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
Applicant’s election without traverse of Group I, is acknowledged and has been entered. Applicant has elected the species of antibody comprising SEQ ID NO:2 and 20, which comprise the CDR sequences of SEQ ID Nos:44-46 and 98-100.
Claims 1-3, 5-6, 8-9, 11-12, 15-17, 25-27, 29, 31 and 35-37 are pending. Claims 25-27, 31, 35 and 37 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1-3, 5-6, 8-9, 11-12, 15-17, 29 and 36 are under consideration.
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 6, 12, 16, 7 and 36 are 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 pre-AIA the applicant regards as the invention.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) is considered indefinite, since the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). Note the explanation given by the Board of Patent Appeals and Interferences in Ex parte Wu, 10 USPQ2d 2031, 2033 (Bd. Pat. App. & Inter. 1989), as to where broad language is followed by "such as" and then narrow language. The Board stated that this can render a claim indefinite by raising a question or doubt as to whether the feature introduced by such language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Note also, for example, the decisions of Ex parte Steigewald, 131 USPQ 74 (Bd. App. 1961); Ex parte Hall, 83 USPQ 38 (Bd. App. 1948); and Ex parte Hasche, 86 USPQ 481 (Bd. App. 1949).
In the present instance, these claims recite broad limitations and then the language “optionally” with narrower limitations, so it is unclear how or when the narrow limitation further limits the claim.
Accordingly, due to the ambiguity that results from a broad limitation followed by a narrow limitation used in this claim, the claim fails to delineate the metes and bounds of the subject matter regarded as the invention with the clarity and particularity necessary to satisfy the requirement set forth under 35 U.S.C. § 112, second paragraph, so as to permit the skilled artisan to know or determine infringing subject matter.
It is suggested that any optional limitation be removed from the claims to obviate the rejection.
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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 1-3, 5-6, 8-9, 11-12, 15-17, 29 and 36 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. This is a written description rejection.
“[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). See also MPEP 2163.04.
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 teachings of the specification and the claimed invention:
The nature and scope of the claimed invention at issue is a genus of compositions that comprises an antibody moiety comprising: (a) a heavy chain immunoglobulin variable domain (VH) comprising a VH-CDR1 sequence, a VH-CDR2 sequence, and a VH-CDR3 sequence of the VH sequence of SEQ ID NO: 2, and a light chain immunoglobulin variable domain (VL) comprising a VL-CDR1 sequence, a VL-CDR2 sequence, and a VL-CDR3 sequence of the VL sequence SEQ ID NO: 20 that does not bind any particular antigen (see claim 1) and a genus that comprises an anti-NDC80/MHC composition comprising an antibody moiety that competes with such an antibody moiety (see claim 8).
Such antibody moieties in the first genus are thus not defined by functional feature that correlates with the claimed CDR structure and in the second genus such antibody moieties are defined by the function of competing with such an antibody moieties.
Notably, it is apparent that the first genus need not have the function of binding a NDC80 peptide/HLA-A*02 complex, wherein said NDC80 peptide comprises the amino acid sequence ALNEQIARL (SEQ ID NO: 1) because the claims do not require said function and the specification states that the “present disclosure identifies and characterizes immunoglobulin-related compositions (e.g., antibodies including human, humanized, or chimeric antibodies, antibody fragments, chimeric antibody-T cell receptors (caTCRs), chimeric antigen receptors (CARs), fusion proteins, and conjugates thereof) that are able to target cytosolic/intracellular proteins (see ¶ 0009)
However, the instant specification discloses generating antibodies that bind a NDC80 peptide/HLA-A*02 complex, wherein said NDC80 peptide comprises the amino acid sequence ALNEQIARL (SEQ ID NO: 1) and that one such antibody comprises an antibody moiety comprising: (a) a heavy chain immunoglobulin variable domain (VH) comprising a VH-CDR1 sequence, a VH-CDR2 sequence, and a VH-CDR3 sequence of the VH sequence of SEQ ID NO: 2, and a light chain immunoglobulin variable domain (VL) comprising a VL-CDR1 sequence, a VL-CDR2 sequence, and a VL-CDR3 sequence of the VL sequence SEQ ID NO: 20.
The instant specification has not disclosed any other cytosolic/intracellular protein antigens such an antibody moiety would bind or representative antibodies that compete with such an antibody moiety for binding to NDC80 peptide/HLA-A*02 complex, wherein said NDC80 peptide comprises the amino acid sequence ALNEQIARL (SEQ ID NO: 1).
State of the Art
It is well established in the art that conventional antibodies have a large repertoire of distinct structures and that a huge variety of antibodies can be made to bind to a single antigen where some antibodies bind different epitopes on the antigen and some bind overlapping or the same epitope which allows them to compete for binding. For example, Lloyd et al (Protein Engineering, Design & Selection, 22:159-168, 2009) teach that hundreds of functional antibody fragments can be isolated from an antibody library that bind to the same antigen wherein these antibodies have distinct heavy and light chain sequences and can bind different epitopes on the antigen (see, e.g., Discussion). Similarly, Edwards et al (J Mol Biol, 14;334(1):103-118, 2003), found that over 1000 antibodies, all different in amino acid sequence, were generated to a single protein with 568 different amino acid sequences identified for the V(H) CDR3 domains of these antibodies (see Abstract).
It is also known in the antibody art that the formation of an intact antigen-binding site in a conventional 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 et al, (Frontiers in Immunology (2018) 8: 1751, pages 1-19), (“The IgG Molecule” (page 3) and Figure 1). 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, pages 3 and 6-7).
Therefore, it is expected that all 6 CDRs of a conventional antibody needs to be grafted into antibody framework regions to retain the requisite specificity and functionality of the parent antibody and that it cannot be known what other antigens any particular moiety will bind other than the one tested. Notably, as antibodies are produced by genetic recombination and affinity maturation via mutations in the hypervariable CDR regions, the CDRs of one antibody with a particular function does not inform the skilled artisan as to other CDRs in antibodies that could be obtained with the same function of binding a NDC80 peptide/HLA-A*02 complex, wherein said NDC80 peptide comprises the amino acid sequence ALNEQIARL (SEQ ID NO: 1) or which other antigens the moiety might bind.
Claim Analysis
The instant claims are described above.
A skilled artisan in the art would recognize that the specificity of an antibody is dependent upon six specific CDR sequences and different modifications of CDR sequences greatly alter antigen binding. The instant specification discloses antibodies with 6 CDRs that a NDC80 peptide/HLA-A*02 complex, wherein said NDC80 peptide comprises the amino acid sequence ALNEQIARL (SEQ ID NO: 1).
However, the claims encompass antibodies without a defined function and antibodies that compete with such an antibody to some extent. As a skilled artisan cannot predict what other antigens might be bound by the antibody and cannot know which antibodies would compete for binding, the instant disclosure would not permit a skilled artisan to envision the genus of antibodies as claimed.
Notably, antibodies often cross-react with other epitopes on other antigens, but without screening for binding to other antigens, one of ordinary skill cannot predict the specific antigens the claimed antibody moiety might bind. Because of the unpredictability of the art, the applicant has not shown they are in possession of the genus of such antibodies.
Then with particular reference to antibodies that compete for binding with claimed antibodies, the disclosed antibody is not representative of the other claimed antibodies. This is because when antibodies are raised to an antigen each monoclonal antibody raised comes from one unique cell with unique CDRs which are responsible for antibody binding, such that the structure of CDRs for one antibody cannot be considered representative of other antibodies with different CDRs that bind the same antigen or even substantially the same epitope. Notably, the epitope structure that one antibody binds on an antigen, do not inform the skilled artisan as to what other antibodies would bind the same or substantially the same structure. Furthermore, in the sequence search of the CDR sequences, 100% identical sequences were identified in antibodies that bind other antigens (see search of the CDR sequences). Therefore, it is apparent that single CDR sequence structure or partial CDR structure does not correlate with the function of binding a NDC80 peptide/HLA-A*02 complex, wherein said NDC80 peptide comprises the amino acid sequence ALNEQIARL (SEQ ID NO: 1).
The disclosure therefore does not show that applicant was in possession of the necessary common attributes or features possessed by the members of the claimed genera. Accordingly, the skilled artisan would not recognize that applicants were in possession of the invention as broadly claimed at the time the application was filed.
It is suggested that the rejection could be obviated by amending the claims to be drawn to an antibody moiety that binds a NDC80 peptide/HLA-A*02 complex, wherein said NDC80 peptide comprises the amino acid sequence ALNEQIARL (SEQ ID NO: 1), wherein the antibody moiety comprises a heavy chain immunoglobulin variable domain (VH) comprising a VH-CDR1 sequence, a VH-CDR2 sequence, and a VH-CDR3 sequence of the VH sequence of SEQ ID NO: 2, and a light chain immunoglobulin variable domain (VL) comprising a VL-CDR1 sequence, a VL-CDR2 sequence, and a VL-CDR3 sequence of the VL sequence SEQ ID NO: 20 and cancelation of claim 8.
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.
Claim 8 is rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Tsuunoda et al (US Patent 9,597,382, IDS) as evidenced by the definition of “polyclonal antibody” attached as Exhibit A and Lippincott-Schwartz (Current Protocols in Cell Biology, 16.0.1-16.0.2, 2002).
Notably, claim 8 encompasses compositions comprising antibodies that bind that compete with a claimed antibody moiety.
Tsuunoda et al discloses polyclonal and monoclonal antibodies that bind to a NDC80 peptide/HLA-A*02 complex, wherein said NDC80 peptide comprises the amino acid sequence ALNEQIARL (SEQ ID NO: 1) (see background, Table 1a and columns 14 and 41-44).
In this case, as evidenced by the attached Exhibit A, polyclonal antibodies bind to multiple epitope sites on an antigen of interest. Accordingly, while Tsuunoda et al did not test their antibodies for the ability to compete with the claimed antibody moiety, since polyclonal antibodies comprise a heterogeneous population of antibodies that bind the multiple immunogenic epitopes of an antigen, the polyclonal antibodies of Tsuunoda et al necessarily compete with the claimed antibody.
Furthermore, as evidenced by Lippincott-Schwartz polyclonal antibodies are a collection of monoclonal antibodies (see 16.0.1), so the antibodies of Tsuunoda et al include monoclonal antibodies that compete with antibodies encompassed by the claims.
In this case, the Office does not have the facilities for examining and comparing Applicant's products with the products of the prior art in order to establish that the products of the prior art possesses the same material, structural, and functional characteristics as Applicant’s products. In the absence of evidence to the contrary, the burden is upon the applicant to prove that the products to which the claims are directed are different than that taught by the prior art. See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA, 1977) and Ex parte Gray, 10 USPQ2d 1922 1923 (PTO Board of Patent Appeals and Interferences, 1988 and 1989). Notably, the Office cannot compare the binding of the antibodies disclosed in Tsuunoda et al to the claimed antibodies for competition.
Therefore, the products of Tsuunoda et al are deemed to anticipate the claimed products 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 can normally be reached Mon-Fri.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Julie Wu can be reached at 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
May 26, 2026
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