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 with traverse of Group I, claims 1-33 and 35-38, and species: S as X1, G as X2, A as X3, F as X4, S as X5, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 15, SEQ ID NO: 6, SEQ ID NO: 3, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NOs: 21 and 13, an antibody, chemotherapeutic agent and cytotoxic agent, alpha emitter, auristatins, 135-235 mg, CTLA4, WNT protein, and a method of treating cancer comprising a step of administering the antibody to a patient with cancer in the reply filed 10/23/2025 is acknowledged. The traversal is on the ground(s) that Liu et al. does not suggest or contemplate anti-CD46 antibodies that exhibit pH-dependent binding or disclose how to make such antibodies. This is not found persuasive because as recited, the instant claims do not fully define the antibody by sequence or by targeted antigen. There are substitutions to be made within the CDR sequences, which broadens the scope of the claim greatly to a number of CDRs, preferably to the same target, that are encompassed under such a wide scope that share similarity with the partial sequences of the claims. A such, the teachings of Liu et al. fit into this broad scope as comprising antibodies that can bind to CD46, and thus were used to break unity.
Claims 18-24, 34-35, 38, and 40 are withdrawn from consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions and species, there being no allowable generic or linking claims.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 10/23/2025.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-6, 17, 25-33, and 36-37 are now under consideration in the instant Office Action.
Withdrawn Objections
Objections to the drawings are hereby withdrawn in view of a new copy filed with amendments that addressed the outstanding issues and added sequence identifiers to unlabeled sequences in the specification.
Maintained Objections
Claim Objections
Claim 33 is objected to because of the following informalities: there is a typo in the instant claim when reciting what is presumed to be “group” as “grou0p” Appropriate correction is required.
Response to Arguments
Applicant's arguments filed 07/08/2026 have been fully considered but they are not persuasive.
Applicant does not address the claim objections, nor did they amend the claims to overcome them. As such, the objections to the claim remain on the record.
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, 5-6, 17, and 25-33 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, 5-6, 17, and 25-33 are directed to an antibody that binds to CD46. The instantly claimed antibody for CD46 suffers from written description issues due to the combinatorial language of the sequences as well as the breadth of amino acid substitutions to sequences encompassed within the claims. 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 (CD46) 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 (PTO-892 filed 01/13/2026) 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 (PTO-892 filed 01/13/2026) 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.
The instant specification discloses 9 heavy and light chain variable region sequences and 13 heavy and light chain CDR sequences that make up an anti-CD46 antibody on pages 88-90. 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. Some of the CDRs contain substitutions at multiple points, with the substitutions being listed as “X₁ is S or L; X₂ is G or W; X3 is S or A; X4 is H or F, X5 is S or E; with the proviso that X₁, X₂, X₃, X₄ and X₅ cannot be S, G, S, H and S, respectively, at the same time”. In addition to the substitutions that can occur in the sequences for L1 and L2, the claims set up conditions for a listed of the combinations of substitutions that are permissible, but does not provide sequences for each potential combination of substitutions that can arise from the claim language. These substituted CDRs can be placed in the context of other CDRs that are substituted in a variety of ways, without properly defining the combination of six that comprise an antibody. The specification does not convey to the skilled artisan that Applicant was in possession of the large, immeasurable number of potentially unique CDRs, let alone combinations of six CDRs that form complete antibodies, that can arise from this level of substitution.
Additionally, the instant claims refer to the six CDRs that comprise the antibody in a combinatorial fashion wherein one CDR sequence is selected and can be placed in the context of any other CDR(s). Applicant has not provided sufficient disclosure and identities of all the CDRs of the antibodies that can arise from the combinatorial and substitutional language that is encompassed by the claims. Applicant has not demonstrated that they are in possession of all the molecules that fall within the immense scope of the claim that are able to achieve the claimed function.
Instant claims 5-6 recite heavy and light chain variable region sequences with at least 80% or 90% identity to SEQ ID NOs: 11, 13, 14, 16, 18, 20, and 21. In addition to claims 5-6 depending from a claim that fails to fully recite the structure of the CDRs due to combinatorial language, there is no limitation or exclusion in the claim language that prevents the modifications from occurring within the CDR region due to the claim language allowing up to at least 80% or 90% sequence identity, which widens the scope of the claim to encompass an immense number of unknown molecules that share at least 80% identity to the claimed sequence and can bind to the claimed receptor. Applicant has not demonstrated that they are in possession of all the molecules that fall within the immense scope of the claim that are able to achieve the claimed function.
Further, it is well-known in the art that specificity of an antibody stems from the interaction of six 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 (PTO-892 filed 01/13/2026) discloses an antibody with a heavy chain comprising three CDRs (SEQ ID NO: 2) that binds secreted aspartyl protease from Candida sp. US 20170355756 (PTO-892 filed 01/13/2026) describes the same three CDRs in the heavy chain (C10-VH3) combined with a different light chain that binds human TDP-43. The instant claims fail to specify what the specific sequences, substitutions included as part of such, constitute the six CDRs of the antibody capable of binding to the target antigen.
As such, the disclosure of a large list of unknown, potential CDRs dependent upon substitutions does not convey possession of all the potential antibodies that would arise from this combination as claimed and have the same binding properties; possession of the precisely defined sequences of the three CDRs per specificity is required. As written, the instant claims recite a number of unknown CDRs that can be substituted with a combination of five other unknown CDRs, replete with their own combinations of substitutions, to construct an undefined antibody. 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.
With respect to product claims 1, 5-6, 17, and 25-33, 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-CD46” antibodies. Thus, the prior art cannot provide sufficient written description of this genus of compounds and the specification as filed, 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 binds to CD46, 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-CD46 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 (PTO-892 filed 01/13/2026) 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 antibodies that binds to CD46. 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 CDR sequences and heavy and light chain variable sequence pairs, the skilled artisan cannot envision the detailed chemical structure of all of the potential encompassed combination of 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, 5-6, 17, and 25-33 do not meet the written description requirement.
Response to Arguments
Applicant's arguments filed 07/08/2026 have been fully considered but they are not persuasive.
Applicant argues “the examiner has failed to overcome this presumption with sufficient evidence or reasoning. The Examiner’s conclusory assertions, without analysis of the skilled artisan’s knowledge or state of the art, are insufficient to support a written description rejection”. This is not found persuasive.
The written description supra discusses the issues with the combinatorial language of the CDRs. While there are sequences in the claims that fulfill some of the potential substitutions of amino acids, Applicant has not provided the necessary disclosure for all the combinations permitted by the language of the claims. Additionally, these CDRs can be mixed and matched within these possibilities which leads to a large number of antibody embodiments that are not described in the disclosure. Language regarding substitutions are permitted in the instant claims; however, they must be in line with the disclosure and can only claim what Applicant has adequate possession of.
Applicant argues that “the claims recite and define all possible CDR sequences” and that only 31 combinations of CDRs are possible from the claim language. This is not found persuasive.
In reference to the amino acid substitutions in the claims, Applicant argues that only 31 sequences can arise from the recitations in the claims. This is unclear because there are only 22 sequences disclosed in the entire listing, which would not cover the sequences for the number of possible CDRs encompassed by the claims, let alone include other sequences such as those for the variable regions and heavy and light chains. Additionally, the claims describe these CDRs as being able to be paired with any other CDR(s), which are also subject to amino acid substitution. This gives rise to combinations of sequences that comprise antibodies that are not fully described in the specification or have been considered by Applicant. The claims as written have listed out amino acid substitution options, but the specification only defines some of the possible permutations. For example, if for L1 (SEQ ID NO: 1) S was substituted at X1, W was substituted at X2, and A was substituted at X3, one would not be able to find a corresponding sequence in the specification or the sequence listing despite these options being recited in the instant claims. There exists no sequence for this potential permutation in the specification amongst numerous others. As such, Applicant has not considered and shown possession of the scope of CDRs that are being claimed in this combinatorial fashion.
Applicant argues that “the examiner appears to suggest that functional limitations (pH-dependent binding) create written description issues.” This is not found persuasive.
Given that the anti-CD46 antibody structure has not been defined by the instant claims, any recitation of what the antibody can do remains a functional limitation bound to its undefined structure. The scope of the claims extends far beyond what is disclosed in the instant specification.
Therefore, the written description rejection has been modified in view of amendments to the claims.
Conclusion
Claims 2-4 and 36-37 are 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.
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 SELAM BERHANE whose telephone number is (571)272-6138. The examiner can normally be reached Monday - Friday, 9-5.
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/SELAM BERHANE/Examiner, Art Unit 1675
/AURORA M FONTAINHAS/Primary Examiner, Art Unit 1675
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