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 7/7/26. Claims 1-2, 4, 10, 17, 20-22, 24, 41, 44, 51, 53-54, 57, 87, 92-93, and 97 are pending and under examination.
Withdrawn
The objection to the specification is withdrawn in light of the amendments.
The claim objections are withdrawn in light of the amendments.
The §112b rejection is withdrawn in light of Applicant’s arguments. Applicant states on the record that “the optional limitations identify embodiments that may, but need not be, present”, i.e., are not claim limitations as they do not serve to limit the claim (need not be present).
The §112a rejection is withdrawn in light of the amendments.
Current Objections
Drawings
The objection to the drawings (see action 4/9/26) is maintained. However, it is noted for the record that Applicant’s color drawings correct all of the deficiencies set forth. While this objection is being maintained because the petition to accept color drawings has not yet been decided, the Examiner acknowledges that should this petition be granted, the drawing objection will be withdrawn.
Claim Objections
Claims 17 and 51 are objected to because of the following informalities:
Applicant states (remarks 7/7/26) that the use of “optionally” is meant to indicate embodiments that need not be present. The use of “optionally” is not used to describe additional optional elements but rather shares a genus-species relationship. For example, claim 17 recites the genus of “therapeutic agent” where this genus is “optionally” a particular type of therapeutic agent. This supports the conclusion that these “options” are merely examples of the therapeutic agent and do not serve to limit the claim in any way.
The claim(s) currently use exemplary language (e.g. such as, optionally, preferably, in particular, etc.). 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.
Maintained Rejections and New 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 57, 87, 92, 93, and 97 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.
Independent claims 57, 87, and 92 are directed to ALK antibodies claimed by function and a partial structure. As such, the claim is directed to an antibody defined entirely by function (binding).
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 (ALK) 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 (previously cited) 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 (previously cited) 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.
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 claims allow for altering 10% of the claimed sequences. As an example, SEQ ID NO: 14 is 202 amino acids and so 20 amino acids may be altered, whereas all three CDRs amount to 18 amino acids (SEQ ID NOs: 18-20). The specification as filed does not provide sufficient guidance to predict which amino acids must be preserved and which may be altered. Thus, the claims encompass arbitrarily altering the entirety of the known binding region of the antibody. L-CDR2 comprises YTS in all three embodiments yet the claims allow for altering these three amino acids with no reasonable expectation that function will be preserved. Moreover, some embodiments appear to require more amino acids (such as LCD2 being YTSSLHS) and the specification does not provide sufficient guidance to predict whether or not these could be truncated to the YTS of other embodiments or if, in certain cases, the surrounding amino acids are required and, if so, when.
The specification discloses three antibodies, which are 100% identical to the three combinations claimed. However, as discussed above, there is no way to determine from these three antibodies the extent of mutation tolerance of said antibodies which are only 90% identical. The disclosure of these specific antibodies would not allow the skilled artisan to envisage the specific structure of such antibodies with the claimed functions.
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”. It is similarly well-known in the art that specificity of an antibody stems from the interaction of six CDRs and CDRs are not generally recognized as interchangeable, such that using three CDRs from one antibody would not be reasonably expected to confer the same binding properties or even the same binding target when combined with three CDRs of some arbitrary sequence. For example, WO 2008068048 (previously cited) discloses an antibody with a heavy chain comprising three CDRs (SEQ ID NO: 2) that binds secreted aspartyl protease from Candida sp. US 20170355756 (previously cited) 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 chain (either heavy or light) 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 three CDRs or alterations thereof.
This is also highlighted when comparing the antibodies of US 20150196663 (previously cited) to those of US 20150266947 (previously cited). Both publications screened for antibodies using the same library of antibodies (Sheet’s library; ‘663 paragraphs 50, 69 and ‘947 paragraph 131). The six CDRs of ‘947 SEQ ID NO: 11 and reference scFv15 are aligned below:
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The two antibodies share identical CDRs (e.g., CDR-L1), similar CDRs (e.g., CDR-H1, CDR-L2), and highly disparate CDR sequences (e.g., CDR-H3, CDR-L3). One could not envisage which portions of the CDRs are necessary to impart the claimed binding properties or which could be mutated without affecting such properties, nor does the instant specification provide guidance to this effect. As such, the disclosure of one antibody sequence does not convey possession of other antibodies with the same binding properties; possession of the precisely defined sequence of six CDRs is required.
Therefore, claims 57, 87, 92, 93, and 97 do not meet the written description requirement.
Response to Arguments
Applicant's arguments filed 7/7/26 have been fully considered but they are not persuasive.
Regarding the interpretation, Applicant argues “having” is meant to be a “clear” drafting choice of open language. This does not point to any specific deficiency in the interpretation. The term “having” is not clear and MPEP §2111.03(IV) explicitly uses “having” as an example of claim language that must be evaluated and could mean either open or closed language; “the term ‘having’ in transitional phrase ‘does not create a presumption that the body of the claim is open’”. The examiner notes that the use of “comprising” rather than “having” would be sufficient to clearly indicate open language.
Regarding the drawing objection, Applicant argues color drawings have been submitted with a corresponding petition to accept these drawings. This accurately reflects the facts, yet a granted petition is necessary to accept the color drawings. As of the writing of this office action, the petition has not been decided. As noted above, should the petition be granted, the objection will be withdrawn.
Regarding the use of “optionally”, Applicant argues the ordinary definition of “optional” is “not required”. While generally true in non-patent uses, the MPEP still instructs examiners to evaluate how the phrase is used (MPEP §2173.05(h)(II)). Applicant argues that “optionally” is not per se indefinite. The Examiner agrees but no portion of the rejection suggested the phrase was being per se rejected; rather, the rejection articulated the reasoning for the rejection. Applicant argues that the situation “A, B, and optionally C” is acceptable per the MPEP. This is not persuasive because this is not the fact pattern of the instant claims. The phrasing in the MPEP denotes an additional, optional element (C), which was at issue in Cordova. Here, the phrasing to closer to “A, optionally A’ or A””, i.e., the relationship is one of a recitation of a broad genus followed by “optionally” narrowing that genus. The term “optionally” may introduce an entirely new feature such as in Cordova, in which case the use is generally acceptable. Here, the genus is required while the “options” are examples of this genus.
Applicant argues that other patents use “optionally” and so the phrase is not inherently indefinite. Again, the Examiner never suggested the phrase was inherently indefinite. The fact that “optionally” was definite in other patents provides no specific reasoning as to why the phrase is definite in this case nor does it point to any specific deficiency in the Examiner’s rejection. Each application is prosecuted on its own merits.
However, Applicant states that these “limitations” need not be present. This supports the Examiner’s conclusion that—in this specific case—the use of “optionally” is used to merely provide examples of the genus. This is not in contravention of the “A, B, and optionally C” format nor is this a conclusion that the phrase “optionally” cannot possibly be used in a claim. Rather, this is a conclusion based on the facts of record and articulated herein. Further note that this objection is not made over claim 93. Applicant has removed the examples of ALK from claim 93 and properly provided them as limitations in new claim 97.
Regarding the written description rejection, Applicant argues that claims 1, 21, 41, and 44 have been amended to incorporate the limitations of claim 13. This is persuasive and the rejection of those claims have been withdrawn. Previous claims 57, 87, and 92 were also rejected and depended from rejected claims 1 and 44. Claims 57, 87, and 92 have been amended to be independent claims. Rather than incorporating the limitations of previous claim 13, these claims incorporate the previously rejected language of claims 1 and 44.
Applicant argues that these claims satisfy the written description rejection because the specification does not merely recite a desired result but discloses multiple representative antibodies. The previous (and current) rejection addressed this: there is no conserved, required structure in these claims and the number of “multiple representative antibodies” is three, which is insufficient for the reasons of record. Applicant argues the ALK antibodies are demonstrated in different formats and different uses, but this does not criticize nor point to any specific deficiency in the rejection. Applicant argues the specification conveys possession of the claimed methods and so should be considered to meet the written description requirement even if the composition claims to an antibody genera “remain at issue”. This does not articulate any specific reason that the antibodies—which are required for practicing the methods—meets the written description rejection in light of the findings of the examiner presented in the rejection. Note that while the claims are methods, the composition used to practice those methods must still meet the written description requirement. Amgen makes clear that there is no special written description requirement for a particular class of compounds and the same written description requirement applies, while the Court in Rochester (358 F.3d 916) clearly noted that decisions in composition of matter cases apply to methods. Thus, where the genus of claimed antibodies fails to meet the written description requirement as indicated in the rejection, the method of using that same genus also fails.
Allowable Subject Matter
Reasons for allowance are found in the action mailed 4/9/26.
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.
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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