Patent Application 17633131 - ANTI-HOG TCN1 MONOCLONAL ANTIBODIES AND METHODS

Title: ANTI-HOG TCN1 MONOCLONAL ANTIBODIES AND METHODS OF PRODUCTION AND USE THEREOF

Application Information

Invention Title: ANTI-HOG TCN1 MONOCLONAL ANTIBODIES AND METHODS OF PRODUCTION AND USE THEREOF
Application Number: 17633131
Submission Date: 2025-05-15T00:00:00.000Z
Effective Filing Date: 2022-02-04T00:00:00.000Z
Filing Date: 2022-02-04T00:00:00.000Z
National Class: 424
National Sub-Class: 133100
Examiner Employee Number: 80277
Art Unit: 1674
Tech Center: 1600

Rejection Summary

102 Rejections: 0
103 Rejections: 1

Cited Patents

No patents were cited in this rejection.

Office Action Text

DETAILED ACTION

Status of Application, Amendments and/or Claims
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . Claims 1-27 are pending.

Election/Restrictions
Applicants' election with traverse of Group I, claims 1-9, 13, 14 and 26-27 (in part), as drawn to an antibody that binds to hog transcobalamin (TCN1) in the reply filed on 4/29/25 is acknowledged. The traversal is on the ground(s) that “there is no burden on searching all of the groups as set forth” in the restriction requirement”.
This is not found persuasive because the criteria for restriction in national stage applications filed under 371 do not include search burden, and the basis set forth in the Office action mailed on 2/25/25 did not include search burden. Claims 10-12 and 15-25 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
The election with traverse of “(d) Antibody with heavy and light chain variable regions of SEQ ID NO: 49/54” as the species of anti-hog TCN1 antibody in the reply filed on 4/29/25 is also acknowledged. The traversal is on the grounds that “[t]here is no burden on the examiner in examining the claims”.
This is not found persuasive because the criteria for restriction in national stage applications filed under 371 do not include search burden, and the basis for the election of species requirement set forth in the Office action mailed on 2/25/25 did not include search burden.
Claims 1-9, 13, 14 and 26-27 are under consideration, as they read upon the elected species.

Specification
The disclosure is objected to for the following informalities:
---In each of ¶ 69 (three instances), 72 (two instances), 74, 101, 103 and 111, the term “transcobalamine-1” should be spelled “transcobalamin I”. Compare with each of ¶ 3, 9 and 68, where it is spelled “Transcobalamin 1”, as well as Marcoullis et al, 1977 (cited on the 6/5/23 IDS).
---In each of ¶ 51 on page 15 and on ¶ 98 on page 29, “F(ab’)2” should be F(ab’)2”. Compare with the format of the same term in ¶ 50 on page 15.
---The use of trademarks has been noted. Each should be accompanied by the generic terminology, and 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 trademarks is permissible in patent applications, the proprietary nature should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. The following usage requires correction:
In ¶ 158 on page 44, the trademark “TRIZOL®” is used but without being accompanied by the generic terminology.
Appropriate correction is required.

Claim Objections
Claims 1-9, 13, 14 and 26-27 are objected to for the following informalities:
In claim 1, line 2, and claim 9, line 1, the word “which” should be “that”.
In each of claims 1 and 9, line 2 of each, “Transcobalamine-1” should be spelled “Transcobalamin I”. See above.
In claim 2, lines 4, 7, 10 and 13 (4 instances), and claim 9, line 2, “hog” should be spelled “Hog” as in claim 1, line 2; alternately, “Hog” in claim 1 should be “hog”.
In claim 7, line 3, “F(ab’)2” should be F(ab’)2”. Compare with the format of the same term in ¶ 50 on page 15 of the specification.
Claims 26 and 27 are objected to for encompassing non-elected inventions; specifically, the hybridoma, polynucleotide, vector and recombinant host cell, each of which is derived from a different product (polynucleotide) from that of elected invention (antibody).
The remaining claim(s) are objected to for depending from an objected claim.
Appropriate correction is required.

Claim Rejections - 35 USC § 112(a), written description
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.

Claim 9 is 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.
Per MPEP 2163, 35 U.S.C. 112(a) requires, “separate and distinct from the enablement requirement”, that the “specification shall contain a written description of the invention…” (Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1355 (Fed. Cir. 2010)). In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112(a), it is necessary to understand what Applicants are claiming and what Applicants have possession of.
Claim 9 is an independent claim directed to a product, which is an antibody, or antigen-binding fragment thereof, that can specifically bind to an epitope of the protein transcobalamin (TCN1) from hogs comprising a portion at least one of SEQ ID NO: 2-4 or 20-23. The specification identifies SEQ ID NO: 2-4 as peptides R1-R3, which consist of residues 29-39 (R1), 80-89 (R2) or 200-215 (R3) of the full-length protein, which is given as SEQ ID NO: 1 (417 amino acids in length). Table 4 on page 42 identifies SEQ ID NO: 20-23 as consisting of residues 82-87 (SEQ ID NO: 20), 46-57 (SEQ ID NO: 21), 113-121 (SEQ ID NO: 22) or 121-131 (SEQ ID NO: 23) of SEQ ID NO: 1.
The prior art recognizes that antibodies bind to epitopes of 5-7 amino acids (Benjamini et al, 1991. Immunology: A Short Course, 2nd edition, page 40 only). While the general structure of an antibody was well-known in the prior art, it is the structure of the complementarity-determining regions (CDRs) that determines the specificity of a particular antibody, and said CDR structure is not predictable based on the epitope to which it binds. Thus, even knowing the structure (CDRs) of one antibody does not allow the skilled artisan to predict the structure of other antibodies that bind to the same epitope or to the other epitopes in the same protein. The relevant art, Ferrara et al (2015. mAbs. 7(1): 32-41) teaches that there is substantial variation in the structure of antibodies that bind to a single protein, on the order of hundreds of different sequences; specifically, see page 36: "The number of different HCDR3s selected against the test antigens ranges from 74 to 460 (Table 3), with the actual number of different antibodies likely to be significantly higher when different VL chains and additional VH mutations are taken into account” (pg 36).
Thus, the claims are genus claims because they encompass use of a genus of antibodies having the required functionality, i.e., specifically binding to a portion of SEQ ID NO: 2, 3, 4, 20, 21, 22 or 23. However, a product defined by function is not in and of itself sufficient to describe the product because it is only an indication of what the product does, rather than what it is; i.e., the specific structure of the product. It is only a definition of a useful result rather than a definition of what achieves that result. Per MPEP 2124, "describing a composition by its function alone typically will not suffice to sufficiently describe the composition". Furthermore, in the instant case the specification does not establish a correlation between structure and function; i.e., the structure of one anti-TCN1 antibody does not provide predictability regarding other antibody structures having the same functionality. Furthermore, the decision of the Federal Circuit in Amgen v. Sanofi, 872 F.3d 1367 (Fed. Circ. 2017) held that a claim directed to an antibody requires written description of the antibody itself rather than being satisfied solely by a written description of the antigen to which it binds (the so-called "newly characterized antigen" test). Thus, a description of the target protein (e.g. an epitope of TCN1) is not in and of itself sufficient to provide a written description of the genus of antibodies binding to said target protein.
Written description for a claimed genus may also be satisfied through sufficient description of a relevant number of species. This is dependent on whether one of skill in the art would recognize necessary common attributes or features possessed by the members of the genus. Generally, 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. Also, “[w]hen 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)). “[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).
The specification provides four examples of antibody structures that bind to the specified epitopes. These antibodies are designated 171B 1G5; 171J 3F1; 171J 3A6 and 171J 5H12, and Table 4 of the specification indicates that they respectively bind to residues 82-87 (SEQ ID NO: 20), 46-57 (SEQ ID NO: 21), 113-121 (SEQ ID NO: 22) or 121-131 (SEQ ID NO: 23) of SEQ ID NO: 1. Table 6 on page 45 provides the CDR sequences for each of these antibodies 171B 1G5; 171J 3F1; 171J 3A6 and 171J 5H12, thus describing a single structure that binds to each of these sequences. SEQ ID NO: 20 (residues 82-87) is also a subset of SEQ ID NO: 2 (residues 80-89), and thus the specification also provides a single structure that binds to SEQ ID NO: 2. However, each of the sequences recited in the claims is not a single epitope that produces a single antibody that binds to it. Instead, SEQ ID NO: 2-4 and 20-23 are 11, 10, 16, 6, 12, 9 or 11 amino acids in length, and thus each encompasses multiple potential epitopes, as evidenced by Benjamini et al (1991; cited above), which teaches that epitopes are between 5-7 amino acids in length. Furthermore, the claims encompass antibodies that bind any “portion” of any of SEQ ID NO: 2-4 or 20-23, which includes overlapping epitopes include any fragment of SEQ ID NO: 2-4 or 20-23; e.g., an antibody that binds residues 78-83, which includes a “portion” (two amino acids) of SEQ ID NO: 20. Furthermore, each epitope is capable of generating multiple antibodies having different CDR structures that bind to the same epitope structure.
The limited description of four species is not sufficient to be representative of a genus encompassing hundreds of members. Per MPEP 2163, "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 AbbVie 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.")
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111 (Fed. Cir. 1991), clearly states “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” (pg 1117). The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed” (pg 1116).
Therefore, the claimed method of treatment of ischemic diseases and/or ischemic tissue damage fails to meet the written description provision of 35 U.S.C. §112(a) beyond an antibody comprising a set of six CDRs disclosed in the specification as binding to one of the specified epitopes; i.e., an antibody comprising SEQ ID NO: 8-10 and 14-16 that binds to the epitope consisting of SEQ ID NO: 20. Applicants are reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (pg 1115).

Note on Prior Art Rejection(s)
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 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.

Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.

This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were effectively filed absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned at the time a later invention was effectively filed in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.

Claim 9 is rejected under 35 U.S.C. 103(a) as being unpatentable over Hewitt (1990. Eur J Biochem. 189: 125-130), and further in view of Campbell (1984, Laboratory Techniques in Biochemistry And Molecular Biology, Volume 13, Chapter 1, pages 1-33).
Claim 9 encompasses an antibody that can specifically bind to an epitope of hog transcobalamin (TCN1) comprising a portion of SEQ ID NO: 3 (QDDMNRRDMS), which corresponds to residues 80-89 of the full-length protein.
Hewitt teaches peptide HR2 consisting of amino acids QDDMNR from the hog haptocorrin protein, which is another name for transcobalamin I, which was identified by tryptic digest and isolation (page 126). This peptide comprises a portion of SEQ ID NO: 3; specifically, the first six amino acids. Hewitt further discusses antibodies to porcine haptocorrin (page 129), but does not teach an antibody to the peptide HR2.
Campbell teaches methods for producing monoclonal antibodies, including producing "an antibody of the required immunoglobulin class, specificity and affinity" (pg 4). Campbell further teaches that it is “customary now for any group working on a macromolecule to both clone the genes coding for it and make monoclonal antibodies to it (sometimes without a clear objective for their application)” (pg 29). Campbell further teaches that “As a standard reagent, a monoclonal antibody is undoubtedly superior to polyclonal antiserum” (pg 13).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to take the HR2 peptide fragment of haptocorrin (transcobalamin I) taught by Hewitt and use it to make a monoclonal antibody as taught by Campbell that specifically binds the peptide. The person of ordinary skill in the art would have been motivated to do so in order to produce a monoclonal antibody that specifically binds transcobalamin I, for example for use as a standard reagent as taught by Campbell for monoclonal antibodies. Further, a person of ordinary skill in the art would have had a reasonable expectation of success because Campbell teaches that production of monoclonal antibodies to a known protein is routine in the art. This rationale supports a prima facie conclusion of obviousness in accord with KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (2007). Such an antibody would meet the limitations of claim 9 because it can specifically bind to an epitope comprising a portion of SEQ ID NO: 3.

Note on Patentability
No prior art has been identified that teaches or suggests an antibody that can specifically bind to Hog Transcobalamin I (TCN1) wherein the antibody comprises one of the five specific sets of six CDRs recited in parts (A)-(E) of claim 1; e.g., an antibody comprising a heavy chain variable region CDR1-3 of SEQ ID NO: 8, 9 and 10, and a light chain variable region CDR1-3 of SEQ ID NO: 14-16.

Conclusion
No claims are allowable, but claims 1-8, 13, 14 and 26-27 would be allowable if the informalities objected to above are corrected.

Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZACHARY C HOWARD whose telephone number is (571)272-2877. The examiner can normally be reached on Monday to Friday from 9 AM to 5 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Vanessa Ford, can be reached at telephone number (571) 272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from Patent Center. Status information for published applications may be obtained from Patent Center. Status information for unpublished applications is available through Patent Center for authorized users only. Should you have questions about access to Patent Center, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) Form at https://www.uspto.gov/patents/uspto-automated-interview-request-air-form.

/ZACHARY C HOWARD/Primary Examiner, Art Unit 1674