Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
DETAILED ACTION
This action is in response to claim amendments filed 1/5/24. Claims 32-50 are pending and under examination.
Drawings
The drawings are objected to because:
Figure 1: disclosed sequences must be identified by SEQ ID either in the drawing or the brief description of that drawing. There are four sequences shown in figure 1 but the description only sets forth two SEQ IDs. The description assigns these two SEQ IDs to the “top portion”, which is presumed to be the two sequences in the upper third of the figure. This means that the middle and bottom sequences are not addressed by a SEQ ID either in the drawing or specification. The middle and bottom sequences must also be identified even if these are still the same sequences.
Figures 2-21: see objection to figure 1.
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
Residues 26-33 of both SEQ ID NOs: 34 and 36 are identical (GFTFTSSD).
Residues 97-110 of both SEQ ID NOs: 34 and 36 are identical (ARERPRRRGGGFDI).
Residues 51-58 of SEQ ID NO: 34 is MNPNSGNT.
Residues 51-58 of SEQ ID NO: 36 is MNPKSGNT.
Residues 27-32 of SEQ ID NO: 38 is QGISNYL.
Residues 50-52 of SEQ ID NO: 38 is AAS.
Residues 89-97 of SEQ ID NO: 38 is QKYNSAPWT.
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 39-40 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 39 is directed to an antibody defined by a partial sequence (the heavy chain) while claim 40 is directed to an antibody defined by a partial sequence (the light chain).
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 (GD2) 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 (cited on form 892) 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 (cited on form 892) 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.
Claims 39 and 40 do not claim any specific functionality of the antibody. However, the specification discloses that the instant antibodies are anti-GD2 antibodies (paragraph 42). As such, the description of only half of an antibody does not adequately describe any antibody that binds a target other than GD2. Note that an arbitrary sequence does not possess any utility and the skilled artisan reading the instant specification would understand that, while the function is not claimed, claims 39 and 40 are a description of an anti-GD2 antibody. No antibody that binds any other antigen is described by the specification. Further, description of half the antibody also does not adequately describe an antibody that binds GD2 because it is the combination of six CDR sequences that bind the target antigen. See MPEP §2163(II)(A)(2) indicating that the specification is inspected to understand how Applicant provides support for “the claimed invention”. While the claim is solely to one of the two chains, the specification provides support solely in the context of both chains combined to create a functional antibody; half of such an antibody is not disclosed as having any utility or function itself.
As additional evidence, WO 2008068048 (cited on form 892) discloses an antibody with a heavy chain comprising three CDRs (SEQ ID NO: 2) that binds secreted aspartyl protease from Candida sp. US 20170355756 (form 892) 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 one chain placed in the context of any other chain, regardless of what that chain is, would result in any function. Further, this makes clear that a description of a single chain is not a description of “the invention”, which the specification discloses only as an anti-GD2 antibody. As such, the specification fails to set forth a structure-function correlation sufficient to claim all possible antibodies defined by three CDRs.
Therefore, claims 39-40 do not meet the written description requirement.
Claims 32-40 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 the claimed half antibody (heavy chain or light chain) combined with the respective partner disclosed in the specification, does not reasonably provide enablement for a single chain without a corresponding partner or with a partner other than the ones disclosed. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
There are many factors considered when determining if the disclosure satisfies the enablement requirement and whether any necessary experimentation is undue. These factors include, but are not limited to: 1) nature of the invention, 2) breadth of claims, 3) amount of direction or guidance by the inventor, 4) relative skill of those in the art, 5) level of predictability in the art, 6) state of the prior art, 7) existence of working examples, and 8) quantity of the experimentation needed to make or use the invention. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)
The nature of the invention is polynucleotides encoding either the light chain or the heavy chain of an antibody or those chains themselves. The breadth of the claims is that this half of an antibody (or polynucleotide encoding half an antibody) is sufficient to make an antibody that binds GD2 either alone or when combined with any arbitrary alternate chain. It is noted that no function or property of the instant polynucleotides or antibodies is claimed. Per MPEP §2164, where a composition is not limited by a recited use, any enabled use that would reasonably correlate to the entire scope of the claim is sufficient. The broadest disclosed use of the claimed polynucleotides and single chains is in the making of an antibody that binds GD2 (see, e.g., paragraph 42). Therefore, it is this utility for which the compositions are being evaluated.
The amount of guidance in the specification is that the light chain may be combined with one of two heavy chains to make such an antibody, while the two heavy chains must be combined with a single, specific light chain to make such an antibody. However, the art recognizes that there is a great deal of unpredictability when set to make such an antibody.
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 (GD2) 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 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 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.
As additional evidence, WO 2008068048 (cited on form 892) discloses an antibody with a heavy chain comprising three CDRs (SEQ ID NO: 2) that binds secreted aspartyl protease from Candida sp. US 20170355756 (form 892) 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 one chain placed in the context of any other chain, regardless of what that chain is, would result in any function while the art recognizes that a single chain may possess an entirely different function when placed in the context of another chain.
See also Gudas (US20040018198; form 892), where the instantly claimed light chain CDRs are part of an antibody that binds a wholly different target than GD2. Figure 19 of Gudas shows the CDR sequences of 45C9 (SEQ ID NO: 86), which comprises identical sequences in the CDRs as the instant light chain of SEQ ID NO: 38 but binds CA IX. Gudas also teaches polynucleotides encoding these antibodies (claim 15). Owens (US 20050013809; form 892) teaches SEQ ID NO: 38, which also contains the same light chain CDR sequences but binds a “drug of abuse” (claim 2). This further establishes that combining this light chain is unpredictable and would require undue experimentation on the part of others to make and test every combination of the claimed heavy chain with all possible light chains to determine if the antibody has any function at all and specifically the function of binding GD2. The same is true mutatis mutandis for the claimed heavy chain.
Therefore, claims 32-40 are not enabled for their full scope.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 36 is/are rejected under 35 U.S.C. 102(a)(1-2) as being anticipated by Gudas (US20040018198).
Figure 19 shows the CDR sequences 45C9 (SEQ ID NO: 86), which comprises identical sequences in the CDRs as the instant light chain of SEQ ID NO: 38. Gudas also teaches polynucleotides encoding these antibodies (claim 15). This anticipates every limitation of instant claim 36.
Allowable Subject Matter
Claims defined by six CDRs are not rejected herein. Six CDRs define the binding properties of an antibody and such antibodies meet the requirements of §112(a). Further, no art of record discloses the same combination of six CDR sequences. As antibodies are unpredictable (see above), the instant combination is considered non-obvious.
Conclusion
Claim 43 claims the antibody is a human antibody. The specification provides a special definition of this term at paragraph 43: “an antibody or functional fragment thereof that has a human variable region and/or a human constant region or a portion thereof corresponding to human germline immunoglobulin sequences”. The specification discloses that the antibodies of the instant invention were obtained from humans after artificial vaccination (paragraph 41). Thus, the instant specification only describes CDRs of a human antibody. However, claim 32 only requires these human CDRs and the rest of the variable region may be from another species, while the special definition requires that the whole of the variable region and/or the whole of the constant region is also human. Thus, the claim complies with the written description requirement as well as §112(d).
The specification discloses that the antibodies of the instant invention were obtained from humans after artificial vaccination (paragraph 41). Thus, while the antibodies themselves are the natural response in humans to such immunization, there is no evidence of record to suggest that these antibodies would have been produced by natural means. Since the antibodies are only elicited after the non-natural vaccination, the antibodies are not deemed to be natural products and so the claims comply with §101.
WO2018160993 (form 892) is made of record. This document discloses the instantly claimed sequences. However, the document does not qualify as prior art (no prior art rejection over this document) and has no corresponding US application nor does it share any inventors/assignees (no double patenting rejection).
US 9856324, US 10906988, and US11760809 were considered for double patenting. However, these patents are all limited to a combination of sequences which are mutually exclusive from the instantly claimed sequences. As set forth above, an antigen or even another antibody that binds the same antigen does not inform the skilled artisan of any other sequence which predictably binds that same antigen. As such, the instant claims are considered patentably distinct.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ADAM M WEIDNER whose telephone number is (571)272-3045. The examiner can normally be reached M-T 9-18; W-R 9-15.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at 571-272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Adam Weidner/ Primary Examiner, Art Unit 1675
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