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 .
DETAILED ACTION
The species election without traverse filed November 5, 2025, is acknowledged. However, after further consideration the species requirement has been withdrawn because the CDR sequences of claim 36 are free of the prior art.
Claims 36-51 are pending and are under examination.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
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 36-51 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 a nucleic acid encoding the heavy chain variable region and the light chain variable region of an antibody or antigen binding fragment thereof that binds to canine PD-L1, wherein the nucleic acid comprises:
a) a first nucleic acid sequence that encodes a heavy chain variable region comprising a set of three heavy chain CDRs comprising the amino acid sequences of SEQ ID NO: 13, SEQ ID NO: 14, and SEQ ID NO: 15, and
b) a second nucleic acid sequence that encodes a light chain variable region comprising a set of three light chain CDRs comprising the amino acid sequences of SEQ ID NO: 16, SEQ ID NO: 17, and SEQ ID NO: 18,
and while be enabling for a composition that comprises a first nucleic acid that encodes the heavy chain variable region of an antibody or antigen binding fragment thereof that binds to canine PD-L1 and a second nucleic acid that encodes the light chain variable region of an antibody or antigen binding fragment thereof that binds to canine PD-L1, wherein:
a) the first nucleic acid comprises a nucleic acid sequence that encodes a heavy chain variable region comprising a set of three heavy chain CDRs comprising the amino acid sequences of SEQ ID NO: 13, SEQ ID NO: 14, and SEQ ID NO: 15, and
b) the second nucleic acid comprises a nucleic acid sequence that encodes a light chain variable region comprising a set of three light chain CDRs comprising the amino acid sequences of SEQ ID NO: 16, SEQ ID NO: 17, and SEQ ID NO: 18,
does not reasonably provide enablement for the full scope of the claimed nucleic acids such as a nucleic acid encoding just a set of three heavy chain CDRs comprising the amino acid sequences of SEQ ID NO: 13, SEQ ID NO: 14, and SEQ ID NO: 15 or a nucleic acid encoding just a set of three light chain CDRs comprising the amino acid sequences of SEQ ID NO: 16, SEQ ID NO: 17, and SEQ ID NO: 18. 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.
The amount of guidance, direction, and exemplification disclosed in the specification, as filed, would not be sufficient to enable the skilled artisan to use the claimed invention at the time the application was filed without undue experimentation. MPEP § 2164.01 states: “The standard for determining whether the specification meets the enablement requirement was cast in the Supreme Court decision of Mineral Separation v. Hyde, 242 U.S. 261, 270 (1916) which postured the question: is the experimentation needed to practice the invention undue or unreasonable? That standard is still the one to be applied. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). Accordingly, even though the statute does not use the term "undue experimentation," it has been interpreted to require that the claimed invention be enabled so that any person skilled in the art can make and use the invention without undue experimentation. In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404 (Fed. Cir. 1988).”
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue”. These factors, which have been outlined in the Federal Circuit decision of In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), include, but are not limited to, the nature of the invention, the state of the prior art, the relative skill of those in the art, the amount of direction or guidance disclosed in the specification, the presence or absence of working examples, the predictability or unpredictability of the art, the breadth of the claims, and the quantity of experimentation which would be required in order to practice the invention as claimed. See also Ex parte Forman, 230 USPQ 546 (BPAI 1986).
Nature of the invention / Breadth of the claims
The nature of the claims at issue broadly, but reasonably encompass a nucleic acid encoding just a set of three heavy chain CDRs comprising the amino acid sequences of SEQ ID NO: 13, SEQ ID NO: 14, and SEQ ID NO: 15 (see claim 36) or a nucleic acid encoding just a set of three light chain CDRs comprising the amino acid sequences of SEQ ID NO: 16, SEQ ID NO: 17, and SEQ ID NO: 18 (see claim 48). Dependent claims 37-39, 44-47 and 51 also encompass nucleic acids and vectors that comprise nucleic acids which encode three CDRs without variable region or other CDR structure. Then dependent claims 40-43 and 49-50 recite nucleic acids and vectors that either encode just a heavy chain (see claims 40-43) or just a light chain (see claims 49-50).
State of the prior art / Predictability of the prior art
It is well established in the art that the formation of an intact antigen-binding site in an antibody usually requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs (or hypervariable regions), which provide structure of the antigen binding site and the majority of the contact residues for the binding of the antibody to its target epitope (Almagro & Fransson, Frontiers in Bioscience 2008; 13:1619-33; entire document, specifically note Section 3 “Antibody Structure and the Antigen Binding Site” and Figure 1,). Through analysis of different methods for humanizing antibodies, Almagro et al. shows that all of the six CDRs of the heavy and light chain, in their proper order of CDR 1 , then 2, then 3, and in the context of framework sequences which maintain their required conformation are generally required to produce a humanized antibody in which the heavy and light chains associate to form an antigen-binding region that binds the same antigen as the parental rodent antibody (entire document, specifically note “Section 4”). Sela-Culang (Frontiers in Immunology (2013) 4: 302, pages 1-13) further teaches, “A major focus in analyzing the structural basis for [antigen] recognition has been in identifying the exact boundaries of the CDRs in a given [antibody]. It is a common practice to identify paratopes through the identification of CDRs” (page 3, left column, “CDRs Identification”).
Although the prior art teaches some understanding of the structural basis of antigen-antibody recognition, it is aptly noted that the art is characterized by a high level of unpredictability, since the skilled artisan still cannot accurately and reliably predict the consequences of amino acid substitutions, insertions, and deletions in the antigen-binding domains. Ni (The Protein Journal (2024) 43: 683-696) teaches, “Mutations, even one mutation, introduced in the CDRs through [somatic hypermutation] can change the binding properties and repertoire of antibodies. However, how just one-point mutation can dramatically change the recognition profiles of the antibody is still unclear” (Introduction). Furthermore, while affinity maturation techniques can result in differences in the CDRs of the antibody compared to its parental antibody, those techniques involve trial-and-error testing and the changes that maintain or improve affinity are not predictable a priori (Almagro et al (Frontiers in Immunology, 2018; 8:article 1751, pages 1-19), pages 3 and 6-7).
Therefore, it is expected that all 6 CDRs need to be grafted into antibody framework regions to retain the requisite specificity and functionality of the parent antibody.
Working examples / Guidance in the specification
The specification discloses making an antibody (4FD9) that binds canine PD-L1, wherein the antibody comprises a heavy chain variable region comprising a CDR-1H comprising SEQ ID NO:13; a heavy chain CDR-2H comprising SEQ ID NO:14; a heavy chain CDR-3H comprising SEQ ID NO:15; and a light chain variable region comprising a light chain CDR-1L comprising SEQ ID NO: 16; a light chain CDR-2L comprising SEQ ID NO: 15; and a light chain CDR-3L comprising SEQ ID NO: 18 binds PD-L1 (see page 72) and nucleic acids that encode said antibody (see pages 27 and 28). It does not characterize any mutations or variants that give specific binding to PD-L1. It does not disclose any uses for a nucleic acid encoding just a set of three heavy chain CDRs comprising the amino acid sequences of SEQ ID NO: 13, SEQ ID NO: 14, and SEQ ID NO: 15 or a nucleic acid encoding just a set of three light chain CDRs comprising the amino acid sequences of SEQ ID NO: 16, SEQ ID NO: 17, and SEQ ID NO: 18, nor does it disclose a specific use for just a nucleic acid encoding just a heavy chain or just a light chain.
Quantity of experimentation/Conclusion
As set forth above a skill artisan cannot predict that less than all 6 CDRs in an antibody structure will have any function, and generally all 6 CDRs in an antibody structure are needed for antigen binding, so one of skill in the art would be subject to undue experimentation to identify uses for the full scope of the claimed nucleic acids. Notably, a nucleic acid encoding just three heavy chain CDRs would not express a protein with the structure of the 4F9 antibody disclosed in the specification, such that one would need to identify a use for such a nucleic acid, which would require undue experimentation. Similarly, a nucleic acid encoding just three light chain CDRs, just a heavy chain or just a light chain also would not express any protein with the structure of the 4F9 antibody disclosed in the specification, such that one would need to identify a use for such nucleic acids, which would require undue experimentation
Applicant is reminded that reasonable correlation must exist between the scope of the claims and scope of enablement set forth.
In deciding In re Fisher, 166 USPQ 18, 24 (CCPA 1970), the Court indicated the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. “Tossing out the mere germ of an idea does not constitute enabling disclosure. While every aspect of a generic claim certainly need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public to understand and carry out the invention.” Genentech Inc. v. Novo Nordisk A/S, 42 USPQ2d 1001, 1005 (CA FC 1997).
Thus, the overly broad scope of the claims would merely serve as an invitation to one skilled in the art to identify uses for the claimed nucleic acids.
In conclusion, upon careful and full consideration of the factors used to determine whether undue experimentation is required, in accordance with the Federal Circuit decision of In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404 (Fed. Cir. 1988), the amount of guidance, direction, and exemplification disclosed in the specification, as filed, is not deemed sufficient to have enabled the skilled artisan to make and/or use the claimed invention at the time the application was filed without undue and/or unreasonable experimentation.
It is suggested that the rejection could be obviated by amending the claims appropriately to be drawn to enabled subject matter as set forth in the introduction of this rejection.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Brad Duffy whose telephone number is (571) 272-9935. The examiner works a flexible schedule.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Julie Wu can be reached on (571) 272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Respectfully,
Brad Duffy
571-272-9935
/Brad Duffy/
Primary Examiner, Art Unit 1643
February 20, 2026