DETAILED ACTION
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 .
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 final rejection. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 2/06/2026 has been entered.
Applicant’s amendment, filed on 2/06/2026, is acknowledged.
Claims 1-9, 12, 16-18, 20, 21, 26, and 27 are cancelled.
Claims 10, 11, 13-15, 19, 22-25, and 28-40 are currently pending and are under examination.
Claims 15, 31, 37 are independent claims.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 2/06/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner in its entirety.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
¶[0075] lists linker amino acid sequences of four or greater residues in length.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specification
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed.
The use of the terms: GenomONE™ (¶[00103]), Ex Cell™ (¶[00103]), MabSelect™ (¶[00103], [00108]) HiTrap® (¶[00108]), QUANTI-Luc™ (¶[00205]), which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore, the terms should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 10, 11, 13-15, 19, 22-25, 28-30, and 33-35 are objected to because of the following:
Claims 10, 11, 13, and 14 are objected to under 37 CFR 1.75(c) because it is improper dependent claim since it fails to refer back to an earlier claim. Rather claim 10, 11, 13, and 14 refer back to a proceeding claim 15. 37 CFR 1.75(c) states: (c) One or more claims may be presented in dependent form, referring back to and further limiting another claim or claims in the same application.
Claim 15 is objected to because the claim recites “…and CDRs LI, L2…” and should most likely recite “and CDRs L1, L2…” to resolve a minor typographical error. Dependent claims 10, 11, 13, 14, 19, 22-25, 28-30, and 33-35 do not resolve this issue and are also objected to.
Claim 24 is additionally objected to because the claim currently recites “…and the scFv has an amino acid comprising SEQ ID NO: 22 or 122” and should most likely recite “and the scFv has an amino acid sequence comprising SEQ ID NO: 22 or 122” to resolve a minor typographical error.
Claim 25 is additionally objected to because the claim currently recites “…wherein the first binding site specifically binding to EGFR” and should most likely recite “wherein the first binding site specifically binds to EGFR” to resolve a minor typographical error.
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 15, 19, 37, and 40 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 claims contain 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 inventors, at the time the application was filed, had possession of the claimed invention.
Regarding claims 15 and 19:
Claims 15 and 19 encompass a genus of bispecific antibodies comprising a first 13 and 14 encompass bispecific antibodies with a broad genus of first binding sites with no recited structure and the recited function of “binding to an antigen on a cancer cell” (claim 15) or “binds to CD33” (claim 19).
However, there does not appear to be an adequate written description in the specification as-filed of the essential structural feature that provides the recited functions of “binding to an antigen on a cancer cell” (claim 15) or “binds to CD33” (claim 19). The Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112(a) or U.S.C 112, ¶ 1 "Written Description" Requirement make clear 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, 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 genus.
The specification discloses one bispecific antibody comprising a first binding site that binds to the CD33 cancer antigen (Example 2, ¶[00109], and Fig. 2).
The specification fails to provide adequate written description support for a bispecific antibodies comprising a broad genus of first binding sites with no recited structure having the desired functional properties required to practice the claimed functions of “binding to an antigen on a cancer cell” (claim 15) or “binds to CD33” (claim 19).
The claims are not supported by a description that satisfies 35 U.S.C. § 112(a) or 35 U.S.C. § 112, first paragraph. "[T]he test for sufficiency [ of the written description] is whether the disclosure of the application relied upon reasonably conveys to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date." Ariad Phanns., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en bane).
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." Id. at 1350. "[A]n adequate written description requires a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials." Id.
"[F]unctional claim language can meet the written description requirement when the art has established a correlation between structure and function." Id. "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 that one has invented a genus and not just a species." Id.
"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" (AbbVie, 759 F.3d at 1297, reiterating Eli Lilly, 119 F.3d at 1568-69) (emphasis added).
The specification only one example of a bispecific antibody with a first binding site with the functions of “binding to an antigen on a cancer cell” (claim 15) or “binds to CD33” (claim 19), which is BS824 (¶[00109]). This first binding site has a defined structure (i.e., amino acid sequence especially in the 6 CDR regions required for antigen binding), while instant claims 15 and 19 recite broad genera of millions to billions of different antibody structures with the recited functions.
With respect to representative number of species, see AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc. (Fed. Cir. 2014). Also, see MPEP 2163 Il(A)(3)(a))(ii):
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. 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. See Abb Vie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus.").
Satisfactory disclosure of a "representative number" depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are "representative of the full variety or scope of the genus," or by the establishment of "a reasonable structure-function correlation." Such correlations may be established "by the inventor as described in the specification," or they may be "known in the art at the time of the filing date." See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014) (Holding that claims to all human antibodies that bind IL-12 with a particular binding affinity rate constant (i.e., koff) were not adequately supported by a specification describing only a single type of human antibody having the claimed features because the disclosed antibody was not representative of other types of antibodies in the claimed genus, as demonstrated by the fact that other disclosed antibodies had different types of heavy and light chains, and shared only a 50% sequence similarity in their variable regions with the disclosed antibodies.).
Claims 15 and 19 encompass bispecific antibodies with broad genera of first antigen binding sites for treating or preventing a CD33-mediated disease or condition (i.e., bispecific T-cell engagers directed to CD33, see ¶[00109]). The USPTO has released a Memo on the Clarification of Written Description Guidance for Claims Drawn to Antibodies and Status of 2008 Training Materials, 02/22/2018.
See https://www.uspto.gov/sites/default/files/documents/amgen_22feb2018.pdf.
The Memo clarifies the applicability of USPTO guidance regarding the written description requirement of 35 U.S.C. § 112(a) concerning the written description requirement for claims drawn to antibodies, including the following:
“In view of the Amgen decision, adequate written description of a newly characterized antigen alone should not be considered adequate written description of a claimed antibody to that newly characterized antigen, even when preparation of such an antibody is routine and conventional”.
In contrast to applicant’s reliance of describing the epitope of “antigen on a cancer cell” (claim 15) and “CD33” (claim 19) in providing a fully characterized antigen/specific epitope as well as claiming structural elements of the antigen, and therapeutic attributes (i.e., for treating or preventing a CD33-mediated disease or condition), there is insufficient written description of the required kind of structure-identifying information about the corresponding makeup of the claimed bispecific antibodies with large genera of first binding sties to demonstrate possession. Also, see Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017).
There is no evidence that knowledge of the chemical structure of an antigen gives the required kind of structure identifying information about the corresponding antibodies Applicants attempt to describe the invention by describing something that is not the invention: viz., the antigens to which the antibodies may bind. There nothing in the disclosure that describes the antibodies as required by the test set forth in Ariad.
However, the bispecific antibodies with broad genera of first binding sites are required to practice the invention. The specification fails to provide any specific structural or physical information so as to define a genus of bispecific antibodies having the desired therapeutic properties. Applicant is merely relying on the identification of either “an antigen on a cancer cell” (claim 15) or “CD33” (claim 19), as the antigen and the well-known structure of antibodies in general. However, the claims do not recite a general antibody, but an antibody having a specific desired activity. The Federal Circuit provided clarification of the law of written description as it applies to antibodies. Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017).
The claims are directed to a genus of bispecific antibodies with broad genera of first binding sites with no structure and the functions of “binding to an antigen on a cancer cell” (claim 15) or “binds to CD33” (claim 19). However, Federal Circuit clarification of the law of written description as it applies to antibodies. The U.S. Court of Appeals for the Federal Circuit (Federal Circuit) decided Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017), which concerned adequate written description for claims drawn to antibodies. The Federal Circuit explained in Amgen that when an antibody is claimed, 35 U.S.C. § 112(a) requires adequate written description of the antibody itself. Amgen, 872 F.3d at 1378-79. The Amgen court expressly stated that the so-called "newly characterized antigen" test, which had been based on an example in USPTO-issued training materials and was noted in dicta in several earlier Federal Circuit decisions, should not be used in determining whether there is adequate written description under 35 U.S.C. § 112(a) for a claim drawn to an antibody. Citing its decision in Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., the court also stressed that the "newly characterized antigen" test could not stand because it contradicted the quid pro quo of the patent system whereby one must describe an invention in order to obtain a patent. Amgen, 872 F.3d at 1378-79, quoting Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1345 (Fed. Cir. 2010). In view of the Amgen decision, adequate written description of a newly characterized antigen alone should not be considered adequate written description of a claimed antibody to that newly characterized antigen, even when preparation of such an antibody is routine and conventional.
Moreover, there is insufficient written description of the required kind of structure-identifying information about the corresponding makeup of the claimed bispecific antibodies with a first binding site with no recited structure and the functions of “binding to an antigen on a cancer cell” (claim 15) or “binds to CD33” (claim 19) to demonstrate possession. Also, see Amgen Inc. v. Sanofi, Aventisub LLC, No. 2017-1480 (Fed. Cir. 2017). The Court reiterated that adequate written description must “contain enough information about the actual makeup of the claimed products . . . .” The Court simultaneously suggested that the “newly characterized antigen” test “flouts” section 112 because it “allows patentees to claim antibodies by describing something that is not the invention, i.e., the antigen.” The Court concluded that for written description of an antibody to be adequate when presented with “functional” terminology, there must be an established correlation in the art between structure and function.
Given the claimed broadly class of first binding sites and in the absence of sufficient disclosure of relevant identifying characteristics for the broadly claimed class of bispecific antibodies with a first binding site with no recited structure and the functions of “binding to an antigen on a cancer cell” (claim 15) or “binds to CD33” (claim 19), the patentee must establish “a reasonable structure-function correlation” either within the specification or by reference to the knowledge of one skilled in the art with functional claims. AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc. (Fed. Cir. 2014), MPEP 2163.
The specification at best describes plan for making bispecific antibodies with a first binding site with no recited structure and the functions of “binding to an antigen on a cancer cell” (claim 15) or “binds to CD33” (claim 19) and then identifying those that satisfy claim limitations, but mere “wish or plan” for obtaining claimed invention is not sufficient. Centocor Ortho Biotech Inc. v. Abbott Laboratories, 97 USPQ2d 1870 (Fed. Cir. 2011).
The specification discloses one bispecific antibody with a first binding site with the structure of “binds to an antigen on a cancer cell” or “binds to CD33”, which is BS824 (¶[00109]).
It is unlikely that bispecific antibodies with first binding sites which may contain less than the full complement of CDRs from the heavy and light chain variable regions of the CD33 first binding site of BS824 fused to framework sequences have the required binding function. The specification provides no direction or guidance regarding how to produce first binding sites as broadly defined by the claims. Undue experimentation would be required to produce the invention commensurate with the scope of the claims from the written disclosure alone. Further, the specification does not teach that a functional antibody can be obtained by replacing the CDR regions of an acceptor antibody with the less than all the 6 CDRs sequences of a donor antibody.
With respect to the recitation of bispecific antibodies with a first binding site with no recited structure and the functions of “binding to an antigen on a cancer cell” (claim 15) or “binds to CD33” (claim 19) which does not comprise all 6 CDRs of the antibody, the Examiner directs Applicant's attention to the training material given by Bennett Celsa, Example 2: (Ab genus: modified CDR's) slides 34-40. Example 2 of the Training material ( https://www.aipla.org/docs/default-source/committee-documents/bcp-files/2020/uspto-bcp-antibody-slides-final.pdf?sfvrsn=b377f2cc_0) which requires that the claims explicitly recite the binding antigen in addition to all 6 CDR regions for fulfillment of the written description requirements under § 112, 1. Slide 39 indicates that a claim encompasses antibodies with 6 intact CDRs as well as a subgenus of antibodies that encompass up to 10% variation (fragments and/or analogs) in the 6 CDRs lacks written description. Slide 40 provide the conclusion that, a single antibody species would not be deemed by one of skill in the art to be representative of a claim that defines an antibody that binds antigen X comprising at least 90% homology to the 6 CDR of the VH and VL chains.
Absent any teaching of structure-function relationships, the skilled in the art cannot determine the critical amino acids in the CDR in the recited sequences and also possess the recited functions of “binding to an antigen on a cancer cell” (claim 15) or “binds to CD33” (claim 19). See AbbVie Deutschland GmbH v. Janssen Biotech, Inc. (Fed. Cir. 2014).
The facts of AbbVie parallel the claimed invention and provide significant guidance on the inherent unpredictability of protein engineering and the effect of amino acid substitutions on protein function. Abbvie is similar to the Federal Circuit's discussion in Novozymes A/S et al. v. Dupont Nutrition Biosciences APS et al., 2013 WL 3779376, Case No. 2012-1433, C.A.Fed; in both, the Federal Circuit emphasized the unpredictability in the art associated with changes in a parent enzyme or protein that can be affected at one or more positions in the sequence by amino acid addition, deletion, or substitution with at least nineteen other possibilities, e.g., counting natural amino acid residues. The basis of the unpredictability is rooted in the same principles that make improvements rare, namely that numerous subtle differences between amino acid residues determine protein binding and function. Because the subtle energetic contributions of each of these interactions is extraordinarily difficult to precisely quantify, and because the number of these interactions is so high even for a single protein-protein interface, innumerable small inaccuracies are amplified into unpredictability. This unpredictability is axiomatic in the field of protein engineering.
For example, functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. Ariad, 598 F.3d at 1351 ("[T]he level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology."); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1352 (Fed. Cir. 2011) (noting the technical challenges in developing fully human antibodies of a known human protein). It is true that functionally defined claims can meet the written description requirement if a reasonable structure-function correlation is established, whether by the inventor as described in the specification or known in the art at the time of the filing date. Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956, 964 (Fed. Cir. 2002). However, the record here does not indicate such an established correlation. Instead, AbbVie used a trial and error approach to modify individual amino acids in order to improve the IL-12 binding affinity. Moreover, the '128 and '485 patents of AbbVie do not describe any common structural features of the claimed antibodies. The asserted claims attempt to claim every fully human IL-12 antibody that would achieve a desired result, i.e., high binding affinity and neutralizing activity, and cover an antibody as different as Stelara, whereas the patents do not describe representative examples to support the full scope of the claims.
Regarding claims 37 and 40:
Claim 37 recites “A monoclonal antibody comprising the sequence of SEQ ID NO: 22 or 122”, which recites specific antibody structures without the epitope in which these two structures bind.
However, the current state of the art in epitope structure prediction is limited given the noncontiguous amino acid residues constitute most epitopes, and that the dynamics of binding is often not integrated into the epitope prediction equation, making epitope structure prediction a complex four-dimensional problem (see Van Regenmortel, page 464, abstract in particular; Methods: A Companion to Methods of Enzymology 9:465-472, 1996). Van Regenmortel notes that 90% of antibodies raised against intact proteins do not react with any peptide fragment derived from the parent protein indicating that these antibodies are directed to discontinuous epitopes (see page 466, column 1 in particular). In addition, Van Regenmortel states that the low success rate of antigenic prediction is due to the fact that predictions concern only continuous epitopes and it is unrealistic to reduce the complexity of epitopes that always possess conformational features to one-dimensional, liner peptide models (see page 467, column 2 in particular). Detailed information regarding the specific epitopes recognized by the anti-α2 antibodies. A skilled artisan would require guidance, such as information regarding the specific epitope recognition of the antibodies successfully used in the instant invention in order to antibodies other than the specific clones in a manner reasonably commensurate with the scope of the claims.
Dependent claim 40 does not resolve this issue and is therefore also rejected under 35 U.S.C. 112(a) WD.
Possession is not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895. Sufficient description to show possession of such a genus may be achieved by means of a recitation of a representative number of anti-TMPRSS6 antibodies or antigen binding fragments thereof falling within the scope of the genus or of a recitation of structural features common to members of the genus, which features constitute a substantial portion of the genus. See Eli Lilly, 119F.3d at 1568, 43 USPQ2d at 1406.
Claims 15, 19, 37, and 40 do not meet the requirements of 35 U.S.C. 112(a) for written description.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the 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.). Consequently, Applicant was not in possession of the instant claimed invention. See University of California v. Eli Lilly and Co. 43 USPQ2d 1398.
Applicant is invited to point to clear support or specific examples of the claimed invention in the specification as-filed.
Amending claim 37 to recite the epitope in which the antibody structures bind (i.e., OX40) would resolve the issues with this claim and dependent claim 40. Support for this can be found in the instant specification in Table 2.
Claims 34 and 35 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: methods of antagonizing CD33 and agonizing OX40 in a subject having cancer comprising administration of a bispecific antibody of claim 22; and methods of antagonizing EGFR and agonizing OX40 in a subject having cancer comprising administration of a bispecific antibody of claim 28, does not reasonably provide enablement for a broad genus of methods of “antagonizing the cancer antigen and agonizing the costimulatory molecule” or “antagonizing the pathogen-infected cell and agonizing a costimulatory molecule” comprising administration of the bispecific antibody of claim 15. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized In re Wands (858 F2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)). The factors most relevant to this rejection are the scope of the claim, the amount of direction or guidance provided, the lack of sufficient working examples, the unpredictability in the art and the amount of experimentation required to enable one of skill in the art to practice the claimed invention.
Breadth of claims and nature of invention:
Claim 34 encompasses a broad method of agonizing any cancer antigen and any costimulatory molecule in a subject having cancer comprising administration of a bispecific antibody comprising an anti-OX40 binding site and a binding site with no structure and the function of “binding to an antigen on a cancer cell”.
Claim 35 encompasses a broad method of agonizing any cancer antigen and any costimulatory molecule in a subject having cancer comprising administration of a bispecific antibody comprising an anti-OX40 binding site and a binding site with no structure and the function of “binding to an antigen on a cancer cell”.
The specification discloses different bispecific antibodies that can function as T-cell engagers for the treatment of cancer (Examples 1-6).
Amount of direction and existence of working examples:
The specification discloses one example of bispecific antibody BS824 (Example 3), which binds to OX40 and CD33 and comprises a HuM195 anti-CD33 antibody binding arm and a OHX14 anti-OX40 antibody binding arm (Figure 1 and ¶[00109]-[00113]). HuM195 comprises the HCDR1-3 of SEQ ID NO: 94-96 respectively and the LCDR1-3 of SEQ ID NO: 97-99 respectively (Table 1), and OHX14 comprises the HCDR1-3 of SEQ ID NO: 13-15 respectively and the LCDR1-3 of SEQ ID NO: 17-19 respectively (Table 1), which is the bispecific antibody encompassed by claim 22. BS824 was found to successfully function as a T-cell engager for cells expressing CD33 (Figure 3 and Example 4).
The specification additionally discloses an anti-EGFR antibody Ch225 that can successfully function in the bispecific engager format (Example 4 and 5), which comprises the HCDR1-3 of SEQ ID NO: 100-102 respectively and the LCDR1-3 of SEQ ID NO: 103-105 respectively (Table 1).
Level of predictability, state of prior art, and quantity of experimentation needed:
The instant specification discloses a method of antagonizing CD33 and agonizing OX40 with the BS824 bispecific antibody, which is the antibody structure encompassed by instant claim 22. The instant specification additionally discloses sufficient guidance to enable one with ordinary skill in the art to make and use a method of antagonizing EGFR and agonizing OX40 with a bispecific antibody comprising the OHX14 anti-OX40 antigen binding arm and the Ch225 anti-EGFR binding arm, which is the antibody structure encompassed by instant claim 26.
However, neither the prior art nor the instant specification provide sufficient guidance to allow one with ordinary skill in the art to make and use a method of antagonizing any cancer antigen (claim 34) or any pathogen-infected cell (claim 35) and agonizing any costimulatory molecule with the antibody of instant claim 15, which has a defined anti-OX40 antigen binding arm and an undefined first antigen binding arm.
Undue experimentation is required by one of ordinary skill in the art to use a method of antagonizing any cancer antigen (claim 34) or any pathogen-infected cell (claim 35) and agonizing any costimulatory molecule with the antibody of instant claim 15. For example, undue experimentation would be required by one of ordinary skill in the art to determine which other costimulatory molecules would be bound by the recited anti-OX40 antigen binding arm in instant claim 15, and undue experimentation would be required by one of ordinary skill in the art to determine which antibody structures would give rise to the functions of “antagonizing the cancer antigen” or “antagonizing the pathogen-infected cell”, or how to distinguish between structures with these functions from those without to lead to the broadly claimed methods.
The specification does not reasonably provide enablement to make and use the invention of instant claims 34 and 35. The specification does provide enablement to make and use the invention discussed supra.
Reasonable correlation must exist between the scope of the claims and scope of the enablement set forth. In view on the quantity of experimentation necessary the limited working examples, the nature of the invention, the state of the prior art, the unpredictability of the art and the breadth of the claims, it would take undue trials and errors to practice the claimed invention.
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.
Claim 30 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 30 currently recites: “The bispecific antibody of claim 28, wherein the first paired heavy chain variable region comprises residues 100-138 of SEQ ID NO: 29…”. Residues 100-138 of SEQ ID NO: 29 do not contain all of the CDRs of SEQ ID NO: 100-102. It is currently unclear how the heavy chain variable region recited in claim 30 comprises the HCDR1-3 sequences recited in instant claim 28. Appropriate correction is required.
Conclusion
A monoclonal antibody specifically binding to OX40 comprising the HCDR1-3 of SEQ ID NO: 13-15 respectively and the LCDR1-3 of SEQ ID NO: 17-19 respectively is neither taught nor suggested by the prior art.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
U.S. Patent No. 11,332,532, which the instant application is a divisional application from, teaches this anti-OX40 antibody structure, however a) this patent is not prior art; and b) the patent does not claim the anti-OX40 antibody and is therefore does not claim overlapping subject matter for the purposes of double patenting.
Claims 31, 32, 36, 38, and 39 are allowed.
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/ALEC JON PETERS/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641