ID NOs:13-14 and a kit comprising these antibodies.
The breadth of claims 1, 3-8, and 20 encompass antibodies with variants of the recited amino acid sequences and amino acid variations not found in IgG 3H5 antibody. The breadth of claims 1, 3-8, and 20 encompass any antibody that is at least 80% identical to one or more of SEQ ID NOs:1, 2, or 3 and one ore more of SEQ ID NOs:7, 8, or 9 and any antibody that is at least 70% identical to SEQ ID NOs:13 and 14.
The specification (page 11, [0051]) describes an epitope binding agent that binds an antigen of interest with sufficient affinity such that the antibody/epitope binding agent is useful as an assay reagent and typically does not significantly cross-react with other polypeptides. Additionally, the specification (pages 36-37, [0134]-[0135], Example 2) describes the epitope binding agent that specifically binds Cystinosin to be IgG-3H5, a mouse monoclonal anti-human Cystinosin antibody, that was prepared from the hybridoma designed IgG-3H5 (subclass IgG1) with a heavy chain variable region comprising CDR-H1, -H2, and -H3 of SEQ ID NOs:1-3, respectively, further shown in SEQ ID NO:13 and a light chain variable region comprising CDR-L1, -L2, and -L3 of SEQ ID NOs:7-9, respectively, further shown in SEQ ID NO:14.
It is well established in the art that it is highly unpredictable which changes in
amino acid sequence can be made in binding structures such that the derived
polypeptide retains the ability to bind. Sailer et al. (PTO-892; page 2, Reference U)
teaches that “"proteins exist as ensembles of similar conformations. The effect of a
mutation depends on the relative probabilities of conformations in the ensemble, which
in turn, depend on the exact amino acid sequence of the protein. Accumulating substitutions alter the relative probabilities of conformations, thereby changing the
effects of future mutations. This manifests itself as subtle but pervasive high-order
epistasis. Uncertainty in the effect of each mutation accumulates and undermines
prediction. Because conformational ensembles are an inevitable feature of proteins, this
is likely universal" (Sailer; abstract, whole document); and that "a key point from our
work is that unpredictability can arise even in this extraordinary simple system. The
problem of predicting evolution will only become harder as the complexity and realism of
the models increase. Using a larger protein, for example, would increase the number of
possible options and degeneracy of trajectories, making predictions more challenging."
(Sailer; page 11942, left column, whole document).
One of ordinary skill in the art could not predict which amino acids within the full-
length amino acid sequences of the recited genus of antibodies could be
substituted for which amino acids and whether the resulting polypeptide combinations
exhibits binding. Predicting polypeptide structure from sequence data of a single amino
acid sequence and attempting to utilize the predicted structural determinations to
ascertain binding or functional aspects of any protein and what changes can be
tolerated with respect thereto is complex and well outside the realm of routine
experimentation. In re Fisher indicates that the more unpredictable an area is, the more
specific enablement is necessary in order to satisfy the statute, 427 F.2d 833, 839, 166
USPQ 18, 24 (CCPA 1970).
As evidenced by Stull et al (PTO-892; page 1, Reference N), there is an antibody that specifically binds to mouse DLL3 with a VH region (Reference SEQ ID NO:155) 81.2% sequence identical to instant SEQ ID NO:13 and a VL region (Reference SEQ ID NO:162) 90.7% sequence identical to instant SEQ ID NO:14. As evidenced by Zhu et al (PTO-892; page 1, Reference B), there is an antibody that specifically binds to CLDN18.2 with a VH region (Reference SEQ ID NO:10) 80.2% sequence identical to instant VH region of SEQ ID NO:13 and comprises 90% sequence identity to instant CDR-H1 of SEQ ID NO:1 and a VL region (Reference SEQ ID NO:12) 89.4% sequence identical to instant VL region of SEQ ID NO:14 and comprises 88.89% sequence identity to instant CDR-L2 of SEQ ID NO:8. Therefore, it is unpredictable whether antibodies with either 80% identity to the 6 CDRs and 70% identity to the VH and VL regions will perform the recited function of specifically binding to Cystinosin and it is unpredictable which amino acids are important for preserving the recited function of specifically binding to Cystinosin.
As such the claims are not enabled for the genus of antibodies that specifically bind to Cystinosin comprising one or more of heavy chain variable region CDRs of SEQ ID NOs:1-3 with 80% sequence identity, one or more of light chain variable region CDRs of SEQ ID NOs:7-9 with 80% sequence identity, and a heavy and light chain variable region of SEQ ID NOs:13 and 14 with 70% sequence identity. One of ordinary skill in the art cannot use antibodies with unpredictable functions. One of ordinary skill in the art would be required to practice undue experimentation to practice the invention commensurate in scope with the claims.
In view of the quantity of experimentation necessary, the lack of working examples, the unpredictability in the art, the lack of sufficient guidance in the
specification, and the breadth of the claims, it would take undue trials and errors to
make and use the encompassed antibody with 80% identity to one or more of heavy chain variable region CDRs of SEQ ID NOs:1-3, 80% identity to one or more of light chain variable region CDRs of SEQ ID NOs:7-9, and 70% identity to VH and VL domains of SEQ ID NOs:13 and 14 recited in the claims for predictable function to specifically bind Cystinosin.
Reasonable correlation must exist between the scope of the claims and scope of
the enablement set forth. In view of experimentation necessary the limited working
examples, the nature of the invention, the state of the prior art, the unpredictability of the
art and the breadth of the claims, it would take undue trials and errors to practice the
claimed invention.
Priority
This application claims domestic priority to U.S. Provisional Application 63/366,972 effectively filed on 06/24/2022.
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 1 and 3-6 is/are rejected under 35 U.S.C. 102(a)(2) as being unpatentable by U.S. Patent Application Publication US 2025/0382364 A1 (PTO-892; page 1, Reference B; "Alteber") as evidenced by the attached sequence alignment.
Alteber teaches methods of treating cancer comprising administering an anti-TIGIT antibody alone or in combination with an anti-PVRIG antibody (Alteber; Abstract; [0018]). Alteber teaches TIGIT as an attractive target for monoclonal antibody therapy and disease treatment as TIGIT is highly expressed on lymphocytes and the TIGIT-PVR axis may be a dominant immune escape mechanism for cancer (Alteber; [0014-0015]). Alteber additionally teaches thirteen anti-TIGIT antibodies including CHA.9.546.1, CHA.9.547.1, CHA.9.547.2, CHA.9.547.3, CHA.9.547.4, CHA.9.547.6, CHA.9.547.7, CHA.9.547.8, CHA.9.547.9, CHA.9.547.10, CHA.9.547.11, CHA.9.547.12, CHA.9.547.13, each antibody comprising an scFv variable heavy chain domain and a scFv variable light chain domain and one anti-CD226 antibody (i.e. DNAM antibody sequences) comprising scFv variable heavy chain domain of SEQ ID NO:1317 and scFv variable light chain domain of SEQ ID NOs:1322 (Alteber; Figures 13AB-AJ and 13AR-AU; Figure 24; [0161-0162]; [0216]-[0217]; [0401]; [0467]; see attached sequence alignment). The reference antibodies each contain three heavy chain CDRs, vhCDRs1-3 and three light chain CDRs, vlCDRs1-3 (Alteber; Figures 13AB-AJ and 13AR-AU; Figure 24; [0161-0162]; [0216]-[0217]; [0401]; [0467]; see attached sequence alignment).
Regarding claim 1, Alteber teaches an epitope binding agent or conjugate thereof, comprising: (a) a heavy chain variable region (VH) comprising one or more of a CDR-H1, CDR-H2, and CDR-H3 with at least 80% identity to the amino acid sequence set forth in SEQ ID NO: 1, 2 or 3; (b) a light chain variable region (VL) comprising one or more of a CDR-L1, CDR-L2, and CDR-L3 with at least 80% identity to the amino acid sequence set forth in SEQ ID NO: 7, 8 or 9; or both:
Reference anti-CD226 antibody (i.e. DNAM Antibody Sequences) contains a VH domain of reference SEQ ID NO:1317 which contains instant SEQ ID NO:1 with one amino acid difference (8/9 amino acids, 88.9% sequence identity), instant SEQ ID NO:2 with four amino acid differences (8/12 amino acids, 66.67% sequence identity), and instant SEQ ID NO:3 with five amino acid differences (5/9 amino acids, 55.6% sequence identity); and a VL domain of SEQ ID NO:1322 which contains instant SEQ ID NO:7 with four amino acid differences (7/11 amino acids, 63.6% sequence identity), instant SEQ ID NO:8 with four amino acid differences (5/9 amino acids, 55.6% sequence identity), and instant SEQ ID NO:9 with seven amino acid differences (3/10 amino acids, 30% sequence identity) (Alteber; Figure 24; see attached sequence alignment);
Reference antibody CHA.9.546.1 contains a VH domain of reference SEQ ID NO:1087 which contains instant SEQ ID NO:1 with two amino acid difference (8/10, 80% sequence identity), instant SEQ ID NO:2 with four amino acid difference (8/12, 66.67% sequence identity), instant SEQ ID NO:3 with five amino acid difference (5/10, 50% sequence identity); and a VL domain of SEQ ID NO:1092 which contains instant SEQ ID NO:7 with two amino acid difference (9/11, 81.2% sequence identity), instant SEQ ID NO:8 with one amino acid difference (8/9, 88.9% sequence identity), and instant SEQ ID NO:9 with three amino acid difference (7/10, 70% sequence identity) (Alteber; Figure 13AB; see attached sequence alignment);
Reference antibody CHA.9.547.1 contains a VH domain of reference SEQ ID NO:1097 which further contains instant SEQ ID NO:1 with two amino acid difference (8/10, 80% sequence identity), instant SEQ ID NO:2 with four amino acid difference (8/12, 66.67% sequence identity), instant SEQ ID NO:3 with six amino acid difference (4/10, 40% sequence identity); and a VL domain of SEQ ID NO:1102 which contains instant SEQ ID NO:7 with two amino acid difference (9/11, 81.2% sequence identity), instant SEQ ID NO:8 with one amino acid difference (8/9, 88.9% sequence identity), and instant SEQ ID NO:9 with three amino acid difference (7/10, 70% sequence identity) (Alteber; Figure 13AC; see attached sequence alignment);
Reference antibody CHA.9.547.2 contains a VH domain of reference SEQ ID NO:1107 which further contains instant SEQ ID NO:1 with two amino acid difference (8/10, 80% sequence identity), instant SEQ ID NO:2 with three amino acid difference (9/12, 75% sequence identity), instant SEQ ID NO:3 with eight amino acid difference (2/10, 20% sequence identity); and a VL domain of SEQ ID NO:1112 which contains instant SEQ ID NO:7 with two amino acid difference (9/11, 81.2% sequence identity), instant SEQ ID NO:8 with one amino acid difference (8/9, 88.9% sequence identity), and instant SEQ ID NO:9 with three amino acid difference (7/10, 70% sequence identity) (Alteber; Figure 13AD; see attached sequence alignment);
Reference antibody CHA.9.547.12 contains a VH domain of reference SEQ ID NO:1267 which further contains instant SEQ ID NO:1 with two amino acid difference (8/10, 80% sequence identity), instant SEQ ID NO:2 with three amino acid difference (9/12, 75% sequence identity), instant SEQ ID NO:3 with eight amino acid difference (2/10, 20% sequence identity); and a VL domain of SEQ ID NO:1272 which contains instant SEQ ID NO:7 with two amino acid difference (9/11, 81.2% sequence identity), instant SEQ ID NO:8 with three amino acid difference (6/9, 66.7% sequence identity), and instant SEQ ID NO:9 with three amino acid difference (7/10, 70% sequence identity) (Alteber; Figure 13AT; see attached sequence alignment);
See the attached sequence alignment for the other reference antibodies CHA.9.547.3, CHA.9.547.4, CHA.9.547.6, CHA.9.547.7, CHA.9.547.8, CHA.9.547.9, CHA.9.547.10, CHA.9.547.11, and CHA.9.547.13 taught by Alteber (Alteber; Figures 13AE-AJ, 13AR-AS, and 13AU). It is noted that Alteber does not teach the functional language of the epitope binding agent specifically binding Cystinosin.
Regarding claim 3, Alteber teaches wherein the VH comprises an amino acid sequence comprising at least 70% identity to the amino acid sequence set forth in SEQ ID NO: 13:
Reference VH of SEQ ID NO:1317 is 72.2% sequence identical to instant SEQ ID NO:13 (see attached sequence alignment, page 1);
Reference VH of SEQ ID NO:1087 is 72.3% sequence identical to instant SEQ ID NO:13 (see attached sequence alignment, page 1);
Reference VH of SEQ ID NO:1097 is 71.8% sequence identical to instant SEQ ID NO:13 (see attached sequence alignment, page 2);
Reference VH of SEQ ID NO:1107 is 72.3% sequence identical to instant SEQ ID NO:13 (see attached sequence alignment, page 3);
Reference VH of SEQ ID NO:1267 is 72.3% sequence identical to instant SEQ ID NO:13 (see attached sequence alignment, page 3).
See the attached sequence alignment for the other reference VH regions of CHA.9.547.3, CHA.9.547.4, CHA.9.547.6, CHA.9.547.7, CHA.9.547.8, CHA.9.547.9, CHA.9.547.10, CHA.9.547.11, and CHA.9.547.13 taught by Alteber (Alteber; Figures 13AE-AJ, 13AR-AS, and 13AU).
Regarding claim 4, Alteber teaches wherein the VL comprises an amino acid sequence comprises at least 70% identity to the amino acid sequence set forth in SEQ ID NO: 14:
Reference VL of SEQ ID NO:1322 is 70.2% sequence identical to instant SEQ ID NO:14 (see attached sequence alignment, page 1);
Reference VL of SEQ ID NO:1092 is 86.5% sequence identical to instant SEQ ID NO:14 (see attached sequence alignment, page 2);
Reference VL of SEQ ID NO:1102 is 86.5% sequence identical to instant SEQ ID NO:14 (see attached sequence alignment, page 2);
Reference VL of SEQ ID NO:1112 is 86.5% sequence identical to instant SEQ ID NO:14 (see attached sequence alignment, pages 3);
Reference VL of SEQ ID NO:1272 is 84.5% sequence identical to instant SEQ ID NO:14 (see attached sequence alignment, page 4).
See the attached sequence alignment for the other reference VH regions of CHA.9.547.3, CHA.9.547.4, CHA.9.547.6, CHA.9.547.7, CHA.9.547.8, CHA.9.547.9, CHA.9.547.10, CHA.9.547.11, and CHA.9.547.13 taught by Alteber (Alteber; Figures 13AE-AJ, 13AR-AS, and 13AU).
Regarding claim 5, Alteber teaches wherein the epitope binding agent is an antibody (Alteber; Abstract; [0018]).
Regarding claim 6, Alteber teaches wherein the antibody is selected from the group consisting of: a monoclonal antibody, an lgG, Fv, single chain antibody, nanobody, diabody, scFv, Fab, F(ab')2, and Fab (Alteber; Abstract; [0018]; [0401]).
Claims 1 and 3-6 are included in this rejection because although Alteber is silent about the reference antibody binding to Cystinosin, the reference peptide is the same as the claimed peptide. Applicant is reminded that no more of the reference is required than that it sets forth the substance of the invention. The claimed functional limitations would be inherent properties of the referenced sequences. Products of identical chemical composition cannot have mutually exclusive properties. A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). See MPEP 2112.01.
The reference teachings anticipate the claimed invention.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 7-8 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent Application Publication US 2025/0382364 A1 (PTO-892; page 1, Reference B; "Alteber") in view of US Patent 4,277,437 A (IDS Reference 17 U.S. Patents; "Maggio") as evidenced by the attached sequence alignment.
Alteber has been discussed above. Alteber differs from the claimed invention regards to instant claims 7-8 and 20 wherein the epitope binding agent further comprises a detection antibody; wherein the detection molecule comprises a fluorescent label, phosphorescent molecules, chemiluminescent molecules, chromophores, luminescent molecules, photoaffinity molecules, colored particles and/or ligands, such as biotin fluorescent dyes, electrochemiluminescence dyes, metal-chelate complexes or labels; and a kit comprising (a) the epitope binding agent of claim 1, (b) reagents, and (c) instructions for use.
Maggio teaches a competitive protein binding method for determining the presence and concentration of an analyte where the assay is predicated on the presence of an analyte in an assay medium affecting the degree to which a chemiluminescence source is quenched by energy transfer to a quencher where the chemiluminescent source and quencher is conjugated to either the ligand or the receptor (i.e. an antibody) (Maggio; Abstract; (11); (15); (26); (364)). Maggio additionally teaches a kit comprising the critical reagents and ancillary material provided in relative proportions to obtain reproducible results and optimize the sensitivity of the assay (Maggio; (13); (366)-(368)).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date, to conjugate the antibody of Alteber with the chemiluminescence molecule or quencher of Maggio with reasonable expectation of success.
One of ordinary skill in the art would have been motivated to conjugate the antibody of Alteber with the chemiluminescence molecule or quencher of Maggio to determine the presence and concentration of an analyte within an assay medium.
Therefore, it would have been obvious to a person of ordinary skill in the art to conjugate the antibody of Alteber with the chemiluminescence molecule or quencher of Maggio to yield predictable results of chemiluminescent antibody capable of binding its target and emit energy to determine the presence and concentration of the antibody’s target.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date, to combine the antibody of Alteber with the kit of Maggio with reasonable expectation of success.
One of ordinary skill in the art would have been motivated to combine the antibody of Alteber with the kit of Maggio to use the antibody and other required reagents provided in relative proportions to optimize the sensitivity of the assay and improve reproducible of the chemiluminescent assay to accurately determine the presence and concentration of a target analyte.
Therefore, it would have been obvious to a person of ordinary skill in the art to combine the antibody of Alteber with the kit of Maggio to accurately determine the presence and concentration of a target analyte.
The invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence on the contrary.
Allowable Subject Matter
Claim 2 objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LEAH ELIZABETH STEIN whose telephone number is (571) 272-0093. The examiner can normally be reached M-F 8-5:30 EST.
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/LEAH ELIZABETH STEIN/ Examiner, Art Unit 1641
/NORA M ROONEY/ Primary Examiner, Art Unit 1641