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 .
Applicant's election with traverse of group 1, claims 81-82, drawn to a siglec-6 binding polypeptide, in the reply filed on 2/17/26, is acknowledged. Applicant has further elected SEQ ID NO: 25 as the species of CAR, IgG3 as the species of spacer, and 4-1BB as the species of costimulatory domain. Upon reconsideration, the restriction requirement between groups 1 and 2 is withdrawn.
Applicant's traversal is on the grounds it would not be an undue burden to examine all of the claims, citing MPEP 803. This is not found persuasive because undue burden is irrelevant to the restriction practice for cases filed under 35 U.S.C 371 (see MPEP Chapter 1800). Regardless, the search and examination of all the claims would be an undue burden. For example, a search for a product is more extensive than a method of making and using a product, since a product could be made or used by any number of methods and still be applicable prior art. Furthermore, method claims require consideration of factors such as timing, dosage and efficacy that are not necessarily relevant for product claims. It is an undue burden for the examiner to search and examine more than one invention.
The requirement is still deemed proper and is therefore made FINAL.
Claims 92-94 and 97-101 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Claims 81-91 and 95-96 are being acted upon.
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 82-91 and 95-96 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.
The phrase “such as” and "preferably" renders claims 82-91 and 95-96 indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). For the purposes of examination, the limitations are being interpreted as optional.
Claim 82 is indefinite since it recites options (a), (b), (c), without an “and” or an “or” between the options. Therefore, it is not clear if (a), (b), “and” (c), are required elements, or whether one could choose from (a), (b), “or” (c). Amendment to specify and “and” or an “or” between option (b) and (c) would be remedial.
Claim 83, 86, and 89-90 are indefinite in the recitation of a “set” of polynucleotides encoding the siglec-6 binding polypeptide. It is unclear what the set encompasses. For example a set would be understood encompass more than 1 separate polynucleotide molecule. However, the “set” of the instant claims encodes a siglec-6 binding CAR, which is a single polypeptide chain. Do the claims intend to encompass sets of polynucleotides encoding CAR that have more than one polypeptide chain? It is unclear how the “set” encodes the polypeptide. The scope of the claim is unclear and indefinite.
The term “minimal” DNA expression cassette in claim 87 is a relative term which renders the claim indefinite. The term “minimal” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim 87 contains the trademark/trade name Sleeping BeautyTM or PiggyBacTM. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a transposon donor DNA molecule and, accordingly, the identification/description is indefinite.
Regarding claim 89, the recitation of a polynucleotide encoding “the same” is unclear and indefinite. Amendment to recite encoding “the siglec-6 binding polypeptide” would be remedial.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 95 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 95 is directed to a product, an immune cell, that is obtainable by the method of claim 92. However, patentability of a product does not depend on its method of production. In other words, the process steps of claim 92 are not required in claim 95, and claim 95 would encompass structurally identical immune cells even if made by a different process. Therefore, claim 95 does not require all the limitations of the claim from which it depends. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
The following is a quotation of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 81-91 and 95-96 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. Specifically, there is insufficient written description to demonstrate that applicant was in possession of the claimed genus of extracellular ligand binding domain comprising “an amino acid sequence shown in”, for example SEQ ID NO: 25, or “an amino acid sequence having at least 90% identity to an amino acid sequence shown in”, for example, SEQ ID NO: 25.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See MPEP 2163.
The instant claims are drawn to a siglec-6 binding polypeptide comprising a sigle-6 binding CAR, wherein the CAR comprises an extracellular ligand binding domain comprising “an amino acid sequence shown in”, for example SEQ ID NO: 25, or “an amino acid sequence having at least 90% identity to an amino acid sequence shown in”, for example, SEQ ID NO: 25. SEQ ID NO: 25 is the sequence of a JML-1 scFv, and comprises a VH comprising 3 CDR sequences and a VL comprising 3 CDR sequences. For example, a single CDR, could be within the scope of “an amino acid sequence shown in” SEQ ID NO: 25. The claims also encompass sequences having 90% identity to SEQ ID NO: 25, which would encompass numerous additions, deletions or substitutions to the scFV in SEQ ID NO: 25, including in the CDR regions.
The state of the art is such that the 6 CDRs of an antibody are critically involved in antigen binding, that even single amino acid changes can alter antigen specificity of binding, and that CDR mutations are unpredictable in terms of affinity, specificity, and solubility, and are also context dependent (see Hall, 1992, and Rabia, 2018). The only species of extracellular ligand binding domain that functions to bind to siglec-6 disclosed by the instant specification is SEQ ID NO: 25. This is not sufficiently representative of the genus of different ligand binding domains that function to bind to siglec-6, which would encompass those having a single CDR of SEQ ID NO: 25 (i.e. “an amino acid sequence” shown in SEQ ID NO: 25) or those varying by up to 10% in any region shown in SEQ ID NO: 25, including the CDRs.
The instant application has not provided a sufficient description showing possession of the necessary functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the genus of extracellular binding domains. Further, the Court has interpreted 35 U.S.C. §112, first paragraph, to require the patent specification to “describe the claimed invention so that one skilled in the art can recognize what is claimed. Enzo Biochem, Inc. v. Gen-Probe Inc, 63 USPQ2d 1609 and 1618 (Fed. Cir. 2002).
In evaluating whether a patentee has fulfilled this requirement, our standard is that the patent’s “disclosure must allow one skilled in the art ‘to visualize or recognize the identity of’ the subject matter purportedly described.” Id. (quoting Regents of Univ. of Cal. v. Eli Lilly & Co., 43 USPQ2d 1398 (Fed Cir. 1997)).
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear 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.)
Also, it is noted that the Court has held that the disclosure of screening assays and general classes of compounds was not adequate to describe compounds having the desired activity: without disclosure of which peptides, polynucleotides, or small organic molecules have the desired characteristic, the claims failed to meet the description requirement of § 112. See University of Rochester v. G.D. Searle & Co., lnc., 69 USPQ2d 1886,1895 (Fed. Cir. 2004).
Meeting the written description threshold requires showing that the applicant was in “possession” of the claimed invention at the time of filing. Vas-Cath, 935 F.2d at 1563-1564. Support need not describe the claimed subject matter in exactly the same terms as used in the claims. Eiselstein v. Frank, 52 F.3d 1035, 1038 (Fed. Cir. 1995). This support cannot be based on obviousness reasoning – i.e., what the written description and knowledge in the art would lead one to speculate as to modifications the inventor might have envisioned, but failed to disclose. Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997). Ariad points out, the written description requirement also ensures that when a patent claims a genus by function, the specification recites sufficient materials to accomplish that function - a problem that is particularly acute in biological arts." Ariad, 598 F.3d at 1352-3. Note the following Court Decisions regarding the written description of antibodies in the context of the current claims.
Thus, one of skill in the art would conclude that the specification fails to provide adequate written description to demonstrate that Applicant was in possession of the claimed genus. See Eli Lilly, 119 F. 3d 1559, 43, USPQ2d 1398.
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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 81-91 and 95-96 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by WO 2020/254591.
The applied reference has a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
WO 2020/254591 teaches a siglec-6 binding CAR comprising a Sigle-6 binding scFv having SEQ ID NO: 14, which is identical to SEQ ID NO: 25 of the instant application, and further comprising an IgG3 spacer, a transmembrane domain, and an intracellular domain (see pages 9-10, 27, and 52 in particular). WO 2020/254591 teaches an immune cell, such as a T cell, expressing the CAR from a polynucleotide encoding the CAR and pharmaceutical compositions thereof (see page 12, in particular). WO 2020/254591 teaches CAR comprising a CD28 transmembrane domain and a 4-1BB and CD3 zeta intracellular domain (See pages 38 and 96, in particular). WO 2020/254591 teaches a polynucleotide encoding the CAR, expression vectors comprising said polynucleotide, and wherein the vector is a lentiviral vector or a non-viral vector circularized vector (i.e. minimal DNA expression cassette, see page 60 and 127-128). WO 2020/254591 teaches expression vectors having a transposon with flanking IR/DR segments in the 5’ and 3’ direction (see page 60, and 127-128, in particular).
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.
Claim 81-91 and 95-96 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 20120121504, in view of US 20160051651, and as evidenced by Chang, 2018 (of record).
The ‘504 publication teaches a CAR comprising a scFv extracellular binding domain that targets B-CLL, said scFv having a VH of SEQ ID NO: 18 and a VL of SEQ ID NO: 1, wherein the CAR further comprising an IgG hinge (i.e. spacer), a transmembrane domain, and an intracellular TCR signaling domain including CD3 and 4-1BB (see paragraphs 27-30 and 41, in particular). The ‘504 publication teaches a T cells expressing said CAR (i.e. immune cells comprising a polynucleotide encoding said CAR, see paragraph 41, in particular). The ‘504 publication teaches that said VH/VL are from antibody JML-1. As evidenced by Chang, the JML-1 antibody binds to Siglec-6 on B-CLL. Thus, binging Siglec-6 is an inherent or latent property of the CAR taught by the ‘504 publication. The ‘504 publication teaches pharmaceutical compositions (see paragraphs 51-55, in particular).
The reference differs from the claimed invention in that it does not explicitly teach SEQ ID NO: 25, a CD28 transmembrane domain, that the CD3 domain is CD3-zeta, or the details of the polynucleotide/expression vector for expressing the CAR.
The ‘651 publication teaches CAR that target CLL cells having an scFv, wherein the scFv can be constructed in an orientation of heavy chain variable region-linker-light chain variable region, wherein the linker can be a Gly4-Ser linker with 3 repeats (See paragraph 13 and 432, in particular). The ‘651 publication teaches that transmembrane domains for use in CAR can include CD28 transmembrane domain and that the preferred CD3 intracellular domain is CD3 zeta (See paragraphs 20 and 447, in particular). The ‘651 publication teaches that CAR can be expressed from a polynucleotide using lentivirus vectors or non-viral vectors, such as a plasmids or minicircles (see paragraphs 55-56 and 613, in particular). The ‘651 publication teaches that the polynucleotides and expression vectors can comprise a transposon with inverted repeats flanking the CAR (i.e. flanking elements in 5’ direction and 3’ direction and a nucleotide encoding a left IR/DR, a polynucleotide encoding the CAR, and a nucleotide encoding a right IR/DR, see paragraphs 568-575, in particular).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to construct the scFv in the VH-linker-VL orientation with a Gly4Ser linker with 3 repeats, as taught by the ‘651 publication, as the scFv in the CAR of the ‘504 publication. The ordinary artisan at the time the invention was made would have been motivated to do so with a reasonable expectation of success, because the ‘651 publication teaches that doing so is effective in construction of CAR that target CLL. Furthermore, doing so would involve choosing among a finite number of predictable options which could be pursued with a reasonable expectation of success. A person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense (see KSR International Co. V. Telefex Inc 82 USPQ2d 1385). Constructing a scFV with SEQ ID NO: 18 (VH) Gly4Ser 3 repeat linker, SEQ ID NO: 1 (VL) would result in an a sequence 100% identical to SEQ ID NO: 25 of the instant application (See attached alignment). Furthermore selecting from known transmembrane and CD3 signaling domains for use in CAR or expression vectors for expressing a CAR in an immune cells would also involve choosing among a finite number of predictable options which could be pursued with a reasonable expectation of success.
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 81-91 and 95-96 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 52-56, 68-71 of copending Application No. 17/619,569 in view of US 20120121504, US 20160051651, and Chang, 2018..
The ’569 application claims a CAR comprising an extracellular antigen binding domain, a spacer domain, a transmembrane domain, and an intracellular domain, wherein the spacer domain is an IgG3 hinge region. The ‘569 application claims that the extracellular ligand binding domain is an scFv. The ‘569 application claims an immune cell, preferably a T cell, expressing said CAR. The ‘569 application claims that the scFv binds to Siglec-6.
Although not specifically claimed in the ‘569 application, it would be obvious to use the Siglec-6 scFv made obvious by the ‘504 publication, the ‘651 publication, and Chang, as set forth above, as the Siglec-6 scFv. The ordinary artisan at the time the invention was made would have been motivated to do so with a reasonable expectation of success, because the ‘504 publication teaches that the scFv is effective for targeting CLL, and as taught by Chang, it binds Siglec-6. Furthermore, constructing the scFV in Vh-linker-VL orientation, expression from a vector, such as a non-viral vector or transposon, or using CD28 transmembrane domain, 4-1BB and CD3 zeta intracellular domain as taught by the ‘504 publication and the ‘651 publication would involve choosing among a finite number of predictable options which could be pursued with a reasonable expectation of success. A person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense (see KSR International Co. V. Telefex Inc 82 USPQ2d 1385).
This is a provisional nonstatutory double patenting rejection.
No claim is allowed.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached on 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Amy E. Juedes
Patent Examiner
Technology Center 1600
/AMY E JUEDES/Primary Examiner, Art Unit 1644