DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 12/30/2025 has been entered.
Applicant’s amendment, filed 12/30/2025, has been entered.
Claims 1-15, 19, 48, 51-69, 94 have been canceled.
Claims 96-98 have been added.
Claims 16-18, 20-47, 49-50, 70-93, 95-98 are pending.
Newly submitted claim 96 is directed to an invention that is independent or distinct from the invention originally claimed for the following reasons:
The antibody that binds DDP3 and the antigen comprising a DDP3 peptide are directed to related products. The related inventions are distinct if: (1) the inventions as claimed are either not capable of use together or can have a materially different design, mode of operation, function, or effect; (2) the inventions do not overlap in scope, i.e., are mutually exclusive; and (3) the inventions as claimed are not obvious variants. See MPEP § 806.05(j). In the instant case, the inventions as claimed are products that are patentably distinct with respect to their structures, physicochemical properties and/or mode of action are different, and they do not share a common structure that is disclosed to be essential for common utility. Furthermore, they require non-coextensive searches in the scientific literature. Moreover, the inventions as claimed do not encompass overlapping subject matter and there is nothing of record to show them to be obvious variants. Therefore, each product is patentably distinct, and searching of these Inventions would impose an undue burden.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claim 96 has been withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Claims 17, 18, 21-25 and 96 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions/species, there being no allowable generic or linking claim.
Claims 16, 20, 26-47, 49-50, 70-93, 95, 97-98 are currently under examination as they read on a DPP3 monoclonal antibody that binds to a DPP3 peptide of SEQ ID NO: 2.
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 16, 20, 26-27, 29-38, 41, 43-47, 49-50, 70-73, 75-80, 82-95, 98 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are directed to a DPP3 binder directed to and binding to a reference epitope. In the present claim, the DPP3 binder is define by the epitope that it recognizes and binding specificity for DPP3. The present claims further define the DPP3 binder of having the function of being effective against various diseases. The breadth of the present claims encompasses a genus of DPP3 binders defined by the binding specificity and function of binding constant and being effective in the treatment of various recited diseases. In claims that recite the heavy chain and light chain CDR sequences, given the “and/or” language, the claims further encompass a subgenus of DPP3 binders that have any one of the reference heavy chain CDRs and any one of the reference light chain CDRs. The present claims do NOT satisfy the written description requirement for the claimed genus for the following reasons:
The written description requirement for a claimed genus may be satisfied through description of 1) a representative number of species OR 2) disclosure of relevant identifying characteristics, i.e., functional characteristics coupled with a known or disclosed correlation between function and structure.
Representative Species
With regard to representative number of species, the instant specification disclosed a single species of the DPP3 binder, i.e., AK1967 (pages 73-76). However, the single disclosed species is not sufficient to represent the entire genus.
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. 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 size of the claimed antibody genus comprises substantial variations as one of skill in the art is well aware of the high level of polymorphism and complex nature of immunoglobulins. Schroeder et al. taught that through somatic variation, combinatorial rearrangement of individual gene segments and combinatorial association between different L and H chains, the repertoire of antibody diversity can have greater than 1016 different immunoglobulins (J Allergy Clin Immunol 2010, 125:S41-S52).
Moreover, it is well-known in the art that antibodies have a large repertoire of distinct structures and that a huge variety of antibodies can be made to bind to a single epitope. For example, Lloyd et al. taught that over 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 (Protein Engineering, Design & Selection 2009, 22:159-168; see, e.g., Discussion).
Therefore, one species is not representative of the claimed genus encompassing the substantial variation due to the high level of polymorphism of antibodies as exemplified by the above references.
Structure-function correlation
While the term “antibody” does impart some structure, the structure that is common to antibodies is generally unrelated to antigen-binding function because antibody CDRs are necessary for binding and they are highly diverse in structure and their sequence does not correlate to binding in a predictable fashion.
It is well established in the art that the formation of an intact antigen-binding site in an antibody usually requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs (or hypervariable regions), which provide the majority of the contact residues for the binding of the antibody to its target epitope. The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites. Even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function as evidenced by Rudikoff et al. (Proc Natl Acad Sci USA 1982 Vol 79 page 1979). Rudikoff et al. teach that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function. MacCallum et al. (J. Mol. Biol. 1996 262, 732-745), analyzed many different antibodies for interactions with antigen and state that although CDR3 of the heavy and light chain dominate, a number of residues outside the standard CDR definitions make antigen contacts (see page 733, right col) and non-contacting residues within the CDRs coincide with residues as important in defining canonical backbone conformations (see page 735, left col.). Pascalis et al. (The Journal of Immunology (2002) 169, 3076-3084) demonstrate that grafting of the CDRs into a human framework was performed by grafting CDR residues and maintaining framework residues that were deemed essential for preserving the structural integrity of the antigen binding site (see page 3079, right col.). Although abbreviated CDR residues were used in the constructs, some residues in all 6 CDRs were used for the constructs (see page 3080, left col.). The fact that not just one CDR is essential for antigen binding or maintaining the conformation of the antigen binding site, is underscored by Casset et al. (BBRC 2003, 307:198-205), which constructed a peptide mimetic of an anti-CD4 monoclonal antibody binding site by rational design and the peptide was designed with 27 residues formed by residues from 5 CDRs (see entire document). Casset et al. also states that although CDR H3 is at the center of most if not all antigen interactions, clearly other CDRs play an important role in the recognition process (page 199, left col.) and this is demonstrated in this work by using all CDRs except L2 and additionally using a framework residue located just before the H3 (see page 202, left col.). Vajdos et al. (J. Mol. Biol. (2002) 320, 415-428), additionally state that antigen binding is primarily mediated by the CDRs more highly conserved framework segments which connect the CDRs are mainly involved in supporting the CDR loop conformations and in some cases framework residues also contact antigen (page 416, left col.). Chen et al. (J. Mol. Bio. (1999) 293, 865-881) describe high affinity variant antibodies binding to VEGF wherein the results show that the antigen binding site is almost entirely composed of residues from heavy chain CDRs, CDR-H1, H2, H3 (page 866). Wu et al. (J. Mol. Biol. (1999) 294, 151-162) state that it is difficult to predict which framework residues serve a critical role in maintaining affinity and specificity due in part to the large conformational change in antibodies that accompany antigen binding (page 152 left col.) but certain residues have been identified as important for maintaining conformation. Padlan et al. (PNAS 1989, 86:5938-5942) described the crystal structure of an antibody-lysozyme complex where all 6 CDRs contribute at least one residue to binding and one residue in the framework is also in contact with antigen. In addition, Lamminmaki et al. (JBC 2001, 276:36687-36694) describe the crystal structure of an anti-estradiol antibody in complex with estradiol where, although CDR3 of VH plays a prominent roll, all CDRs in the light chain make direct contact with antigen (even CDR2 of VL, which is rarely directly involved in hapten binding). Recently, studies have shown that changing in CDRs even alter Fc binding to the Fc receptor and pharmacokinetics (Piche-Nicholas et al. MABS 2018, 10:81-94).
Given the highly diverse nature of antibodies, particularly in the CDRs, by claiming a subgenus of DPP3 binders defined by one of CDRs of the heavy and light chain, one of skill in the art cannot envision the structure of an antibody by knowing its binding characteristics. Therefore, the claims do not satisfy the written description requirement as the structure-function correlation of the claimed genus not sufficiently described.
Given the well-known high level of polymorphism of immunoglobulins / antibodies, the skilled artisan would not have been in possession of the vast repertoire of antibodies and the unlimited number of antibodies encompassed by the claimed invention; one of skill in the art would conclude that applicant was not in possession of the structural attributes of a representative number of species possessed by the members of the genera of DPP3 binders broadly encompassed by the claimed invention. One of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genera.
Response to Applicant’s Argument
Applicant argues that claim 16 recites relevant identifying characteristics and thus satisfies the written description requirement. In response, it is noted that given the highly diverse nature of antibodies, particularly in the CDRs, as discussed in the rejection of record above, by claiming a subgenus of DPP3 binders defined by one of CDRs of the heavy and light chain, one of skill in the art cannot envision the structure of an antibody by knowing its binding characteristics. Therefore, the claims do not satisfy the written description requirement as the structure-function correlation of the claimed genus not sufficiently described.
With respect to newly added claims that recite product-by-process limitations, it is noted that recited product-by-process limitation does not hold patentable weight and does not provide structure sufficient to describe the entire genus encompassed by the claims for reasons explained above.
Therefore, the rejection is maintained as it applies to amended/newly added claims.
Claim Rejections - 35 USC § 103
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.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 16, 20, 43-47, 49-50, 70-71, 83-93, 95 are rejected under 35 U.S.C. 103 as being unpatentable over Lu et al. (Cancer Res; 77(11) June 1, 2017) in view of Campbell (Monoclonal Antibody Technology, 1984, Chapter 1, pages 1-32).
The present claims are directed to a monoclonal antibody that binds a DPP3 peptide comprising the amino acid sequence CETVINPETGEQIQSWYRSGE (SEQ ID NO: 2).
Lu et al. taught that DPP3 containing an “ETGE” motif like NRF1 itself and can bind to KEAP1. Under oxidative stress, this DPP3-KEAP1 interaction increases, reducing the amount of KEAP1 available to bind NRF2 (see, e.g., Introduction). Upon reading the teachings of Lu, one of ordinary skill in the art would have been motivated to make a monoclonal antibody using an antigenic DPP3 peptide containing the ETGE motif because this was a well-known region of DPP3 before the effective filing date of the claimed invention as taught by Lu et al. Furthermore, one of ordinary skill would have been reasonably expected to raise antibodies against a peptide containing ETGE motif because it is customary for any group working on a macromolecule to make monoclonal antibodies to it, sometimes even without a clear objective for their application (see Campbell, page 29, last paragraph).
Moreover, it is noted that the present claims recite product-by-process limitations wherein the antibody is generated by a process comprising injecting an animal with a DPP3 peptide or using recombinant technology. However such process does not distinguish from the peptide taught in the art. “[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).
Furthermore, with regards to affinity constant and inhibition activity, it is noted that given it would have been obvious to make a monoclonal antibody against ETGE motif-containing peptide, the resultant antibody would have these characteristics.
Therefore, the invention, as a whole, was prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention as evidenced by the references, especially in the absence of evidence to the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 16, 20, 26-47, 49-50, 70-93, 95, 97-98 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 11,530,276. Although the claims at issue are not identical, they are not patentably distinct from each other because the patent claims disclosed the same or nearly the same DPP3 binder as the present claims. Therefore, the claims anticipate each other.
Applicant argues that the patent claims are distinct from the present claims. In response, it is noted that the patent claims are directed to a DPP3 binder that reads on an antibody comprising the same CDRs (SEQ ID NOs: 7-9 and 10-KVS-11); same VH and VL (SEQ ID NO: 5, 6) and same heavy and light chains (SEQ ID NO: 12,13). Therefore, the two set of the claims are directed to overlapping subject matter. The rejection is therefore maintained as it applies to amended/newly added claims. Applicant’s request to hold the rejection in abeyance has been noted.
Conclusion
No claim is allowed.
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/SHARON X WEN/Primary Examiner, Art Unit 1641