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 election without traverse filed May 14, 2026, is acknowledged and has been entered. Applicant has elected Group I. Applicant has elected the species of an antigen binding polypeptide complex having two polypeptides, where the first polypeptide has the structure VL1-L1-VL2-L2-VH2-L3-VH1-Fc and the second polypeptide the structure VL3-L5-VH3-Fc. Applicant submits that claims 108, 116, 120, 123, 124 and 127 read on this species within Group I.
The amendment filed May 14, 2026, is acknowledged and has been entered. Claims 117-119, 125, 126 and 128 have been canceled.
Claims 108-116, 120-124, 127, 129 and 130 are pending. Claims 109-115, 121-122, 129 and 130 are withdrawn from further consideration, as being drawn to non-elected invention or species of invention. Claims 108, 116, 120, 123, 124 and 127 are under consideration.
Information Disclosure Statement
The information disclosure statements have been considered.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 123 and 124 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. In this case, claim 123 recites “An antibody or antigen binding fragment thereof comprising the antigen binding polypeptide complex of claim 108”, while the specification discloses that the “term “antibody” includes, without limitation, a glycoprotein immunoglobulin which binds specifically to an antigen” (see ¶ [0090] such that one would understand “the antigen binding polypeptide complex of claim 108” to be an antibody. Then the term “antigen binding fragment" of an antibody is defined as “one or more fragments or portions of an antibody that retain the ability to bind specifically to the antigen bound by the whole antibody” (see ¶ [0093]), but here the antigen binding fragment thereof comprises the antigen binding polypeptide complex of claim 108 and the antigen binding polypeptide complex is an antibody, such that the term “antigen binding fragment" fails to further limit “the antigen binding polypeptide complex of claim 108”. Then with respect to claim 124, which recites “the antibody or antigen binding fragment thereof of claim 123, wherein the antigen binding fragment is a Fab, scFab, Fab', F(ab')2, Fv, or scFv”, while the claims still includes the antibody of claims 123 that fials to further limit claim 108, as set forth above, the limitation “wherein the antigen binding fragment is a Fab, scFab, Fab', F(ab')2, Fv, or scFv” fails to include all the limitations of the claim upon which it depends because a Fab, scFab, Fab', F(ab')2, Fv, or scFv do not comprise the antigen binding polypeptide complex of claim 108. This is the case because the antigen binding polypeptide complex of claim 108 requires an Fc while none of a Fab, scFab, Fab', F(ab')2, Fv, or scFv comprise an Fc.
It is suggested that claims 123 and 124 be canceled to obviate the rejection.
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 108, 116, 120, 123, 124 and 127 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.
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991).
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or it may be satisfied by the disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. “Functional” terminology may be used “when the art has established a correlation between structure and function” but “merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing one has invented a genus and not just a species. Ariad Pharmaceuticals Inc. v. Eli Lilly & Co., 598 F3d 1336, 94 USPQ2d 1161, 1171 (Fed Cir. 2010).
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). “[A] sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Ariad, 598 F.3d at 1350 (quoting Eli Lilly, 119 F.3d at 1568-69). A “representative number of species” means that those species that are adequately described are representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. The “structural features common to the members of the genus” needed for one of skill in the art to ‘visualize or recognize’ the members of the genus takes into account the state of the art at the time of the invention. For example, the Federal Circuit has found that possession of a mouse antibody heavy and light chain variable regions provides a structural "stepping stone" to the corresponding chimeric antibody, but not to human antibodies. Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875 (Fed. Cir. 2011).
The claimed invention. The nature and scope of the claimed invention at issue is the antigen-binding polypeptide complex of claim 108, which comprises variable regions of VL1, VL2, VL3, VH1, VH2, and VH3, which as set forth in claim 116 each bind to different antigens by themselves. Accordingly, claim 116 requires antigen binding by a VL alone or a VH alone. Therefore, it is apparent that the variable regions of VL1, VL2, VL3, VH1, VH2, and VH3 in claim 108 also encompass individual light chain variable domains that bind one antigen alone and individual heavy chain variable domains that bind a different antigen alone. The other dependent claims do not define antigen binding, so they also include such antigen binding activities. Accordingly, the claims do not require that corresponding pairs of VH/VL domains (e.g., VH1/VL1, VH2/VL2, VH3/VL3) bind to the same antigen. The rejected claims fail to satisfy the written description requirement because neither Applicant's disclosure nor the prior art support the notion that random combinations of VH/VL domains against mismatched antigens would be expected to yield a protein having a functional antigen-binding site that performs the required function of specifically binding to one antigen via a VL domain and the VH domain binding a different antigen.
State 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 comprises three CDRs (or hypervariable regions) that provide the majority of the contact residues for the binding of the antibody to its target epitope. See Almagro (Frontiers in Immunology (2018) 8: 1751), “The IgG Molecule” (page 3) and Figure 1. Sela-Culang (Frontiers in Immunology (2013) 4: 302) 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). 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).
Scope of species disclosed in original specification. The disclosure illustrates exemplary trispecific constructs comprising VH/VL pairs having specificity for CD3, CD28 and CD38 where a single VH/VL pair binds to CD3, a single VH/VL pair binds to CD28 and a single VH/VL pair binds to CD38 (see examples 1-3, pages 377-378). The specification does not disclose a single VL that binds an antigen paired with a single VH that binds a different antigen.
MPEP § 2163 states that a “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. While the disclosure does enumerate several exemplary embodiments wherein a single VH/VL pair binds to a single antigen, these embodiments are not representative of a VH/VL pair where the VL binds one antigen and the VH binds a different antigen because the art and the specification provide evidence that generally the VH/VL pair structure together is required for antigen-binding.
In the absence of a representative number of species, the written description requirement for a claimed genus may be satisfied by disclosure of relevant, identifying characteristics; i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. Based on the disclosure, Applicant is not in possession of antigen binding polypeptide complexes in which members of each respective VH/VL pairing bind to separate antigens, nor does Applicant provide a showing that such pairings would yield a functional protein that specifically binds to either antigen as claimed.
Conclusion. For the reasons presented above, one of skill in the art would not know which of the countless other antigen-binding polypeptide complexes encompassed by the highly general structural requirements of the claims would also possess the required functional activity. Given the lack of shared structural properties that provide the claimed binding activity, the limited number of species described, and the fact that the species that were described cannot be considered representative of the broad genus, the Applicant did not possess the full genus of antigen-binding polypeptide complexes as broadly claimed at the time the application was filed.
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.
Claims 108, 120, 123, 124 and 127 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Tesar et al (WO 2019/198051 A2, IDS).
Claims 108, 120, 123 and 124 are herein drawn to an antigen binding polypeptide complex having two polypeptides, where the first polypeptide has the structure VL1-L1-VL2-L2-VH2-L3-VH1-Fc and the second polypeptide the structure VL3-L5-VH3-Fc. This structure is illustrated in Figure 1A (copied below), with the specification (see ¶ [0039] referring to the left arm of the antibody as an scFv-Fc polypeptide:
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Claim 127 is herein drawn to a composition comprising said antigen binding polypeptide complex, and a pharmaceutically acceptable carrier.
With respect to claims 108, 120, 123 and 124, Tesar et al disclose an antigen binding polypeptide complex having two polypeptides, where the first polypeptide has the structure VL1-L1-VL2-L2-VH2-L3-VH1-Fc and the second polypeptide the structure VL3-L5-VH3-Fc, wherein the Fc region comprises at least one knob-in hole modification. The structure of such a molecule is given in Figure 4 (copied below). The specification sets forth that the structure of the first polypeptide can be a single chain diabody with a VL-linker1-VL-linker3-VH-linker2-VH structure, linked to an Fc region with a knob-in-hole modification and the second polypeptide can be an scFv with a VL-linker-VH structure linked to an Fc region with a knob-in-hole modification (see entire document, e.g., pages 5, 23, 24, 38, 43, 45, 90, 94-95 and 134, Figures and claims).
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With respect to claim 127, Tesar et al disclose a composition comprising said antigen binding polypeptide complex, and a pharmaceutically acceptable carrier (see e.g., pages 72 and 78 and claims).
Therefore, Tesar et al is deemed to anticipate the instant claims absent a showing otherwise.
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 and can normally be reached Monday through Friday.
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.
Respectfully,
Brad Duffy
571-272-9935
/Brad Duffy/
Primary Examiner, Art Unit 1643
August 22, 2026
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