DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
2. Applicant’s election without traverse Group I, claims 1-16 in the reply filed on 23 July 2026 is acknowledged. Applicant’s election of the following species, in the reply filed on 23 July 2026 is also acknowledged:
(A) Dsg3 of SEQ ID NO: 6 as the species of autoantigen;
(B) CD8alpha as the species of transmembrane domain; and
(C) CD3zeta as the species of intracellular domains.
Claims 19-20, 34 and 40 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 23 July 2026.
Status of Application, Amendments, and/or Claims
3. The Response filed on 23 July 2026 has been entered in full. Claims 19-20, 34 and 40 have been withdrawn as discussed supra. Therefore, claims 1-16, 19-20, 34 and 40 are pending, and claims 1-16 are the subject of this Office Action. The claims also read on the elected species set forth supra and have been examined to the extent they read on such.
Information Disclosure Statement
4. The information disclosure statement (IDS) submitted on 15 June 2023 has been considered by the Examiner.
Specification
5. The disclosure is objected to because of the following informalities: The Specification at pg. 61 recites “□□□□1.” Applicant is requested to correct any additional errors which they may become aware.
Appropriate correction is required.
Claim Rejections - 35 USC § 112, 1st Paragraph (Written Description)
6. 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.
7. Claims 1-2 and 4-16 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.
8. The claims are drawn quite broadly to an isolated nucleic acid sequence encoding a chimeric autoantibody receptor (CAAR), wherein the isolated nucleic acid sequence comprises a nucleic acid sequence of an autoantigen or fragment thereof, a nucleic acid sequence of a transmembrane domain, a nucleic acid sequence of an intracellular domain of a costimulatory molecule, and a nucleic acid sequence of a signaling domain. The claims also recite wherein the autoantigen is selected from the group consisting of Dsgl, Dsg3, and a fragment thereof. The claims also recite a vector comprising said nucleic acid molecule. Thus, the claims are drawn to an extremely large genus of nucleic acid molecules encoding chimeric autoantibody receptors that are only defined by a very limited partial structure and a desired function. However, the specification does not provide sufficient written description as to the structural features of the claimed genus of chimeric autoantibody receptors that is encompassed by the claims, nor does it describe a representative number of species that have the recited functions.
9. 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. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]." See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004)("[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated."). "A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed." In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004)(Claims directed to PTFE dental floss with a friction-enhancing coating were not supported by a disclosure of a microcrystalline wax coating where there was no evidence in the disclosure or anywhere else in the record showing applicant conveyed that any other coating was suitable for a PTFE dental floss.).
10. In the instant case, the claims are drawn quite broadly to a nucleic acid sequence encoding a chimeric autoantibody receptor (CAAR) which generically comprises “a nucleic acid sequence encoding an autoantigen or fragment thereof.” There is no defined structure for the recited autoantigen.
11. In contrast to the breadth of the claims, the specification describes particular chimeric autoantibody receptors comprising the extracellular domains of Dsg3. Specifically, the specification describes nucleic acids encoding a chimeric autoantibody receptor which comprises EC1-5, EC1-2, EC1-3, EC1-4, EC2-3, EC34, EC4-5, EC2-4, EC3-5 and EC2-5 (See pp. 53-58, for example). The Specification also discloses that these constructs were shown to kill anti-Dsg3 cells targeting a broad range of epitopes (See pp. 55-56); eliminated anti-Dg3 IgG+ cell in a mouse model (See pg. 68); and reduced AK23 tumor burden (See pg. 68).. However, there does not appear to be an adequate written description in the Specification as filed of the essential structural features of a generic ”autoantigen” or autoantigens that comprise any part of Dsg3 that provide for this activity. Furthermore, there does not appear to be an adequate written description in the Specification as filed of the essential structural features of the autoantibodies which would be the target of said chimeric autoantibody receptors. In contrast to the constructs described in the Specification, the only factors present in the instant claims are a very limited structure.
12. It is well known that minor structural differences even among structurally related compounds can result in substantially different biology, expression and activities. While it is known that amino acid substitutions are generally possible in any given protein, the positions within the protein's sequence where such amino acid substitutions can be made with a reasonable expectation of success are limited. Certain positions in the sequence are critical to the protein's structure/function relationship, e.g. such as various sites or regions directly involved in binding, activity and in providing the correct three-dimensional spatial orientation of binding and active sites. These regions can tolerate only relatively conservative substitutions or no substitutions (see Wells, 1990, Biochemistry 29:8509-8517; Ngo et al., 1994, The Protein Folding Problem and Tertiary Structure Prediction, pp. 492-495). While art-recognized procedures for designing and producing variants is known, such does not provide adequate written description of the active variants that may be constructed, since the art recognizes that function cannot be predicted from structure alone (Skolnick et al., 2000, Trends in Biotech. 18(1):34-39, especially p. 36 at Box 2).
13. In the instant case, there is insufficient guidance based on the reliance of disclosure of nucleic acids encoding a chimeric autoantibody receptor which comprises Dsg3 extracellular domains EC1-5, EC1-2, EC1-3, EC1-4, EC2-3, EC34, EC4-5, EC2-4, EC3-5 or EC2-5, to direct a person of skill in the art to select or to predict particular residues of the autoantigen as essential for binding Dsg3 autoantibodies. Accordingly, the distinguishing characteristics of the claimed genus are not described. The only adequately described species are nucleic acids encoding a chimeric autoantibody receptor which comprises Dsg3 extracellular domains EC1-5, EC1-2, EC1-3, EC1-4, EC2-3, EC34, EC4-5, EC2-4, EC3-5 or EC2-5. Accordingly, the specification does not provide adequate written description of the claimed genus.
14. Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
15. With the exception of the Dsg3 chimeric autoantibody receptors referred to above, the skilled artisan cannot envision the detailed chemical structure of the encompassed variants, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The product itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
16. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF's were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence.
17. Therefore, only nucleic acids encoding a chimeric autoantibody receptor which comprises Dsg3 extracellular domains EC1-5, EC1-2, EC1-3, EC1-4, EC2-3, EC34, EC4-5, EC2-4, EC3-5 or EC2-5, but not the full breadth of the claims, meets the written description provision of 35 U.S.C. §112, first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
Double Patenting
18. 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 claims at issue 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); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
19. 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
20. The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
21. Claims 1-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 10,301,370. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘370 recite a modified cell comprising a chimeric autoantibody receptor (CAAR) comprising an extracellular domain of Dsg1, Dsg3, or a fragment thereof. The claims also recite wherein the extracellular domain of Dsg3 comprises an amino acid sequence selected from SEQ ID NOs: 2-12 or 36, and wherein the CAAR comprises a CD8 alpha chain signal peptide, a CD8 alpha chain hinge and transmembrane domain, a CD37 intracellular signaling domain, or a CD3 zeta signaling domain. Therefore the instant claims are obvious over the claims of the ‘370 patent since the instant claims recite a nucleic acid which encodes the CAAR which is comprised in the cell recited in the claims of ‘370. It is noted that the instant application is not a divisional of the application that issued as the ‘370 patent, and therefore, the prohibition of double patenting for divisional applications does not apply (see 35 U.S.C. 121). The courts have pointed out that a “person of ordinary skill in the art is deemed to read the claim term not only in the context of the particular claim in which the disputed term appears, but in the context of the entire patent, including the specification.” ICU Med., Inc. v. Alaris Med. Sys., Inc., 558 F.3d 1368, 1374 (Fed. Cir. 2009)(emphasis added): Aquatex Indus., Inc. v. Techniche Solutions, 419 F.3d 1374, 1380 (Fed.Cir.2005); Phillips, 415 F.3d at 1313.
22. Therefore, instant claims 1-16 are obvious over the patented claims 1-16 of ‘370 which claims a cell comprising a CAAR that is encoded by the nucleic molecules of the instant claims.
23. Claims 1-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 11,407,802. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘802 recite a modified cell comprising a chimeric receptor comprising an extracellular domain of Dsg1, Dsg3, or a fragment thereof. The claims also recite wherein the extracellular domain of Dsg3 comprises an amino acid sequence selected from SEQ ID NOs: 2-12 or 36, and wherein the chimeric receptor comprises a CD8 alpha chain signal peptide, a CD8 alpha chain hinge and transmembrane domain, a CD37 intracellular signaling domain, or a CD3 zeta signaling domain. Therefore the instant claims are obvious over the claims of the ‘802 patent since the instant claims recite a nucleic acid which encodes the chimeric receptor which is comprised in the cell recited in the claims of ‘802. It is noted that the instant application is not a divisional of the application that issued as the ‘802 patent, and therefore, the prohibition of double patenting for divisional applications does not apply (see 35 U.S.C. 121). The courts have pointed out that a “person of ordinary skill in the art is deemed to read the claim term not only in the context of the particular claim in which the disputed term appears, but in the context of the entire patent, including the specification.” ICU Med., Inc. v. Alaris Med. Sys., Inc., 558 F.3d 1368, 1374 (Fed. Cir. 2009)(emphasis added): Aquatex Indus., Inc. v. Techniche Solutions, 419 F.3d 1374, 1380 (Fed.Cir.2005); Phillips, 415 F.3d at 1313.
24. Therefore, instant claims 1-16 are obvious over the patented claims 1-14 of ‘802 which claims a cell comprising a chimeric receptor that is encoded by the nucleic molecules of the instant claims.
25. Claims 1-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 11,407,803. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘802 recite a nucleic acid encoding a chimeric receptor comprising an extracellular domain of Dsg1, Dsg3, or a fragment thereof. The claims also recite wherein the extracellular domain of Dsg3 comprises an amino acid sequence selected from SEQ ID NOs: 2-12 or 36, and wherein the chimeric receptor comprises a CD8 alpha chain signal peptide, a CD8 alpha chain hinge and transmembrane domain, a CD37 intracellular signaling domain, or a CD3 zeta signaling domain. The claims also recite a vector comprising said nucleic acid. Therefore the instant claims are obvious over the claims of the ‘803 patent since the instant claims recite a genus of nucleic acid molecules which is overlapping in scope with the nucleic acid molecules recited in the claims of ‘803.
26. Claims 1-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 11,578,113. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘113 recite a method of treatment comprising administering a genetically modified cell which comprises a chimeric receptor comprising an extracellular domain of Dsg1, Dsg3, or a fragment thereof. The claims of ‘113 also recite wherein the extracellular domain of Dsg3 comprises an amino acid sequence selected from SEQ ID NOs: 2-12 or 36, and wherein the chimeric receptor comprises a CD8 alpha chain signal peptide, a CD8 alpha chain hinge and transmembrane domain, a CD37 intracellular signaling domain, or a CD3 zeta signaling domain. Therefore the instant claims are obvious over the claims of the ‘113 patent since the instant claims recite a nucleic acid which encodes the chimeric receptor which is comprised in the cell being administered in the claims of ‘113. It is noted that the instant application is not a divisional of the application that issued as the ‘113 patent, and therefore, the prohibition of double patenting for divisional applications does not apply (see 35 U.S.C. 121). The courts have pointed out that a “person of ordinary skill in the art is deemed to read the claim term not only in the context of the particular claim in which the disputed term appears, but in the context of the entire patent, including the specification.” ICU Med., Inc. v. Alaris Med. Sys., Inc., 558 F.3d 1368, 1374 (Fed. Cir. 2009)(emphasis added): Aquatex Indus., Inc. v. Techniche Solutions, 419 F.3d 1374, 1380 (Fed.Cir.2005); Phillips, 415 F.3d at 1313.
27. Therefore, instant claims 1-16 are obvious over the patented claims 1-21 of ‘113 which claims a method of administering a cell comprising a chimeric receptor that is encoded by the nucleic molecules of the instant claims.
Summary
28. No claim is allowed.
Advisory Information
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/JON M LOCKARD/Examiner, Art Unit 1647 August 15, 2026
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