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
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-11 in the reply filed 09/12/2025 is acknowledged.
Claims 12-14 are withdrawn from consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions and species, there being no allowable generic or linking claims. Election was made in the reply filed 09/12/2025.
Claims 1-11 are now under consideration in the instant Office Action.
Withdrawn Rejections
Rejections of claims 1-11 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paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter are hereby withdrawn in view of amendments to the claims.
Rejections of claim 1 under 35 U.S.C. 102(a)(2) as being anticipated by Chupp et al. (US 2019/0062457 A1, in IDS filed 08/07/2023) are hereby withdrawn in view of amendments to the claims which now include a structure for the antibody that is not disclosed in the reference used.
Rejections of claims 1-11 under 35 U.S.C. 103 as being unpatentable over Chupp et al. (US 2019/0062457 A1, in IDS filed 08/07/2023), in view of Lu et al. (in IDS filed 08/07/2023), General Hospital Corporation (WO 2019/157533 A1, in IDS filed 08/07/2023, hereinafter “GHC”), and Wang et al. (WO 2018/0327501 A1, in IDS filed 08/07/2023) are hereby withdrawn in view of amendments to the claims which now include a structure for the antibody that is not disclosed in the references used.
New Rejections
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 1-11 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.
Instant claim 1 recites “one or more heavy chain complementarity determining regions (CDR)s… and one or more light chain CDRs…”. It is unclear how many, or which, of the twenty recited sequences are intended to be included in the bispecific antibody as recited by the instant claim language. The instant invention is described to be a bispecific antibody, but does not list out complete embodiments of the antibody comprising the twelve CDRs or four heavy and light chain variable region sequences that are necessary. The dependent claims fail to rectify this deficiency and thus are also rejected.
Instant claim 1 uses the transitional term “having the sequence”. This term is problematic because the recitation of these terms in instant claim 1 renders the claim unclear by what not defining what is encompassed by “having” the sequences. Applicant has not conveyed that they are in possession of all the antibodies that are included in the broad term “having the sequence”. It is not immediately clear whether open or closed claim language is intended, Crystal Semiconductor Corp. v. Trilech Microelectronics Int’l Inc., 246 F.3d 1336, 1348, 57 USPQ2d 1953, 1959 (Fed. Cir. 2001) (term “having” in transitional phrase "does not create a presumption that the body of the claim is open"); Regents of the Univ. of Cal. v. Eli Lilly & Co., 119 F.3d 1559, 1573, 43 USPQ2d 1398, 1410 (Fed. Cir. 1997) (in the context of a cDNA having a sequence coding for human PI, the term “having” still permitted inclusion of other moieties), see MPEP 2111.03. Applicant is encouraged to use transitional phrases “comprising of” or “consisting of” to define the scope of a claim with respect to what unrecited additional components, if any, are excluded from the scope of the claims. The dependent claims fail to rectify this deficiency and thus are also rejected.
The sequences SEQ ID NOs: 1-20 that are recited in instant claim 1 are referred to as heavy and light chain complementarity determining regions, but are listed in the instant specification on pages 36-37 as lengthier heavy and light chain variable region sequences. This inconsistency renders the scope of the claims unclear.
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 1-11 are rejected under 35 U.S.C. 103 as being unpatentable over Elias et al. (US 2019/0062457 A1, in IDS filed 08/07/2023), in view of Chupp et al. (US 2019/060675 A1, in instant PTO-892), in view of Lu et al. (in IDS filed 08/07/2023), General Hospital Corporation (WO 2019/157533 A1, in IDS filed 08/07/2023, hereinafter “GHC”), and Wang et al. (WO 2018/0327501 A1, in IDS filed 08/07/2023).
Elias et al. discloses chitinase 3-like-1 (CHI3L1) neutralizing antibodies as therapeutics, see paragraph 0535. Elias et al. also discloses that these neutralizing antibodies can be bivalent antibodies that detects and neutralizes chitinase 3-like-1 (CHI3L1), and the inhibitor of CHI3L1 and the inhibitor of an immune checkpoint protein are present in the same bivalent antibody reagent. In some embodiments of any of the aspects, the immune checkpoint protein is PD-1 or CTLA4, see paragraph 0024. Elias et al. discloses that their invention can be encompassed within a pharmaceutically acceptable formula, see paragraph 0009. This meets the limitations of instant claim 1 wherein the antibody is a bispecific antibody that detects and neutralizes CHI3L1 and CTLA4 and instant 10 wherein the antibody is in a pharmaceutically acceptable formula.
Elias et al. further describes the bivalent antibody reagent as “an antibody reagent that comprises a first antigen-binding domain which has binding specificity for a first target, and a second antigen-binding domain which has binding specificity for a second target, i.e., the agent has specificity for two targets, e.g., CHI3L1 and PD-1, or CHI3L1 and CTLA4”, see paragraph 0144. Elias et al. also teaches that in some embodiments, “the antibody or antigen-binding portion thereof is a fully human antibody. In some embodiments of any of the aspects, the antibody, antigen-binding portion thereof, is a humanized antibody or antibody reagent. In some embodiments of any of the aspects, the antibody, antigen-binding portion thereof, is a fully humanized antibody or antibody reagent”, see paragraph 0052. Elias et al. proposes the mechanism for creating this single chain variable fragment in paragraph 0047, wherein they disclose "making it possible to prepare them as a single protein chain in which the VL and VH regions combine in order to form monovalent molecules, known as single chain Fv, ScFv". This meets the limitations of instant claims 2-5 wherein the structure of the antibodies are disclosed in several forms consisting of scFv-CTLA4, ScFv-CHI3LI, CHI3LI-HC-CTLA4, and CHI3LI-LC-CTLA4.
However, Elias et al. does not teach the sequences for the bispecific antibody. Chupp et al. remedies this deficiency.
Chupp et al. teaches the selective inhibition of inflammation using an anti-YKL-40 antibody, see Abstract. YKL-40 is a member of the chitinase-like family of secreted proteins (CLPs) and “the best studied CLP is chitinase 3 -like 1 (CHI3L1) that encodes the human protein YKL-40 and the mouse orthologue Brp-39”, see page 2. Chupp et al. teaches that the antibody which specifically binds to human YKL-40 is contained within the VH sequences of SEQ ID NOs: 1-12 and the VL sequences of SEQ ID NOs: 13-20, which are 100% homology matches to instant SEQ ID NOs: 1-20 of the same numeric designations. This meets the limitations of instant claim 1 wherein the sequences for the bispecific antibody are disclosed.
Elias et al. and Chupp et al. do not expressly disclose a scFv attached to the backbone of an antibody. Lu et al. remedies this deficiency.
Lu et al. discloses a scFv attached to the backbone of an antibody, see page 214, col 2, para 14 wherein Lu et al. teaches “a scFv of the first specificity was genetically fused to the C-terminus of either the Ig light chain constant domain (CL) or the first constant domain of the heavy chain (CH1) of a Fab fragment of a second specificity, to form two polypeptides, VL-CL-scFv (or L-scFv) or VH-CH1-scFv (or Fd- scFv), respectively."). This meets the limitations of instant claims 2-5 wherein the structure of the antibodies are disclosed in several forms consisting of scFv-CTLA4, ScFv-CHI3LI, CHI3LI-HC-CTLA4, and CHI3LI-LC-CTLA4.
However, Elias et al., Chupp et al., and Lu et al. do not teach the bispecific antibody enhanced Jurkat T cell attachment to U87 cells. GHC remedies this deficiency.
GHC discloses bispecific antibodies with enhanced Jurkat T cell attachment to U87 cells, see page 63, lines 19-20 wherein “Jurkat, NFAT-Luciferase, reporter cells (Signosis) were transduced with different CAR constructs prior to coculture with tumor targets at an E:T ratio of 1:1 for 24 hours”. GHC also discloses that "the CAR T cells of the invention can be used to deliver otherwise toxic antibodies, e.g. , anti-CTLA4 or anti-CD25", see page 20, lines 2-3. This meets the limitations of instant claim 6.
Elias et al., Chupp et al., Lu et al., and GHC do not teach a bispecific antibody with the ability to enhance Jurkat T cells to induce lactate dehydrogenase (LDH) release and cell cytotoxicity responses in U87 cells. Wang et al. remedies this deficiency.
Wang et al. discloses a bispecific antibody with the enhanced ability of Jurkat T cell to induce lactate dehydrogenase, LDH, release and cell cytotoxicity responses in U87 cells, see paragraph 0250 wherein "CytoTox 96 Assay measures lactate dehydrogenase (LDH) quantitatively. LDH is a stable cytosolic enzyme that is released upon lysis of cells and is released in the same way as radioactive 51Cr is released. The supernatant with released LDH medium can be detected by a 30-minute coupled enzyme reaction in which LDH converts a tetrazolium salt (INT) to a red formazan. The amount of red product produced is proportional to the number of lysed cells". Wang et al. illustrates in Figure 9 an increase in cytotoxicity in U87 cells treated with a bispecific antibody. This meets the limitations of instant claim 6 wherein the bispecific antibody comprises Jurkat T cell attachments o U87 cells, instant claim 7 wherein the Jurkat cells enhanced the cytotoxic cell responses in U87 cells, instant claim 8 wherein the enhanced accumulation of granzyme is observed in Jurkat cells, instant claim 9 wherein the Jurkat T cells induce lactate dehydrogenase release, and instant claim 11 wherein the combination of treatments results in the treatment of cancer.
It would be obvious at the time of the instant invention to use the anti-CHI3L1 and anti-CTLA4 antibody compositions relating to combinatorial therapies for cancer taught by Elias et al., with the sequences taught by Chupp et al., with the teachings of Lu et al. which discloses VH-CH1-scFv fusion proteins, and the anti-CTLA-4 transduced Jurkat T cells which are cytotoxic against U87 cells taught by GHC, and the bispecific antibody used to provide increased cytotoxicity as measured by LDH release taught by Wang et al., to create a bispecific antibody that would be known to bind and trigger various cell responses in the treatment of cancer. One of ordinary skill in the art would be motivated to combine the teachings with the expectation of creating stable bispecific Fab-scFv fragments (Elias et al. and Lu et al.) that would to induce a cytotoxic response in enhanced Jurkat T cells attached to U87 cells (GHC) and provide increased cytotoxic as measured by LDH release (Wang et al.).
Therefore, claims 1-11 are rejected as obvious over Elias et al., Chupp et al., Lu et al., GHC, and Wang et al.
Modified Rejections Necessitated by Amendment
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 1-11 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 1-11 are directed to an antibody that binds chitinase 3-like-1 (CHI3L1) and cytotoxic T-lymphocyte associated protein 4 (CTLA4). As such, the claims are 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 (CHI3L1 and CTLA4) and envisage the combination of twelve CDRs that will bind that antigen. First, even highly related CDRs may not bind the same target. See for example Kussie (in PTO-892 filed 10/21/2025) 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 et al., 1995 (in PTO-892 filed 10/21/2025) 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.
See also Koenig 2017 (in PTO-892 filed 10/21/2025) which provides a large mutation analysis study where every amino acid in both variable regions are substituted with every other amino acid. Looking at figure 1 of Koenig, the bottom half of each section (labeled VEGF) relates to the ability of the mutant to bind the original target, with blue meaning a reduced affinity and black meaning a complete loss of binding ability. In VH-CDR2, for example, mutating any given residue to cysteine, which is encompassed by the instant claims, resulted in reduced binding at 12 residues and a complete loss of binding at 5 residues. That is, at 100% of the positions, mutation to cysteine reduced or ablated the antibody’s ability to bind the target. Looking at a specific position, in 100% of the mutations of residue 55, binding was reduced (15/19) or eliminated (4/19). While residues 56-65 appear more tolerant of change, residues 50-55 are generally intolerant of change.
It is appreciated that Koenig is studying one specific antibody and there is no evidence that the instant antibodies would react in the same way. However, this is part of the problem. It is entirely unclear from the specification which residues of Applicant’s CDRs are tolerant or intolerant to change, and whether those tolerant positions are only tolerant to conservative mutations. The fact that some residues might tolerate mutation does not convey to the skilled artisan that Applicant knew which of the claimed residues were tolerant of such, i.e., does not convey that Applicant was in possession of those sequences which are mutated yet preserve the claimed function. In other words, the specification fails to convey possession of an invention commensurate in scope with what is now claimed and therefore fails to meet the written description requirement. Looking at Koenig figure 2A, ~200 mutations in the CDR region of the VH chain completely abrogates any binding. While 2B appears to indicate that the CDRs of VL are more tolerant of change than the heavy chain CDRs, still over half of the mutations reduce binding compared to the parent.
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 antibodies in Table 1 which comprises, as the heavy chain CDRs, SEQ ID NOs: 1-12 and light chain CDRs, SEQ ID NOs: 13-20 for the anti-human CHI3L1 specificity and SEQ ID NOs: 23 as the scFv for the CTLA4 specificity. The specification lists the CDR sequences within a larger variable region without denoting where the shorter CDR 1-3 regions are, nor do they denote what numbering scheme is being used so that one of ordinary skill in the art could ascertain the binding regions. Additionally, the claims do not recite the combination of exact “CDR” sequences that comprise the antibody and instead list 20 sequences that can be put together in any combination. As such, the claims are recited in a combinatorial fashion that gives rise to numerous, undefined permutations of antibody sequences that could potentially be the antibody that Applicant does not have disclosure for. The instant claims also require a particular functionality of detecting and neutralizing an epitope but without a clear structure, Applicant does not have adequate support for all antibodies capable of achieving that function.
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. 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.
However, as above, arbitrarily altering any amino acid in the CDR of an antibody is unpredictable and the specification does not convey possession of any CDRs other than those of the disclosed antibodies. Further, it is well-known in the art that specificity of a bispecific antibody stems from the interaction of twelve CDRs. Moreover, CDRs are not generally recognized as interchangeable, such that using one CDR from one antibody would not be reasonably expected to confer the same binding properties or even the same binding target when combined with two to five CDRs from other antibodies. For example, WO 2008068048 (in PTO-892 filed 10/21/2025) discloses an antibody with a heavy chain comprising three CDRs (SEQ ID NO: 2) that binds secreted aspartyl protease from Candida sp. US 20170355756 (in PTO-892 filed 10/21/2025) describes the same three CDRs in the heavy chain (C10-VH3) combined with a different light chain that binds human TDP-43. There is no evidence in the instant specification that a single CDR placed in the context of two to five other CDRS, regardless of what those other CDRs are, would result in the required function, nor that a single chain is correlated to the required function when combined with any other chain. As such, the specification fails to set forth a structure-function correlation sufficient to claim all possible antibodies defined by function and one-three CDRs or alterations thereof.
As such, the disclosure of a few antibody sequences does not convey possession of other antibodies with the same binding properties; possession of the precisely defined sequence of twelve CDRs is required.
With respect to product claims 1-11, it is recognized that information which is well known in the art need not be described in detail in the specification (MPEP §2163(II)(A)(2)). See, e.g., Hybritech, Inc. v. Monoclonal Antibodies, Inc., 802 F.2d 1367, 1379-80, 231 USPQ 81, 90 (Fed. Cir. 1986). However, sufficient information must be provided to show that the inventor had possession of the invention as claimed. MPEP §2163(II)(A)(3)(a) also discusses Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004), where a method of using a PGHS-2 inhibitor did not meet the written description as the inhibitor itself was not sufficiently described, clearly indicating that written description of the compound is still required in a method of using that compound. In this case, it is clear from the specification that the invention is in a new antibody, or at the least disclosure of a new antibody that could not have been envisaged from the prior art indicates that the prior art was not in possession of all “anti-human CHI3L1 and CTLA4 antibodies”. Thus, the prior art cannot provide sufficient written description of this genus of compounds and the specification as filed, disclosing one antibody, does not sufficiently describe the genus either as there is an unknown amount of structurally distinct antibodies in this genus (see Amgen and Centocor decisions discussed above).
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Vas-Cath, Inc., v. Mahurkar, 935 F.2d at 1563, 19 U.S.P.Q.2d at 1116. 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. An antibody described only by functional characteristic, such as antibody that detects and neutralizes CHI3L1 and CTLA4 or one of the claimed epitopes, without any known or disclosed correlation between that function and the structure of the sequence, is not a sufficient identifying characteristic for written description purposes, even when accompanied by a method of obtaining the biomolecule of interest. In re Bell, 991 F.2d 781, 26 U.S.P.Q.2d 1529 (Fed. Cir. 1993). In re Deuel, 51 F.3d 1552, 34 U.S.P.Q.2d 1210 (Fed. Cir. 1995). In the instant case, the specification provides insufficient direction or guidance concerning the relationship between the structure of the possible antibody to demonstrate possession of the breadth of the genus of anti-human CHI3L1 and CTLA4 antibodies encompassed by the instant claims, especially in view of the unpredictability of such an endeavor. The prior art as evidenced by Edwards et al., 2003 (in PTO-892 filed 10/21/2025) teaches there is a substantially huge antibody diversity produced to one single antigen target. Edwards provides evidence that over 1000 antibodies, all different amino acid sequences, were generated towards one single protein antigen target (see abstract). Without a correlation between structure and function, the claims do little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (“definition by function … does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is”).
Without this guidance or direction the skilled artisan would not consider applicant to be in possession of the claimed genus of antibodies because the skilled artisan recognizes that even seemingly minor changes made without guidance or direction as to the relationship between the particular amino acid sequence of the instantly claimed antibody and its ability to bind antigen, can dramatically affect antigen-antibody binding.
Applicant has not described the claimed invention sufficiently to show they had possession of the claimed genus of an antibody that binds CHI3L1 and CTLA4. 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).
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. 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.
What constitutes a "representative number" is an inverse function of the skill and knowledge in the art. Satisfactory disclosure of a "representative number" depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features of the elements possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus.
To provide adequate written description and evidence of possession of the claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. In the instant case, the only factors present in the claims are a recitation of one generic, broad genus that encompassed a diverse and huge number of possible antibodies that bind the disclosed epitope. The specification does not provide a consistent structure for all of the possible antibodies and fails to provide a representative number of species for the claimed genus. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, 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 they invented what is claimed.” (See Vas-Cath at page 1116).
With the exception of specifically disclosed antibodies with specific CDRs, the skilled artisan cannot envision the detailed chemical structure of all of the encompassed antibodies, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The product itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF's were found to be unpatentable due to lack of written description for that broad class. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
Therefore, claims 1-11 do not meet the written description requirement.
Response to Arguments
Applicant's arguments filed 01/20/2026 have been fully considered but they are not persuasive.
Applicant argues that the independent clam 1 has been amended to obviate the rejections. This is not found persuasive.
As noted above in the modified rejection, the pending claims still retain written description issues regarding the identity of the claimed bispecific antibody. While amendments to the claims have now been amended to include sequences regarding the structures, they are not sufficient to obviating the rejection as the claims do not sufficiently describe the structure of the antibody commensurate in scope with the instant specification. The instant claims still contain ambiguity regarding the identity of the CDRs in the bispecific antibody and thus, encompass more structures than Applicant has shown possession of in the instant disclosures.
As such, the rejection has been modified in light of amendments to the claims and still remain on the record.
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.
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/SELAM BERHANE/Examiner, Art Unit 1675
/AURORA M FONTAINHAS/Primary Examiner, Art Unit 1675