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 .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Status of Claims
Claims 1-8 and 10-12 are pending and under examination. Claims 9 and 13-33 are canceled.
Maintain Rejections
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 1-8 and 10-12 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.
Scope of the invention
The claims are drawn to an antigen binding protein comprising a first binding component comprising a first human light chain variable hVk domain that binds to a first epitope wherein the hVk domain is cognate with the ULC variable domain and binds the first epitope independently of the ULC variable domain.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of an application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient.” MPEP § 2163. While all of the factors have been considered, a sufficient amount for a prima facie case are discussed below.
Further, to provide evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include: a) the scope of the invention; b) actual reduction to practice; c) disclosure of drawings or structural chemical formulas; d) relevant identifying characteristics including complete structure, partial structure, physical and/or chemical properties, and structure/function correlation; e) method of making the claimed compounds; f) level of skill and knowledge in the art; and g) predictability in the art.
Recently, the U.S. court decided Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017), which concerned adequate written description for claims drawn to antibodies. Amgen v. Sanofi describes how when an antibody is claimed, 35 U.S.C. § 112(a) requires adequate written description of the antibody itself; not just a description of the sequence to which the antibody binds. Amgen, 872 F.3d at 1378-79.
Office guidance has been updated to reflect that adequate written description of a newly characterized antigen protein 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.
“When a patent claims a genus using functional language to define a desired result, the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus" (Capon v. Eshhar, 418 F.3d 1349 (Fed. Cir. 2005)) (emphasis added).
“[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).
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” (AbbVie, 759 F.3d at 1298, reiterating Enzo Biochem, Inc., 323 F.3d at 964)(emphasis added).
In the present case, however, there is insufficient evidence of such an established structure-function correlation of the antigen binding protein having the function of specifically binding to a particular first epitope and the hVk domain is cognate with the ULC variable domain binds the first epitope independently of the ULC variable domain.
Disclosure of drawings or structural chemical formulas/ Actual Reduction to Practice
The specification discloses two (2) sequences (SEQ ID NOs: 1 and 2) for that have been rearranged to produce a specific binding for specific epitopes. Noted that these claims are drawn to generic product claims that are providing functions.
Relevant identifying characteristics including complete structure, partial structure, physical and/or chemical properties, and structure/function correlation
Applicant only discloses two (2) gene sequences that have been rearranged for specific targets, the specification does not disclose any other gene sequences that are responsible for the desired function to bind specifically to a first epitope. The specification fails to disclose, for example, what structural features in the two (2) VL/JL gene sequences are conferring the desired functional property for specific target in Variable Regions and such features are universal to a wide range of sequences. In other words, there is no disclosure of all human sequences when rearranged VL/JL gene sequences would produce the correlated function, as claimed. The disclosure of a specific subset of defined sequences, is not sufficient to reflect the variation within the genus, as claimed.
A skilled artisan cannot, as one can do with a fully described genus, visualize or recognize the identity of the members of the genus that would exhibit this functional property. The structural features common to the members of the genus are unknown.
A limited number of disclosed species would not put one skilled in the art in possession of any other antibodies or fragment domains having the claimed functional properties.
As evidence, see Lloyd et al. ("Modelling the human immune response: performance of a 10e11 human antibody repertoire against a broad panel of therapeutically relevant antigens", Protein Engineering, Design and Selection, Volume 22, Issue 3, 1 March 2009, Pages 159–168, of record 892 dated 12/03/2024), which shows how a repertoire of 1x1011 human antibody variable regions can generate large numbers of unique, biologically active scFvs against a variety of polypeptide targets (see e.g., at page 161-62 bridging paragraph, in Table 1 and Figs. 1-2).
Moreover, Macdonald et al. (US2013/0212719A1, published 08/15/2013, IDS submitted 12/03/2024, cite no. A156) teach that engineering of human immunoglobulin sequences in the genome of a mouse, even at precise locations, e.g., at the endogenous mouse immunoglobulin loci, may presents certain challenges due to divergent evolution of the immunoglobulin loci between mouse and man. For example, intergenic sequences interspersed within the immunoglobulin loci are not identical between mice and humans and, in some circumstances, may not be functionally equivalent and deleterious effects the inability to propagate modified strains, loss of function of essential genes, and inability to express polypeptides, etc., and such deleterious effects may be directly or indirectly related to the modification engineered into the genome of the mouse (at para. [0396]).
As further illustration of the unpredictability in the art, Brown et al. (“Tolerance of single, but not multiple, amino acid replacements in antibody VH CDR 2: a means of minimizing B cell wastage from somatic hypermutation?”, J Immunol. 1996 May;156(9):3285-91, of record dated 12/03/2024), describes how a one amino acid change in the VHCDR2 of a particular antibody was tolerated whereas, the antibody lost binding upon introduction of two amino changes in the same region (at 3290 and Tables 1 and 2).
In view of the above, one cannot visualize or recognize the identities of the members of the genus based from two (2) sequences to exhibit the claimed functional properties of the protein. Although Applicants disclose reduction to practice to two (2) rearranged gene sequences, given the unpredictability of engineering human immunoglobulin sequences in the genome of a mouse and preserving binding abilities, one cannot envision the structures of those produced proteins falling within the claimed genus.
A claimed invention may not be adequately described where an invention is described solely in terms of a method of its making coupled with its function and there is no described or art recognized correlation or relationship between the structure of the invention and its function. See MPEP 2163 II (3), which states that a biomolecule sequence described only by a functional characteristic, without any known or disclosed correlation between that function and the structure of the sequence, normally is not a sufficient identifying characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.
As discussed in the recent case of Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017), see page 17:
An adequate written description must contain enough information about the actual makeup of the claimed products—“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,” which may be present in “functional” terminology “when the art has established a correlation between structure and function.” Ariad, 598 F.3d at 1350. But both in this case and in our previous cases, it has been, at the least, hotly disputed that knowledge of the chemical structure of an antigen gives the required kind of structure-identifying information about the corresponding antibodies. See, e.g., J.A. 1241 (549:5–16) (Appellants’ expert Dr. Eck testifying that knowing “that an antibody binds to a particular amino acid on PCSK9 . . . does not tell you anything at all about the structure of the antibody”); J.A. 1314 (836:9–11) (Appellees’ expert Dr. Petsko being informed of Dr. Eck’s testimony and responding that “[m]y opinion is that [he’s] right”); Centocor, 636 F.3d at 1352 (analogizing the antibody- antigen relationship as searching for a key “on a ring with a million keys on it”) (internal citations and quotation marks omitted).
Amgen Inc. v. Sanofi further notes, pointing to Ariad Pharms., Inc. v. Eli Lilly & Co., 94 USPQ2d 1161 (Fed Cir. 2010):
To show invention, a patentee must convey in its disclosure that it “had possession of the claimed subject matter as of the filing date.” Id. at 1350. Demonstrating possession “requires a precise definition” of the invention. Id. To provide this “precise definition” for a claim to a genus, a patentee must disclose “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.
Amgen at pages 7-8.
In this case, the disclosure of the limited species is insufficient to represent the claimed genus of antigen-binding proteins. As above, a possession of two (2) species reading on the claimed genus does not put one in possession of all rearranged VL/JL gene sequences to produce the protein. As taught in the art, the common structural features that give rise to the desired functional properties are unknown.
Recent court cases have indicated that recitation of an antibody which has specific functional properties in the absence of knowledge of the antibody sequences that give rise to said functional properties do not satisfy the requirements for written description. See AbbVie Deutschland GmbH v. Janssen Biotech. Inc. as well as Amgen v. Sanofi, as discussed above. Indeed, in Amgen the court indicates that that it is improper to allow patentees to claim antibodies by describing something that is not the invention, i.e. the antigen, as knowledge of the chemical structure of an antigen does not give the required kind of structure-identifying information about the corresponding antibodies, with the antibody-antigen relationship be analogized as a search for a key on a ring with a million keys on it.
The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”).
Level of skill and knowledge in the art/predictability in the art
The level of skill in the art is high. Macdonald discloses that engineering of human immunoglobulin sequences in the genome of a mouse, even at precise locations, e.g., at the endogenous mouse immunoglobulin loci, may presents certain challenges due to divergent evolution of the immunoglobulin loci between mouse and man. For example, intergenic sequences interspersed within the immunoglobulin loci are not identical between mice and humans and, in some circumstances, may not be functionally equivalent and deleterious effects the inability to propagate modified strains, loss of function of essential genes, and inability to express polypeptides, etc., and such deleterious effects may be directly or indirectly related to the modification engineered into the genome of the mouse (at para. [0396]). Thus, there is substantial variability within the genus given the diversity in structure of the proteins and the lack of correlation between structure and function.
In summary, the specification fails to provide adequate written description for the claimed genus, as the proteins are either described only in terms of desired functional properties or not enough common structures or other relevant identifying characteristics to define binding abilities. Importantly, the specification merely discloses two (2) sequences generating to engineer human Ig sequences in the genome of a mouse for binding abilities. Therefore, the specification does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the claimed invention.
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 1-8 and 10-12 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites the phrase “universal” is vague and unclear to the person of ordinary skill in the art to determine which are the sequences that are considered universal to produce universal domains. As stated above, the claims do not have structures of the Vk and Jk gene segments to determine whether they are universal sequences. In other words, what is the structural distinction between a universal human Ig and the unarranged human Ig? Also, how is the rearrangement considered to retain a “universal” structure? Additionally, the phrase “a replacement of all functional light chain variable k gene segments” is unclear to what is being replaced when there is no structural feature presented in the claim, a person of ordinary skill in the art would not be able to determine what is being replaced/deleted from the locus with the human Ig. Claims 2-8 and 10-12 are rejected as being dependent from claim 1.
Additionally, claim 2 recites a second binding component comprising a human Ig variable domain is unclear of whether the second binding component is the ULC variable domain or a new domain. As stated above, the term universal is unclear and the ULC variable domain does contain human Ig. Because ULC domain is not a requirement element in product of claim 1, it is unclear whether the ULC domain is the second binding component as it reads on all the structural limitations of the second binding component.
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.
Claims 1-8 and 10-12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Macdonald et al. (US2013/0212719A1, published 08/15/2013, IDS submitted 12/03/2024, cite no. A156).
With respect to claim 1, Macdonald teaches endogenous non-human heavy chain immunoglobulin sequence and the non-human animals rearrange human immunoglobulin light chain gene segments in the context of heavy chain constant regions and express immunoglobulin-like molecules comprising human immunoglobulin light chain variable domains fused to heavy chain constant domains that are cognate with human immunoglobulin light chain variable domains fused to light chain constant domains (at abstract). Macdonald further teaches in Fig. 2 an exemplary targeting strategy for progressive insertion of human Vk and human Jk gene segments into the mouse heavy chain locus resulting in a modified mouse immunoglobulin heavy chain locus comprising human Vk and Jk gene segments operably linked to mouse immunoglobulin heavy chain constant region (also at para. [0362]). Fig. 8 also shows heavy chain locus containing unrearranged human Vk and Jk gene segments operably linked to mouse immunoglobulin heavy chain constant regions (at para. [0368], final product). Macdonald teaches B cells that comprise rearranged immunoglobulin loci (at para. [0126]). Macdonald further teaches the Ig binging protein further comprises a cognate human immunoglobulin light chain variable domain fused with a light chain constant sequence (at para. [0163]). Macdonald teaches human Vk gene segment is Vk 1-39 (at para. [0109]).
Note that the claims are directed to a product of an antigen-binding protein that only requires having a hVk domain. The recitation of “binds a first epitope independently of a cognate universal light chain ULC variable domain” is directed to functional language. Because Macdonald teaches adding human Ig light chain variable kappa (Vk) and human Ig light chain joining kappa (Jk) and rearranged by B cell, the structure of hVk domain would produce the claimed function.
It is also noted that the hVk domain is encoded from human Ig Vk/Jk gene sequence, the recitation of (ii) at an endogenous Ig light chain k locus does not produce the hVk domain.
Additionally, it is noted that MPEP 2113(I) states that product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps.
MPEP 2113(I) also states that "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (citations omitted) (Claim was directed to a novolac color developer. The process of making the developer was allowed. The difference between the inventive process and the prior art was the addition of metal oxide and carboxylic acid as separate ingredients instead of adding the more expensive pre-reacted metal carboxylate. The product-by-process claim was rejected because the end product, in both the prior art and the allowed process, ends up containing metal carboxylate. The fact that the metal carboxylate is not directly added, but is instead produced in-situ does not change the end product.). Furthermore, "[b]ecause validity is determined based on the requirements of patentability, a patent is invalid if a product made by the process recited in a product-by-process claim is anticipated by or obvious from prior art products, even if those prior art products are made by different processes." Amgen Inc. v. F. Hoffmann-La Roche Ltd., 580 F.3d 1340, 1370 n. 14, 92 USPQ2d 1289, 1312, n. 14 (Fed. Cir. 2009). See also Biogen MA Inc. v. EMD Serono, Inc., 976 F.3d 1326, 1334, 2020 USPQ2d 11129 (Fed. Cir. 2020) ("Biogen is certainly correct that the scope of composition and method of treatment claims is generally subject to distinctly different analyses. But where, as here, the novelty of the method of administration rests wholly on the novelty of the composition administered, which in turn rests on the novelty of the source limitation, the Amgen analysis will necessarily result in the same conclusion on anticipation for both forms of claims."); United Therapeutics Corp. v Liquidia Techs., Inc., 74 F.4th 1360, 1373, 2023 USPQ2d 862 (Fed. Cir. 2023) (the court held that product-by-process claims were properly rejected as "anticipated by a disclosure of the same product irrespective of the processes by which they are made."); and Purdue Pharma v. Epic Pharma, 811 F.3d 1345, 117 USPQ2d 1733 (Fed. Cir. 2016). However, in the context of an infringement analysis, a product-by-process claim is only infringed by a product made by the process recited in the claim. Id. at 1370 ("a product in the prior art made by a different process can anticipate a product-by-process claim, but an accused product made by a different process cannot infringe a product-by-process claim").
In this particular case, the final product is a generic structure of a hVk domain (e.g., without a sequence). As stated above, Macdonald teaches the claimed hVk domain and the expressed nucleic acid sequence (see SEQ ID NO: 3 of Macdonald).
With respect to claim 2, Fig. 1 teaches human k light chain locus. Macdonald teaches one or more variable domains fused with the CL region and the variable domains fused with the CH region are human variable domains (at para. [0194]).
With respect to claim 3, Macdonald teaches antigen-binding fragment is scFv (at para. [0312]), which would contain a linker for peptide attachments. Macdonald further teaches the use of spacers are synthesized in adjacent locations with the desired gene segments for construction (at para. [0520]).
With respect to claim 4, Macdonald teaches antigen-binding fragment is Fab (at para. [0312]). Macdonald also teaches Fab fragment comprises rearranged Vk and Jk gene segment ns Fab fragment comprising a first human VL fused with a human light chain constant region, a second human VL fused with a human heavy chain constant region sequence (at paras. [0318]-[0319]. Macdonald teaches antibody-like binding proteins that have two identical polypeptide chains made of the same mouse Ch region fused with a first VL domain, and two identical polypeptide chains made of the same mouse CL region fused with a second human VL domain (at para. [0381]).
With respect to claim 5, Macdonald teaches the human heavy chain constant region comprises a Ch1, a hinge, a Ch2, a Ch3, a Ch4 and a combination thereof (at para. [0332]). Macdonald teaches a nucleic acid sequence encoding a first human light chain immunoglobulin variable sequence (VL1) that is cognate with a second human light chain immunoglobulin variable sequence (VL2), wherein the VL 1 fused with a human Ig light chain region expressed with VL2 fused with a human Ig heavy chain constant region (at para. [0339]). Fig. 1 shows a human universal Ig light chain variable region nucleotide sequence comprising a single human Ig Vk gene segment rearranged with a single human Ig Jk gene segment that encodes a ULC variable domain. Macdonald also teaches an unrearranged human Vk gene segment operably linked to a human J gene segment and a heavy chain constant region sequence , wherein the mouse expresses a VL binding protein that comprises a human Vk domain fused with a heavy chain constant region and a human VL domain fused with a light chain constant domain (at para. [0230]). Macdonald teaches antigen-binding fragment is Fab (at para. [0312]). Macdonald also teaches Fab fragment comprises rearranged Vk and Jk gene segments Fab fragment (tetrameric) comprising a first human VL fused with a human light chain constant region, a second human VL fused with a human heavy chain constant region sequence (at paras. [0318]-[0319]).
With respect to claim 6, Macdonald teaches the mouse comprises a B cell wherein the B cell expresses from a locus on a chromosome of the B cell a binding protein consisting of four polypeptide chains wherein the four polypeptide chains consist of two identical polypeptides (at para. [0184]).
With respect to claims 7-8, Macdonald teaches that mice are provided that express a human immunoglobulin heavy chain variable region (at para. [0047]). Macdonald teaches a replacement of one endogenous Ig heavy chain variable region gene segment (at para. [0098]).
With respect to claim 10, Macdonald teaches human Vk gene segment is Vk 1-39 (at para. [0109]). Macdonald teaches Jk is Jk1 or Jk5 (at para. [0178]). Macdonald teaches the mouse comprises a plurality of human V gene segments, a plurality of J gene segments (at para. [0108]).
With respect to claim 11, Macdonald teaches human Vk gene segment is Vk 1-39 (at para. [0109]). Macdonald teaches Jk is Jk1 or Jk5 (at para. [0178]).
With respect to claim 12, Macdonald teaches a fully human Fab is formed (at para. [0228]).
Response to Arguments
Applicant's arguments filed 07/22/2026 have been fully considered but they are not persuasive.
35 U.S.C. 112(a), written description:
Applicant argues pages 7-13 that (a) there is sufficient evidence of an established structure-function correlation for the claimed antigen-bind protein, as provided in the Application as filed, and in light of the knowledge common in the art at the time of filing, (b) the Application as filed clearly describes and demonstrates the structural features of the claimed hVk domain that confers the function of binding to an epitope independently of a cognate ULC, and (c)because of the established structure-function correlation, a skilled artisan could readily recognize the identity of the members of the genus that would exhibit the functional property encompassed in the claims. In particular, Applicant argues pages 8-9 that a universal light chain (ULC) has an art established function of driving antigen-binding capacity towards a cognate heavy chain variable domain (see McWhirter, US2013/0198879). Applicant also argues pages 10-13 that the filed Application has demonstrated that human Vk domains produced in the presence of a cognate ULC bind to antigen independently of the cognate ULC.
The arguments are not found persuasive for the following reasons. Note that the claims are directed to a product.
Although McWhirter has established the use of universal light chain for heavy chain variable domain, McWhirter only discloses deriving from 2 (two) specific nucleic acid sequences (Vk1-39Jk5, SEQ ID NO: 59; and Vk3-20Jk1, SEQ ID NO: 69)). Importantly, Table 10 shows that even from known sequences antibody titer was only increased to about 61% (42 of 69) heavy chains when paired with the rearranged human Vk1-39Jk5 and about 29% (20 of 69) heavy chains when paired with the rearranged human Vk3-20Jk1 as compared to the cognate light chain of the parental antibody (para. [0337]). McWhirter also teaches that the universal light chain is a light chain derived from a rearranged human light chain variable sequence selected from a human Vk1-39Jk5 or Vk3-20Jk1 (para. [0069]). Table 14-15 show the common light chain antibodies of Vk1-39Jk5 or Vk3-20Jk1.
These passages from McWhirter have established that even though nucleic acid sequences are described, experimentation for polyclonal is required for functional characteristics (i.e., not predictable). Therefore, McWhirter is not enough to provide evidence to establish the claimed hVk domain for the light chain variable expressed from a generic nucleic acid comprising just a rearranged human Ig Vk/Jk gene such that (1) all the species of a generic hVk domain would bind to the same first epitope and (2) all the species of said generic hVk domain would bind an epitope independently of the cognate ULC variable domain.
With respect to the instant Application satisfying written description, the Application has only demonstrated with 2 (two) specific nucleic acid sequences which are the same as McWhirter’s SEQ ID NOs: 59 and 69. As stated above, producing polyclonal antibodies are not predictable. The passages from McWhirter have established that even from known nucleic acid sequences, functional is not predictable (e.g., Table 10). Therefore, a generic nucleic acid sequence comprising a rearranged human Ig Vk/Jk gene sequence is not predictable to produce the function as claimed without specific structures (i.e., sequences).
As evidence, see Lloyd et al. ("Modelling the human immune response: performance of a 10e11 human antibody repertoire against a broad panel of therapeutically relevant antigens", Protein Engineering, Design and Selection, Volume 22, Issue 3, 1 March 2009, Pages 159–168, of record 892 dated 12/03/2024), which shows how a repertoire of 1x1011 human antibody variable regions can generate large numbers of unique, biologically active scFvs against a variety of polypeptide targets (see e.g., at page 161-62 bridging paragraph, in Table 1 and Figs. 1-2). Thus, it is not predictable with a generic nucleic acid sequence as claimed. Note that Lloyd has been reintroduced because the process to the product-by-process has been amended.
35 U.S.C. 112(b):
Applicant argues on pages 13-16 that the terms and description in the claims are consistent with recitations of the term “universal light chain” or ULC disclosed in the Application as filed. Thus, the allegations that the claims do not have structures of the Vk and Jk gene segments to determine whether they are universal sequences are without merit.
The arguments are not found persuasive for the following reasons. The claims are directed to a product claim. Because the hVk domain nor the expressed nucleic acid sequence contains specific structure (e.g., sequence or region of amino acids), it is unclear how the rearrangement would generate the phrase “universal light chain variable region” as stated above.
35 U.S.C. 102(a)(1):
Applicant argues pages 16-19 that Applicant disagrees with the allegations because the structure implied by the process steps of the product-by-process claim is relevant to patentiability and (b) Macdonald does not teach or suggest a “a cognate ULC” variable domain of the hVk domain or a “hVk domain that binds a first epitope independently of cognate ULC variable domain as encompassed by the present claims.
The arguments are not found persuasive. Even though the structure implied by the process steps, in this case, Macdonald teaches the structure of the hVk domain and the expressed nucleic acid sequence as claimed. The final product of the product-by-process claim is evaluated for patentability. Macdonald does teach, for example, SEQ ID NO:3 which would read on the claimed expressed nucleic acid sequence. Meanwhile, Applicant has not pointed out what structure (i.e., amino acids) in the claimed hVk domain and/or the expressed nucleic acid sequence are different from Macdonald’s structures. Thus, Macdonald’s domain or nucleic acid sequence (e.g., SEQ ID NO: 3) would read on the antigen-binding protein comprising a first binding component comprising hVk domain expressed by a generic nucleic acid sequence. Thus, the rejection is maintained.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/N.P.N/Examiner, Art Unit 1678
/SHAFIQUL HAQ/Primary Examiner, Art Unit 1678
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