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
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 allowance or after an Office action under Ex Parte Quayle, 25 USPQ 74, 453 O.G. 213 (Comm'r Pat. 1935). 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, prosecution in this application has been reopened pursuant to 37 CFR 1.114. Applicant's submission filed on 5/22/26 has been entered.
Claims 1, 2, 4-5, 8, 16, 21, 24-25, and 35 are pending and under examination.
Notice
The Examiner’s amendments in the notice of allowance mailed 2/24/26 have not been entered because of the RCE. While the instant office action necessarily contains objections/rejections to address these issues, the Examiner confirms that the previously agreed upon amendments would correct those deficiencies. Note that the written description rejection is new as necessitated by the new information provided on the IDS.
Claim Objections
Claim 2 is objected to because of the following informalities: line 3 states “any of SEQ ID NO: 24”. Where there is only one item in a list, the phrase “any of” is not appropriate. 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.
Claims 5 and 8 is 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 5 recites the limitation "the isolated antibody…of claim 0[-4]". There is insufficient antecedent basis for this limitation in the claim. There is no claim 0 and no means to determine what the limitations of claim 0 are. Further, it is unclear what “-4” is meant to imply. The claim has removed the phrase “any of” and so it does not appear to be a multiple dependent claim, but it is unclear what else “0[-4]” could mean. Note that the brackets around -4 are underlined indicated Applicant intends the brackets are meant to be added rather than deleting “-4”.
Similarly, claim 8 recites “the isolated antibody…of claim 1[-7]”. As above, the brackets are underlined indicating these brackets are meant to be added to the claim rather than the brackets denoting deletion of “-7”. However, also as above, it is unclear what claim -7 is meant to imply, there is no claim -7, and the phrase is in the singular so the claim is not a multiple dependent claim.
Therefore, claims 5 and 8 are indefinite. For examination purposes, the claims are treated as depending from claim 1.
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.
Claim 35 is 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 35 is directed to any antibody or fragment thereof that binds one or more Fzd receptors. As such, this limitation 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.”
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 (Fzd) 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 IDS 7/24/23 NPL 344) 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. 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”.
One means of meeting the written description requirement is through providing 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 this case, the specification does not correlate any particular shared structure within the claimed function nor is there reason to expect such a conserved structure because a similar structure may bind wholly different targets (Kussie) while disparate structures may still bind the same target (Abbvie).
In a second way, the specification might provide a representative number of species for the claimed genus that would convey to the artisan possession of the whole genus. The specification references US 62/607877 on p.18. This document has not been cited on an IDS. If this document is meant to support a claim under §112a, then the subject matter constitutes “essential material” (37 CFR 1.57) but incorporation by reference to an unpublished application is improper (37 CFR 1.57(d); MPEP 608.01(p)(I)(A)(2)). As such, this disclosure in unpublished 62/607877 cannot be considered to support the written description requirement.
The specification also discloses antibody OMP-18R5 (paragraph 19). This antibody comprises six CDRs. The specification also discloses a number of other available antibodies in the paragraph spanning p.19-20. Generally, this would be considered a sufficient number of species to support the genus.
However, page 19 also suggests that Fzd antibodies include, e.g., VHH and sdABs. However, no examples of any single domain antibodies binding Fzd are provided. VHHs are unique antibodies that only require three CDRs and are not generated merely by using only the heavy or light chain of a traditional antibody.
Further, Applicant has submitted several documents on the IDS. MS&D exhibit 1003 Kahn (X1003K) states that these Fzd antibodies may bind any number of the 10 Fzd receptors or even multiple such receptors at once (p. 4), which is true of the instant claim as well (“binds one or more Frizzled (Fzd) receptors”). The instant claims, like the claims addressed in X1003, are Fzd-LRP multispecific antibodies that include binding LRP5, LRP6, and all 10 Fzd receptors at once as well as any subcombination thereof and acts as a Wnt agonist. X1003 states there are no species binding Fzd3, Fzd6, or Fzd10. While the instant specification refers to Pan-Fzd binding antibodies, there is no clear evidence that antibodies which bind specific combinations are possessed by Applicant. These opinions appear to be echoed in MS&D exhibit 1002 Kahn (X1002K) and MS&D exhibit 1002 McDonnel (X1002M).
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of 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 [he or she] invented what is claimed.” (See Vas-Cath at page 1116). As discussed above, the artisan cannot envision the detailed chemical structure of the encompassed genus of polypeptides, 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 compound 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.
MPEP §2163 states “information which is well known in the art need not be described in detail in the specification…however, sufficient information must be provided to show that the inventor had possession of the invention as claimed”.
While the specification appears to disclose a number of antibody species, this paragraph does not explicitly indicate that these antibodies represent the genus of antibodies that bind multiple Fzds and the various subcombinations of Fzd receptors.
Therefore, claim 35 does not meet the written description requirement.
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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