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 3/12/24. Claims 1-22 and 25-29 are pending and under examination.
Claim Objections
Claims 1 and 7 are objected to because of the following informalities:
Applicant’s list of alternatives in claim 1 uses “a” for both of the first two options, followed by “d”. The second “a” should be “b”. Further, “c” should not be skipped.
Applicant’s list of alternatives for the first region in claim 7 also skips “c”; “c” should not be skipped.
Appropriate correction is required.
Claims 9, 10, and 29 are objected to because of the following informalities:
The term “optionally” is not per se indefinite but requires analysis to determine if the term introduces ambiguity. In the above claims, the term “optionally” does not introduce any ambiguity; clearly, the “options” are not requirements nor claim limitations. For example, claim 10 is clear that the peptide linker must exist (the peptide linker directly covalently links or indirectly covalently links the first and second region), but that this linker may or may not have the sequence of SEQ ID NOs: 100.
However, this indicates that this option is exemplary. The option does not place any limitation on the claim, which is the sole purpose of words in a claim.
Where a claim(s) uses exemplary language (e.g. such as, optionally, preferably, in particular, etc.), such language does not further limit the claim but potentially causes confusion over the claim scope. See MPEP § 2173.05(d) which states that “[d]escription of examples or preferences is properly set forth in the specification rather than the claims. If stated in the claims, examples and preferences may lead to confusion over the intended scope of a claim". Therefore, exemplary language should either be positively recited as a claim limitation or removed from the claim altogether.
Appropriate correction is required.
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.
Claim 7 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 7 recites the following:
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The claim does not use “or/and” to indicate either “and” or “or”, but rather “or and” which is grammatically incorrect. It is unclear if the claim should read “and”, “or”, or “or/and”. Using the term “and”, the limitations of both the first and second region are required while “or” would indicate only one of the regions is further limited. This changes the scope of the claim and, without a clear indication of which term is correct, the scope is indefinite.
The same applies to the list for the first region. When setting forth a-j for the second region, the list terminates with “or”, clearly indicating that the second region is meant to be selected from a list of alternatives rather than possessing all of the limitations of a-j (which would have used “and”). The options a-e for the first region contain no such terminal conjunction and so it is unclear if the claim should read “or e)” or “and e)”.
Claim 7 uses both “comprising” and “consists of” to refer to the same element. A broad limitation (such as comprising) together with a narrow limitation that falls within the broad limitation in the same claim (such as “consisting of”) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In this case, this “broad embodiment – narrower subembodiment” in the same claim creates confusion over the claim scope. Either the “consisting of” is meant to affect/modify the earlier recitation, in which case the sequences “consist of” and the “comprising” is not serving as a claim limitation, or, alternately, the claim covers “comprising” and the “consisting of” serves no purpose and does not limit the claim. In both interpretations, one of the terms is not serving as a claim limitation but it is unclear which one.
Therefore, claim 7 is indefinite.
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, 7-20, 22, and 25-29 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 defines the first binding region by six CDRs. This portion of the antibody meets the written description requirement. However, the second binding region is directed to any region capable of binding human Vɣ9V2δ T cell receptor. As such, this region is 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.”
It is recognized that the “whole” of the invention is not being claimed solely by function. However, there is an inadequate description of this portion of the invention such that the claim as a whole does not meet the written description requirements.
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 (Vɣ9V2δ) and envisage the combination of six (or 3) 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. 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 eight, single-domain VHH antibodies that bind Vɣ9V2δ. However, as discussed above, without any way to determine how broad the genus of such antibodies is, 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. This does not describe the light chain of any traditional antibody that might bind this target nor does it allow the skilled artisan to envisage other VHH antibodies that still possess the required function.
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”. MPEP 2163 states “disclosure of an antigen fully characterized by its structure, formula, chemical name, physical properties, or deposit in a public depository does not, without more, provide an adequate written description of an antibody claimed by its binding affinity to that antigen, even when preparation of such an antibody is routine and conventional”. Claim 7 requires the second binding region have at least 90% identity to a sequence that contains the required CDRs. This percent identity does not require the alterations to avoid the CDRs. For example, SEQ ID NO: 130 is 247 amino acids long and so 23 amino acids can be altered and still possess 90% identity. SEQ ID NO: 30—the third CDR of this sequence—is only 17 amino acids and so could be wholly replaced within the scope of the claim. Given the evidence that even one mutation is unpredictable, the skilled artisan could not envisage how to alter these CDRs with any reasonable expectation of preserving the required binding function. 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.
The disclosure of certain specific CDR combinations does not convey possession of other antibodies with the same binding properties nor allow the skilled artisan to envisage mutated sequences within the claimed genus; possession of the precisely defined CDRs is required.
Therefore, claims 1, 7-20, 22, and 25-29 do not meet the written description requirement.
Claim 28 is 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 using the claimed antibody to treat cancer, does not reasonably provide enablement for treating all disease. 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 the medical treatment of human disease. The breadth of the claims is that the claimed antibody of claim 1—which binds CD33 and Vɣ9V2δ—can treat any and all human diseases. While Applicant’s definition of treatment is broad (specification p.10 L25), the guidance in the specification is that the antibody is therapeutic because the antibody binds two proteins relevant to cancer (p.1 L11-25). While skill in the art is high, predictability is low. The working examples and guidance in the specification are solely directed to the treatment of cancers. There is no art of record to suggest any involvement of CD33 in, e.g., Alzheimer’s disease, multiple sclerosis, lupus, COVID-19 infection, bacterial meningitis, hepatitis, etc. While claim 28 claims the antibody will treat all known diseases, the specification offers no reasoning or evidence that this is the case. The art, in contrast, does not recognize the claimed targets as being therapeutic in all cases and there is no evidence that targeting T-cells to CD33 expressing cells would benefit all diseases. It would be undue experimentation for others to test this antibody across all known diseases to determine for themselves if there is any therapeutic effect without any reasonable expectation of success.
Therefore, claim 28 is not enabled for the full scope.
Allowable Subject Matter
Claims 2-6 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.
There is no prior art rejection. As set forth in the written description rejection, CDRs are unpredictable and cannot be envisaged from the structure of the antigen nor even from the structure of other antibodies. A search of the prior art did not discover any other document that possesses the same combination of six CDRs in claim 1 and so the claimed combinations are considered non-obvious.
The term “inert” is defined in the specification at p.4 L11-15 to be an Fc region which a “minimal or no ability to bind any Fcgamma receptors, induce Fc-mediated cross-linking of FcRs, or induce FcR-mediated cross-linking of target antigens via two F c regions of individual antibodies”. The term “minimal” is a relative term. However, the art of record does not indicate that the skilled artisan would be unable to determine the metes and bounds of this term. As such, the claim is considered definite.
Copending applications 18/307146, 18/307127, 18/307076, 17/906040 claims the CD33 antibody but does not contain any claims to the Vɣ9V2δ specificity and so has not been rejected for double patenting.
Conclusion
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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/Adam Weidner/ Primary Examiner, Art Unit 1675
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