Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
DETAILED ACTION
Applicant's election with traverse of Group I, claims 1-13, in the reply filed on 07/20/2026 is acknowledged. The traversal is on the ground(s) that “searching the non-elected claims would not present an undue burden.” This is not found persuasive, because in the Requirement for Restriction/Election, dated 01/20/2026, two groups were articulated. These groups have materially different designs, because the invention of Group II requires the diversification of specific Lib1 or Lib2 position CDR residues. Furthermore, the inventions as claimed do not encompass overlapping subject matter and there is nothing of record to show them to be obvious variants. Furthermore the examination of both groups would impose a serious search and/or examination burden if restriction were not required, at least because the examination of both groups would require a different field of search (e.g., searching different classes/subclasses or electronic resources, or employing different search strategies or search queries). The requirement is still deemed proper and is therefore made FINAL.
Claims 1-20 are pending.
Claims 14-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 01/20/2026.
Claims 1-13 are under examination on the merits.
Claim Rejections
35 U.S.C 112, First Paragraph
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 1-13 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The purpose of the written description requirement is to ensure that the inventor had possession, at the time the invention was made, of the specific subject matter claimed. To satisfy the written description requirement, a patent 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. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.
The claims are directed to an antibody or functional fragment thereof comprising at least one variable binding domain consisting of a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein said binding domain comprises two paratopes for two unrelated epitopes, wherein (i) binding of each paratope to its epitope does not prevent the simultaneous binding of the other paratope to its respective epitope, and wherein (ii) both paratopes comprise at least one residue from at least one VH CDR and at least one residue from at least one VL CDR. At Examples 2 and 3, Applicant discloses an example of the claimed antibody or functional fragment thereof, specifically, a bispecific antibody capable of binding MBP and GST. At Example 8, Applicant discloses another example of the claimed antibody or functional fragment thereof, specifically, a bispecific antibody capable of binding VEGF and IL-6 (the VH6L clone), and at Example 9, Applicant discloses a bispecific antibody capable of binding GMCSF and IL-6 (the GH6L clone). However, one skilled in the art would appreciate that the claimed antibody or functional fragment thereof represents a large genus of antibodies with different paratope sequences capable of binding a wide range of antigens, and one skilled in the art would reason that said different paratope sequences comprise different VH and VL CDR amino acid sequences. As such Applicant is claiming a broad genus of antibodies but only appears to be in possession of three antibodies comprised within said genus, specifically, 1) a bispecific antibody capable of binding MBP and GST, 2) a bispecific antibody capable of binding VEGF and IL-6 (the VH6L clone), and 3) a bispecific antibody capable of binding GMCSF and IL-6 (the GH6L clone). Although one skilled in the art could screen for heavy and light chain variable domains that form an antigen-binding domain that comprises two paratopes for two unrelated epitopes, wherein (i) binding of each paratope to its epitope does not prevent the simultaneous binding of the other paratope to its respective epitope, and wherein (ii) both paratopes comprise at least one residue from at least one VH CDR and at least one residue from at least one VL CDR, absent empirical determination, one skilled in the art would be unable to envision which heavy and light variable domain sequences should be paired such that the resultant antigen-binding domain comprises two paratopes for two unrelated epitopes, wherein (i) binding of each paratope to its epitope does not prevent the simultaneous binding of the other paratope to its respective epitope, and wherein (ii) both paratopes comprise at least one residue from at least one VH CDR and at least one residue from at least one VL CDR. Accordingly the specification does not provide adequate written description for the entire claimed genus.
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, reduction to drawings, or 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. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
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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. In the instant case, as indicated above, Applicant has adequately described three antibodies comprised within said genus, specifically, 1) a bispecific antibody capable of binding MBP and GST, 2) a bispecific antibody capable of binding VEGF and IL-6 (the VH6L clone), and 3) a bispecific antibody capable of binding GMCSF and IL-6 (the GH6L clone); however given the large breadth of the genus claimed as well as the high level of unpredictability in the antibody arts, it is submitted that the adequate description of said three antibody species comprised within the genus claimed is not sufficient to adequately describe the entire genus. Also Applicant has not sufficiently described the claimed genus by disclosing functional characteristics coupled with a correlation between function and structure, because even though Applicant has provided a function for the genus of antibodies claimed, specifically the ability to bind multiple antigens, Applicant has not provided a structure that correlates with said function. Given that antibodies are 1) known to bind chemically diverse antigens, including proteins, lipids, and carbohydrates and 2) known to bind protein antigens with a wide range of amino acid sequences, one skilled in the art would appreciate that the paratopes comprised within the claimed genus of antibodies would accordingly comprise a wide range of amino acid sequences that correspond with the ability to bind said antigens.
Given the lack of particularity with which the antibodies are described in the specification, it is submitted that the skilled artisan could not immediately envision, recognize, or distinguish at least most of the members of the claimed genus to which the claims are directed, and therefore, the specification would not reasonably convey to the skilled artisan that Applicant had possession of the claimed invention at the time the application was filed.
35 U.S.C. 102(b)
The following is a quotation of the appropriate paragraphs of pre-AIA 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 –
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
Claims 1, 2, and 5-13 are rejected under pre-AIA 35 U.S.C. 102(b) as being anticipated by Fuh et al. (WO 2008/027236, international publication date: 03/06/2008, in IDS from 07/20/2026), as evidenced by Bostrom et al. (Science, 323, 1610-1614, 2009, in IDS from 07/20/2026).
Fuh et al. disclose a method of producing a bispecific antibody comprising (1) diversifying the amino acid sequence of a light chain variable domain (VL) of an antibody, wherein prior to the diversification, the antibody comprised a VL and a heavy chain variable domain (VH) capable of binding to a first epitope and (2) selecting a diversified antibody capable of binding to the first epitope and a second epitope, see p. 2. At p. 3, Fuh et al. disclose that “[a]ccording to one embodiment, the selection step for binding to the first epitope or the selection for binding to the second epitope occurs in the presence of both diversified [VL] and [VH]. According to another embodiment, the diversified [VL] and [VH] can bind the first epitope and second epitope simultaneously. In an alternative embodiment, the diversified [VL] and [VH] bind the first epitope and second epitope mutually exclusively. In one embodiment, the first epitope is from one biological molecule and the second epitope is from the same biological molecule. In another embodiment, the first epitope is from one biological molecule and the second epitope is from a second biological molecule. According to one embodiment the first biological molecule and the second biological molecule are structurally unsimilar (emphasis added).” At Example 1, Fuh et al. teach that diversified antigen-binding regions may be diversified human antigen-binding regions, such as a human Fab.
At Example 1, Fuh et al. discuss the production of one such antibody, bH1, which is a bispecific antibody capable of binding both VEGF and HER2. Figure 35C depicts the binding of VEGF (in dark shading) and HER2 (white) to the CDR loops of bH1. Based on Figure 35C, it appears that VEGF contacts amino acid residues in each of the six heavy and light chain CDRs of bH1, although CDR-L2 appears to minimally contact VEGF, and it also appears that there are amino acid residues in each of the six heavy and light chain CDRs of bH1 that contact HER2. The bispecific antibody of Fuh et al. reads on a bispecific antibody or functional fragment thereof comprising at least one variable binding domain consisting of a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein said binding domain comprises two paratopes for two unrelated epitopes, wherein (i) binding of each paratope to its epitope does not prevent the simultaneous binding of the other paratope to its respective epitope, and wherein (ii) both paratopes comprise at least one residue from at least one VH CDR and at least one residue from at least one VL CDR, thus meeting the limitations of claims 1 and 2.
With respect to claim 5, as indicated above, Fuh et al. disclose diversified, bispecific antibodies, wherein each paratope comprises at least some residues of each of the heavy and light chain CDRs.
With respect to claim 6, the limitations of this claim are met by Fuh et al., because as indicated above, at Example 1, Fuh et al. disclose that diversified antigen-binding regions may be diversified human antigen-binding regions, such as a human Fab. Also at p. 13 and 14, Fuh et al. indicate that the antibodies of the invention may be monoclonal antibodies that may be prepared via the use of various technologies, including technologies for producing human antibodies.
With respect to claims 7 and 8, Fuh et al. disclose that antibodies of the invention may be prepared via the diversification of the Herceptin antibody, and as evidenced at p. 1610, third column, of Bostrom et al., Herceptin comprises framework regions that belong to subtypes VH3 and Vkappa1 of the human antibody repertiore.
With respect to claim 9, Fuh et al. disclose that bispecific antibodies of the invention may exist in IgG form, and Fuh et al. also teach that the bispecific antibodies of the invention may exist in a variety of other forms, including antibody fragments, which may include Fab fragments and single chain antibody molecules, see p. 4, 11, and 15.
With respect to claims 10-13, Fuh et al. disclose that the antibodies of the invention may be prepared by cloning nucleic acids encoding the VH and VL domains into a vector for Fab expression in E.coli or cloning nucleic acids encoding VH and VL domains into a vector for transient human IgG expression in mammalian cells, followed by expressing said VH and VL domains in each host cell, culturing said host cells, and purifying said antibodies, see p. 58.
Accordingly all of the limitations of claims 1, 2, and 5-13 are met by Fuh et al., as evidenced by Bostrom et al.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NELSON B MOSELEY II whose telephone number is (571)272-6221. The examiner can normally be reached on M-F, 9:00-6:00 EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis, can be reached at 571-270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642
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