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 .
Nucleotide and/or Amino Acid Sequence Disclosures
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.831-1.834 because it does not contain a “Sequence Listing XML” as a separate part of the disclosure. A “Sequence Listing XML” is required because the claims and specification both recite numerous SEQ ID NOs.
A reissue application that discloses nucleotide and/or amino acid sequences must comply with the sequence rules (37 CFR 1.831 - 37 CFR 1.839 for reissue applications filed on or after July 1, 2022). See MPEP § 2412 et seq. for detailed information pertaining to the submission of "Sequence Listing XMLs" and MPEP § 2422.03 et seq. for detailed information pertaining to the submission of "Sequence Listings".
Claim Objections
The 11/10/22 preliminary amendment to the claims is objected to because it identifies material to be deleted using strikethrough, not single brackets as 37 CFR 1.173(d)(1) requires. See MPEP 1453. A compliant claim listing is required in response to this Office action.
In addition, claim 2 contains an extraneous word “a” before “Fab fragments” at line 2. Claim 6 contains an extraneous space within “CD16” at line 3. Claim 7 uses a semicolon, not a comma, after CD8[Symbol font/0x61] at line 2. Claims 11 and 13 should begin with the word “The” for consistency with claims 2-10, 12, and 14-24.
Assignee’s Consent to Reissue
The 11/10/22 consent to reissue signed by Seung Shin Yu, CTO, is defective because it was neither signed by a person with apparent authority as defined in MPEP 325(V) nor signed by a person authorized to act on behalf of the assignee at the time of signing. MPEP 325(V) recognizes that persons with “apparent authority” to sign on behalf of an organization include officers of that organization, e.g., its chief executive officer, president, vice-president, secretary, or treasurer. Consenter Yu is none of these, being designated only as “CTO.” There is also nothing in the record to indicate that consenter Yu was authorized to act on behalf of the assignee; compare assignment document, identifying Mark E. Rogel as being so authorized.
This matter would be overcome by submission of a replacement consent of the assignee signed by either a person authorized to act on behalf of the assignee; an officer of the assignee; or a patent practitioner already appointed power of attorney at the time of signing.
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.
Claim 21 is 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 21 depends from claim 20 and refers to “the spacer region polypeptide.” Claim 20 only recites a spacer region, not a spacer region polypeptide. The antecedent basis for claim 21’s limitation is unclear.
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 1-4, 6-10, 13-17, and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (WO 2015054600; IDS) in view of Zhao et al. (WO 2013040557; IDS) and Hong et al. (US 20080279847; IDS).
Zhang teaches a chimeric antigen receptor (CAR) comprising an extracellular ligand binding domain that binds to sialyl Tn (STn) to kill tumor cells. (Pages 6, 29, and 69.) Zhang teaches CARs can comprise any of the structures of WO 2013040557 (Zhao). (Page 69.)
Zhao teaches CARs comprising a CD8[Symbol font/0x61] transmembrane domain, the CD137 (4-1BB co-stimulatory signaling domain, the CD3z primary signaling domain, and the CD8[Symbol font/0x61] hinge region. (Page 21.)
Hong teaches anti-STn antibodies that comprise SEQ ID NOs: 15 and 161 (Hong’s SEQ ID NOs: 21 and 4, respectively; paragraph 42.). Hong teaches that his antibody is useful for treating cancer. (Paragraphs 16, 78, 87, 91, 92, and 112.)
It would have been obvious to make an STn-targeting CAR comprising the heavy and light chains of Hong’s antibody with a CD8[Symbol font/0x61] transmembrane domain, CD137 (4-1BB) co-stimulatory signaling domain, CD3z primary signaling domain, and CD8[Symbol font/0x61] hinge region. Zhang and Hong both teach that STn antibodies are useful for treating cancer. As such, Hong’s antibody and Zhang’s antibody were recognized in the art as functional equivalents; substituting one for another would have been prima facie obvious. See MPEP 2144.06(II). One of skill in the art would accordingly have been motivated to use art-identified antibodies in Zhao’s CAR constructs in order to target STn in cancer.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (WO 2015054600) in view of Zhao et al. (WO 2013040557) and Hong et al. (US 20080279847) as applied to claims 1-4, 6-10, 13-17, and 25, above, and further in view of Hong 2 (US 8119132; reference A) as evidenced by Goshorn (US 20030143233; reference B).
The teachings of Zhang, Zhao, and Hong are relied upon as above.
Zhang, Zhao, and Hong do not teach that the variable light-chain sequence is SEQ ID NO:23 or that the variable heavy-chain sequence is SEQ ID NO:24.
Hong 2 teaches humanized antibodies to TAG-72. Hong teaches that the variable light-chain sequence is SEQ ID NO:23 and that the variable heavy-chain sequence is SEQ ID NO:24 (Hong 2’s SEQ ID NOs: 21 and 4, respectively).2 Goshorn is cited solely as evidence that sialyl-Tn is a disaccharide epitope inherently present on TAG-72. (Paragraph 117.)
It would have been obvious to make an STn-targeting CAR comprising the heavy and light chains of Hong 2’s antibody with a CD8[Symbol font/0x61] transmembrane domain, CD137 (4-1BB) co-stimulatory signaling domain, CD3z primary signaling domain, and CD8[Symbol font/0x61] hinge region. Zhang and Hong 2 both teach that STn antibodies are useful for treating cancer. As such, Hong 2’s antibody and Zhang’s antibody were recognized in the art as functional equivalents; substituting one for another would have been prima facie obvious. See MPEP 2144.06(II). One of skill in the art would accordingly have been motivated to use art-identified antibodies in Zhao’s CAR constructs in order to target STn in cancer.
Claims 11 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (WO 2015054600) in view of Zhao et al. (WO 2013040557) and Hong et al. (US 20080279847) as applied to claims 1-4, 6-10, 13-17, and 25, above, and further in view of Finer (WO 2014099671; reference N).
The teachings of Zhang, Zhao, and Hong are relied upon as above.
Zhang, Zhao, and Hong do not teach that the co-stimulatory signaling domain is from CD28 or CD134.
Finer teaches that CARs may contain co-stimulatory signaling domains from any of CD28, CD134, and CD137 (4-1BB). (Page 2, lines 32-33; page 7, lines 4-9.) Finer teaches that CARs containing these co-stimulatory signaling domains effectively direct antitumor activity in animal models and cancer patients. (Page 7, lines 4-9.)
It would have been obvious to the person of ordinary skill in the art to substitute Finer’s co-stimulatory signaling domain from CD28 or CD134 for Zhao’s co-stimulatory signaling domain from CD137 (4-1BB) because Finer teaches that all three of these can be used in CARs containing the elements of Zhao’s CAR to treat cancer. See also MPEP 2144.06(II) (prima facie obvious to substitute art-recognized equivalents for each other for same purpose).
Claims 18 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (WO 2015054600) in view of Zhao et al. (WO 2013040557) and Hong et al. (US 20080279847) as applied to claims 1-4, 6-10, 13-17, and 25, above, and further in view of Morgan (WO 2015164759; reference O).
Morgan is prior art under 35 U.S.C. 102(a)(1) inside the grace period because it was published on 10/29/15, less than one year before the filing of US provisional application 62/317,950 on 4/4/16. Applicant also claims benefit of a Korean application filed 8/31/15, but no English-language translation has been made of record in this application, so it cannot disqualify Morgan under 102(a)(1). Morgan is also prior art under 35 U.S.C. 102(a)(2) because it names another inventor relative to this application and was effectively filed before it.
The teachings of Zhang, Zhao, and Hong are relied upon as above.
Zhang, Zhao, and Hong do not teach that the hinge region polypeptide comprises a hinge region of PD1 or CD152.
Morgan teaches that CARs may contain hinge region polypeptides comprising hinge regions from any of CD8[Symbol font/0x61], PD1, and CD152. (Page 4, lines 1-8.) Morgan teaches that CARs containing these hinge regions are useful in treating cancer. (Page 1, lines 15-19.)
It would have been obvious to the person of ordinary skill in the art to substitute Morgan’s hinge region from PD1 or CD152 for Zhao’s hinge region from CD8[Symbol font/0x61] because Morgan teaches that all three of these can be used in CARs containing the elements of Zhao’s CAR to treat cancer. See also MPEP 2144.06(II) (prima facie obvious to substitute art-recognized equivalents for each other for same purpose).
Claims 20-23 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (WO 2015054600) in view of Zhao et al. (WO 2013040557) and Hong et al. (US 20080279847) as applied to claims 1-4, 6-10, 13-17, and 25, above, and further in view of Jensen et al. (US 20150306141; on IDS).
The teachings of Zhang, Zhao, and Hong are relied upon as above.
Zhang, Zhao, and Hong do not teach that the CAR further comprises a spacer region, for example one comprising CH2 and CH3 regions of IgG1, IgG4, or IgD, or a signal peptide, for example one from IgG1, CD8[Symbol font/0x61], or human GM-CSF receptor alpha.
Jensen teaches CARs can comprise a spacer region of IgG4 Fc (which contains hinge-CH2-CH3) and a signal peptide from CD8[Symbol font/0x61]. (Pages 2, 11, 12, and Figures.)
It would have been obvious to make a STn-signaling CAR comprising the CDRs of Hong’s antibody, a CD8[Symbol font/0x61] transmembrane domain, the CD137 (4-1BB) co-stimulatory signaling domain, the CD3z primary signaling domain, the CD8[Symbol font/0x61] hinge or IgG4 hinge with CH2-CH3 and the CD8[Symbol font/0x61] signal peptide. Notably, Jensen teaches these domains are commonly included in CARs to facilitate function, so one of skill in the art would have found it obvious to include these art-recognized domains in producing a CAR targeting STn. The combination would have been expected to yield predictable results. See MPEP 2143(I) (simple combination).
Allowable Subject Matter
Claim 24 is objected to as being dependent upon a rejected base claim, but it would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Maintenance Fees
Applicant is reminded of the requirement to pay all applicable maintenance fees on the original patent. See MPEP 1415.01.
Duty to Disclose
Applicant is reminded of the continuing obligation under 37 CFR 1.178(b), to timely apprise the Office of any prior or concurrent proceeding in which Patent No. 11,279,769 is or was involved. These proceedings would include any trial before the Patent Trial and Appeal Board, interferences, reissues, reexaminations, supplemental examinations, and litigation.
Applicant is further reminded of the continuing obligation under 37 CFR 1.56, to timely apprise the Office of any information which is material to patentability of the claims under consideration in this reissue application.
These obligations rest with each individual associated with the filing and prosecution of this application for reissue. See also MPEP §§ 1404, 1442.01 and 1442.04.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LORA E BARNHART DRISCOLL, whose telephone number is (571) 272-1928. The examiner can normally be reached M-F 7:00-4:00 p.m. ET.
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) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Patricia Engle, can be reached at (571) 272-6660. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Lora E Barnhart Driscoll/Patent Reexamination Specialist, Art Unit 3991
Conferees:
/KSO/
Patent Reexamination Specialist, Art Unit 3991
/Patricia L Engle/SPRS, Art Unit 3991
1 The amino-acid sequences in SEQ ID NOs:15 and 16 were obtained from underlying application 15/755,819. This fact does not obviate applicant’s responsibility to bring this reissue application into sequence compliance.
2 The amino-acid sequences in SEQ ID NOs:23 and 24 were obtained from underlying application 15/755,819. This fact does not obviate applicant’s responsibility to bring this reissue application into sequence compliance.