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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 02/23/2026 has been entered.
Response to Amendment
Applicant’s remarks and amendments to the claims received 02/23/2026 have been acknowledged. Claims 1, 13, and 15 have been amended. Claim 25 is newly added. The amendments to the claims overcome claim objections and the rejection made under 35 USC 112(b) previously set forth in the Final Rejection of 11/25/2025.
Specification
The disclosure is objected to because of the following informalities: In accordance with 37 C.F.R. 1.74, when there are drawings, there shall be a brief description of the several views of the drawings and the detailed description of the invention shall refer to the different views by specifying the numbers of the figures, and to the different parts by use of reference letters or numerals (preferably the latter). For example, if the drawings show Figures 1A, 1B, and 1C and the brief description of the drawings refers only to Figure 1, the brief description will be objected and applicant required to provide a brief description of Figures 1A, 1B, and 1C. (see MPEP 608.1(f)). In this case, the Drawings of 02/18/2022 show the following figures that are not described in the Brief Description of the Drawings: Fig. 4A, Fig. 4B, Fig. 4C, Fig. 12A, Fig. 12B, Fig. 12C, Fig. 12D, Fig. 14A, Fig. 14B, Fig. 14C, Fig. 14D, Fig. 27A, Fig. 27B, Fig 27C, Fig. 27D, Fig. 29A, Fig. 29B, Fig. 29C, and Fig. 29D. Additionally, Figure 2 has four labeled panels (A)-(D) which are not referenced in the Brief Description of the Drawings.
Appropriate correction is required.
Drawings
The drawings of 02/18/2022 are objected to because the image for Figure 25 described in the Brief Description of the Drawings is cut off/missing. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Interpretation
For purposes of examination, the limitation that the antibody is “obtainable from the hybridoma having the ECACC accession number 19080602” as recited in claim 1 is interpreted as identifying the parental antibody from which variants are generated. This interpretation is applied because claim 1 recites antibodies having up to one amino acid difference in each CDR relative to the recited sequences, which indicates the claimed antibodies encompass variants derived from the recited hybridoma rather than being limited to the specific antibody produced by the hybridoma itself. Claim 15 is interpreted in a similar fashion.
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.
Written Description
Claims 1-6, 13, 15-17, and 25 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.
Claim 1 recites heavy and light chain CDRs of anti-C7 antibody clones wherein each CDR represents a partially defined structure that can vary by 1 amino acid relative to the recited sequences.
Claim 13 further recites VH and VL domains that represent partially defined structures in which at most 20% of the amino acid sequences can vary in the CDRs and/or framework regions.
The guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, § 1 "Written Description" Requirement make clear that if a claimed genus does not show actual reduction to practice for a representative number of species, then the Requirement may be alternatively met by 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 genus (MPEP 2163).
In The Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412) 19 F. 3d 1559, the court held that disclosure of a single member of a genus (rat insulin) did not provide adequate written support for the claimed genus (all mammalian insulins). In this same case, the court also noted:
“A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is. See Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen). It is only a definition of a useful result rather than a definition of what achieves that result. Many such genes may achieve that result. 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, 1521, 222 USPQ 369, 372-73 (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.”
The court has further stated that “Adequate written description requires a precise definition, such as by structure, formula, chemical name or physical properties, not a mere wish or plan for obtaining the claimed chemical invention.” Id. at 1566, 43 USPQ2d at 1404 (quoting at 1171, 25 USPQ2d at 1606). Also see (CAFC 2002). Enzo-Biochem v. Gen-Probe Fiers, 984 F.2d 01-1230.
Claim 1 recites heavy and light chain CDRs of anti-C7 antibody clones wherein each CDR represents a partially defined structure that can vary by 1 amino acid relative to the recited sequences. Such variation can occur, for example, by amino acid substitution, deletion, or insertion. However, there is no guidance provided in the specification about which specific amino acids mutations can made in the heavy and light chain CDRs of the antibodies or antibody fragments such that the ability of the antibody to bind to C7 and inhibit complement activation is retained. Indeed, it is well-known in the art that amino acid substitutions in the antibody in the CDR domains can negatively impact binding activity (see, e.g. Piche-Nicholas et al, see in particular, Abstract, of record; Colman, see entire document particularly Page 33, Col. 2; and Rudikoff et al, see Abstract) –and conservative amino acid substitutions are no exception. For example, site-directed mutagenesis studies of the NC10 scFv antibody fragment revealed that the tyrosine at position 32 (TyrL32) is a critical residue for binding to influenza virus neuraminidase since mutation of the TyrL32 residue to phenylalanine (a conservative amino acid substitution) resulted in a significant reduction in binding affinity (Dougan et al, see Abstract). Thus, even a single conservative amino acid substitution at a critical residue can significantly reduce or abolish binding to target antigen. Accordingly, in the context of antibody-antigen interactions, the effect of amino acid mutations –even conservative substitutions— on binding affinity is not readily predictable. The level of skill and knowledge in the art is such that one of ordinary skill would not be able to readily identify without further testing which amino acid mutations can be made in each CDR sequence such that the ability of the antibodies to bind to C7 and inhibit complement activation is retained. Moreover, while the CDR sequences of clones 17E7 (ECACC Accession No. 19041601) and 7D31 (ECACC Accession No. 19080601) are disclosed, the specification does not appear to disclose the CDR sequences of clone 59E7 (ECACC Accession No. 19080602) presently recited in the claims. Because the claims appear to define antibodies in terms of amino acid differences relative to parental CDR sequences, the scope of antibody variants “obtainable from the hybridoma having the ECACC Accession number 19080602” (clone 59E7) as recited in claims 1 and 15 cannot be readily identified in the absence of the parental sequence of clone 59E7 (see also 35 USC 112(b) rejection below). All claims dependent on claim 1 fail to cure the deficiencies of claim 1 and are thus also rejected.
Similarly, claim 13 recites an antibody or antibody fragment comprising the amino acid sequence of VH chain having at least 80% homology to SEQ ID NO: 1, 11, or 19 and/or the amino acid sequence of a VL chain having at least 80% homology to SEQ ID NO: 5, 15, or 23. As presently written, the VH and VL chains represent partially defined structures in which at most 20% of the amino acid sequences can vary. Such variation can be caused by different types of amino acid mutations and can encompass those mutations made in the CDRs of the antibodies. However, there is no guidance provided in the specification about the location and type of amino acid mutations that can be made in the VH and/or VL chains of the antibodies –particularly in the CDR sequences – such that the ability of the antibody to bind to C7 and inhibit complement activation is retained.
Therefore, the claimed genus of antibodies lacks adequate written description because there does not appear to be any correlation between the structure of the claimed antibodies or fragments thereof and the function of binding to C7 and inhibiting complement activation. Thus, one of ordinary skill in the art would reasonably conclude that the applicant was not in possession of the full breadth of the claimed genus of antibodies or fragments thereof that bind to C7 and inhibit complement activation at the time the instant application was filed.
Scope of Enablement
Claims 1-6, 13, 15-17, and 25 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for an anti-C7 antibody clones having the CDR sequences expressly disclosed in the specification, does not reasonably provide enablement for anti-C7 antibody variants comprising an undefined amino acid mutation within each of the CDR sequences, wherein the specification provides no data or technical guidance demonstrating that such antibody variants retain binding to C7 and inhibit complement activation. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
The nature of the invention relates to anti-C7 antibodies and fragments thereof and their use in inhibiting complement activation in order to treat or prevent a disease associated with the dysregulation of complement in a subject (see Technical Field, Page 1 of Specification).
Claim 1 is broadly drawn to an antibody or fragment thereof that binds complement protein C7 in isolation or as part of a protein complex and inhibits complement activation, wherein the anti-C7 antibody comprises heavy and light chain CDRs each having 1 amino acid difference to the recited sequences.
The specification teaches that several anti-C7 monoclonal antibody clones were generated including 17E7, 59E7, 3B11, 2H2, and 73D1 and tested for the ability to bind to C7 as well as inhibit complement activation. All antibodies bind to human and cynomolgus C7 as determined by ELISA (Page 57, Ln. 30-35 and Table 1). Further, it was found that the anti-C7 antibodies efficiently inhibited complement activation (Table 1). Clones 17E7 and 73D1, in particular, inhibited in vivo complement activation as measured by a classical pathway hemolysis assay (Page 55, Ln. 3-21; Page 61, Ln. 15-16 to Page 62, Ln. 1-21). However, the specification does not provide evidence that any number or type of amino acid mutations in the CDRs of the claimed antibodies predictably results in the recited functional outcomes (i.e. binding to C7 either alone or in complex and inhibiting complement activation). Further, the specification lacks sufficient guidance on which amino acid residues, particularly in the CDR sequences, are amenable to mutagenesis without disruption of antigen binding and inhibitory activity. Additionally, while the CDR sequences of clones 17E7 (ECACC Accession No. 19041601) and 7D31 (ECACC Accession No. 19080601) are disclosed, the specification does not appear to disclose the CDR sequences of clone 59E7 (ECACC Accession No. 19080602) presently recited in the claims. Given that clones 17E7 and 7D31 differ from each other by more than a single amino acid in each CDR [see, e.g., 17E7 HCDR3: SGGYDVGGLDY (SEQID NO: 4) vs 7D31 HCDR3: GNYDPY (SEQ ID NO: 22)] (see Sequence Listing), it is not likely that clone 59E7 is so similar in sequence that it can serve as a template for generating variants of both clones 17E7 and 7D31 within the limitation of “up to 1 amino acid difference” as presently recited in claims 1 and 15 (i.e. wherein the antibody is obtainable from a hybridoma having the ECACC Accession number 19080602) (see also 35 USC 112(b) rejection below). All claims dependent on claim 1 fail to cure the deficiencies of claim 1 and are thus also rejected.
It is well-known in the art that amino acid mutations in the CDR domains of an antibody can negatively impact binding activity (see, e.g. Piche-Nicholas et al, see in particular, Abstract, of record; Colman, see entire document particularly Page 33, Col. 2; and Rudikoff et al, see Abstract) –and conservative amino acid substitutions are no exception. For example, site-directed mutagenesis studies of the NC10 scFv antibody fragment revealed that the tyrosine at position 32 (TyrL32) is a critical residue for binding to influenza virus neuraminidase since mutation of the TyrL32 residue to phenylalanine (a conservative amino acid substitution) resulted in a significant reduction in binding affinity (Dougan et al, see Abstract). Thus, even a single conservative amino acid substitution at a critical residue can significantly reduce or abolish binding to target antigen. Accordingly, in the context of antibody-antigen interactions, the effect of amino acid mutations –even conservative substitutions— on binding affinity is not readily predictable.
Similarly, claim 13 recites an antibody or antibody fragment comprising the amino acid sequence of VH chain having at least 80% homology to SEQ ID NO: 1, 11, or 19 and/or the amino acid sequence of a VL chain having at least 80% homology to SEQ ID NO: 5, 15, or 23. As presently written, the VH and VL chains represent partially defined structures in which at most 20% of the amino acid sequences can vary. Such variation can be caused by different types of amino acid mutations and can encompass those mutations made in the CDRs of the antibodies. However, as stated above, there is no guidance provided in the specification about which specific amino acids mutations (including location and type) can be made in the VH and/or VL chains of the antibodies or antibody fragments—particularly in the CDR sequences – such that the ability of the antibody to bind to C7 and inhibit complement activation is retained.
A person of ordinary skill in the art at the time of filing would have had experience in antibody engineering, including CDR mutagenesis and screening techniques. Even at this high level of skill, however, the effect of randomly mutating amino acids in the CDRs on antigen binding and inhibitory activity cannot be readily predicted without additional testing. In Amgen Inc. v. Sanofi, Aventisub LLC, 987 F.3d 1080 (Fed. Cir. 2021), which the Supreme Court affirmed, the Federal Circuit relied on evidence showing that the scope of the claims encompassed millions of antibodies and that it was necessary to screen each candidate antibody in order to determine whether it met the functional limitations of the claim. Id. at 1088. Consequently, the Federal Circuit concluded that there was a lack of enablement (MPEP 2164.06). Thus, the level of skill does not obviate the need for substantial experimentation across the full scope of the claimed genus especially given that there is no guidance provided in the specification or prior art on which amino acid mutations (including location and type) can be made in the CDR sequences that will result in a functional variant that still binds to the target antigen C7 and inhibits complement activation.
Therefore, the specification is not enabling over the full scope of the claims.
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 1-6, 13, 15-17, and 25 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.
Claim 1 recites an anti-C7 antibody comprising up to one amino acid difference in each CDR relative to the parental sequences of clone 17E7 (HCDRs of SEQ ID NOs: 2-4 and LCDRs of SEQ ID NOs: 6-8) or clone 73D1 (HCDRs of SEQ ID NOs: 20-22 and LCDRs of SEQ ID NOs: 24-26), while also reciting that the antibody is obtained from the hybridoma of clone 59E7 (ECACC deposit number 19080602) (see Brief Description of the Figures on Page 8; Sequences listed on Pages 62-65). Thus, it is unclear if the claim is directed to (i) the specific antibody produced by the hybridoma of clone 59E7 or (ii) variant antibodies defined by sequence differences relative to clones 17E7 or 7D31. To the extent that “obtainable from the hybridoma having the ECACC accession number 19080602” (i.e. clone 59E7) is intended to define a starting antibody that is subsequently modified, the claim still fails to clarify how an antibody derived from clone 59E7 would be defined by sequence differences relative to clones 17E7 or 7D31. While the CDR sequences of clones 17E7 (ECACC Accession No. 19041601) and 7D31 (ECACC Accession No. 19080601) are disclosed, the specification does not appear to disclose the CDR sequences of clone 59E7 (ECACC Accession No. 19080602) presently recited in the claims. Because the claims appear to define antibodies in terms of amino acid differences relative to parental CDR sequences, the scope of antibody variants “obtainable from the hybridoma” of clone 59E7 cannot be determined with reasonable certainty. However, given that clones 17E7 and 7D31 differ from each other by more than a single amino acid in each CDR [see, e.g., 17E7 HCDR3: SGGYDVGGLDY (SEQID NO: 4) vs 7D31 HCDR3: GNYDPY (SEQ ID NO: 2)] (see Sequence Listing), it is not likely that clone 59E7 is so similar in sequence that it can serve as a template for generating variants of both clones 17E7 and 7D31 within the limitation of “up to 1 amino acid difference” as presently recited in claim 1. Similarly, claim 15 recites that the antibody is obtainable from the hybridoma of clone 17E7 (ECACC Accession No. 19041601), 7D31 (ECACC Accession No. 19080601), or 59E7 (ECACC Accession No. 19080602). For reasons discussed above for claim 1, it is unclear is directed to (i) the specific antibody produced by any one of the hybridomas of clones 17E7, 7D31, or 59E7 or (ii) variant antibodies defined by sequence differences relative to the clones. As such, the claims do not set forth the metes and bounds of the patent protection desired. Claims dependent directly or indirectly from claim 1 do not cure the deficiencies of claim 1 and are also rejected.
Response to Arguments
Applicant's arguments filed 02/23/2026 have been fully considered but they are not persuasive.
With respect to rejections made under 35 USC 112(a) written description, Applicant argues that claim 1 complies with the written description requirement because the skilled artisans understand which specific, conservative mutations (additions, deletions, or replacements) can be made to the recited sequences while retaining their activity. As an example, Applicant states that the skilled person understands that conservative mutations, such as the replacement of valine with the structurally and chemically similar isoleucine (and other similar mutations) would not substantially affect the activity of the antibody or antibody fragment. Thus, Applicant asserts that the skilled person would have no difficulty in carrying out the claimed invention without undue experimentation and would thus conclude the inventors had possession of the invention at the time of filing. Applicant further argues that claim 13 as amended also complies with the written description requirement for substantially the same reasons.
In response to Applicant’s argument, the Examiner notes that a single amino acid substitution in the antibody-antigen interface –even if conservative – can significantly disrupt or abolish antigen binding. For example, site-directed mutagenesis studies of the NC10 scFv antibody fragment revealed that the tyrosine at position 32 (TyrL32) is a critical residue for binding to influenza virus neuraminidase since mutation of the TyrL32 residue to phenylalanine - a conservative amino acid substitution - resulted in a significant reduction in binding affinity (Dougan et al, see Abstract). The specification does not provide any evidence or guidance on which specific amino acid residues in the CDR sequences are amenable to conservative substitution without disrupting binding to the target antigen C7. As such, artisans would have to engage in additional trial-and-error experimentation to determine which antibody variants having a single amino acid mutation in each of the CDRs retain binding to complement C7 and inhibition of complement activation. Therefore, the rejection under 35 USC 112(a) is maintained.
The amendments to the claims overcome claim objections and the rejection made under 35 USC 112(b) previously set forth in the Final Rejection of 11/25/2025. Therefore, this rejection has been withdrawn. However, upon further consideration, a new ground of rejection is made under 35 USC 112(b) as discussed in detail above in the present Office Action.
Conclusion
No claims are allowable.
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/LIA E TAYLOR/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641