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 .
Priority
2. The instant application, filed on 05 May, 2023, claims domestic benefit to US provisional application no. 63/341,691, filed on 13 May, 2022.
Status of Application
3. The response filed on 08 September, 2023 has been entered in full. The application also has the claim set filed on 05 May, 2023 but the two claim sets are identical and no amendments or withdrawals have been made. Therefore, claims 1-40 are pending and are the subject of this Office Action.
Information Disclosure Statement
4. The information disclosure statement (IDS) submitted on 27 July, 2023 has been considered by the examiner.
5. The information disclosure statement (IDS) submitted on 11 October, 2023 has been considered by the examiner.
Claim Objections
6. Claims 1-9, 36, and 37 objected to because of the following informalities: The structure drawings in the claims are not aligned correctly (See example below with arrows) rendering them difficult to interpret. Appropriate correction is required.
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1: Example of Unaligned Structures
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.
7. Claims 1-9 and 29-35 are rejected under 35 U.S.C. 112(a), 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, at the time the application was filed, had possession of the claimed invention.
Claim 1 recites that the antibody, comprises a VH region comprised of HCDR1, HCDR2, and HCDR3 and a VL region comprised of LCDR1, LCDR2, and LCDR3. Each of the CDRs are recited as including 1-4 possible sequences. As such, claim 1 encompasses a genus of antibody structures which as limited by as little as a random combination of the sequences listed for each CDR.
The instant disclosure, however, does not describe a representative number of species of the claimed genus performing the claimed function , nor does the disclosure identify a structure function relationship that could be used to predictably identify which of the claimed amino acid sequences could be used in combination in order to arrive at an antibody with the claimed function.
The samples of the instant disclosure studied the combinations of Ab1, Ab2, Ab3, Ab4, Ab5, and Ab6 (Table 2a). The examples do not describe the use of any other species of the claimed genus of antibodies nor do the examples demonstrate a predictable structure-function correlation between antibody structure and binding function.
The state of the art around the effective filing date of the claimed invention also does not provide a representative number of species or a predictable structure-function relationship to support the full scope of the claimed genus.
For example, Chiu et al. (2019) Antibody Structure and Function: Basis for Engineering Therapeutics Antibodies 8(55); 1-80 teaches, that the antigen binding site is formed by the pairing of the Fab VH and VL with the N-terminal region designed as the Fv region and that the VL region is composed of CDR-L1, CDR-L2, and CDR-L3 and the VH region is composed of CDR-H1, CDR-H2, and CDR-H3. The CDR loops are determined by variability analysis and brought together form the antigen-binding site (page 4, paragraph 2). Further, Chiu teaches a canonical structure is defined by the loop length, the conformation of the loop, and the conserved amino acid residues within the hypervariable loop and FRs (page 5, paragraph 2). Based on these teachings, and person of ordinary skill in the art would not have been able to predictably identify which species of the instantly claimed genus would be capable of performing the claimed function.
Teixeira and Erasmus et al. (2021) Drug-like antibodies with high affinity, diversity and developability directly from next-generation antibody libraries mAbs 13(1) discusses similar teachings about how improving the stability and developability of a lead antibody is typically achieved by modifying the sequence which can be time consuming and often results in reduced affinity and how sequence-based liabilities may affect one or more characteristics (abstract). Further, Teixeria and Erasmus teaches antibody libraries needed to determine affinity binding (abstract). Based on these teaching, a person of ordinary skill in the art at the time of filing would have not been able to identify which species of the claimed genus would be capable of the claimed function.
Claims 2-9 and 29-35 are rejected due to their dependency on claim 1.
The scope of the claims is not enabled.
Claim Rejections - 35 USC § 103
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.
8. Claims 36 and 37 are rejected under 35 U.S.C. 103 as being unpatentable over AbbVie (WO2017210471, on record IDS 07/27/2023).
In regards to claim 36, AbbVie teaches a possibility of glucocorticoid receptor agonists in claim 24 and 26 which predict the features laid out in instant claim 36. Claim 24 of AbbVie teaches the possibility of claimed features such as the -CH2O- between the two benzene rings (x), the fluorene addition (R11b) and the -CH3 (Z) groups on the same benzene ring, and the -CH2OH group (R3) off of the five-carbon ring. Claim 26 of AbbVie (which depends on claim 24 of AbbVie) further, teaches the use of the linker and heterobifunctional group combination (R7b-3) claimed in instant claim 36. Thus, together the claims teach substitutions which would predict the structure of instant claim 36.
In regards to claim 37 AbbVie teaches the claimed structure as a possible addition to the glucocorticoid receptor agonist (paragraph 00528).
Thus, AbbVie teaches all of the structural components of the structures in claims 36 and 37. Therefore, a person of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to try the teachings and substitutions outline in AbbVie with a reasonable expectation of success to yield the glucocorticoid receptor antagonists and linkers recited in claims 36 and 37.
9. Claims 38-40 are rejected under 35 U.S.C. 103 as being unpatentable over AbbVie in view of Shinmi et al. One-Step Conjugation Method for Site-Specific Antibody-Drug Conjugates through Reactive Cysteine-Engineered Antibodies Bioconjugate Chemistry (27) 1324-1331 (hereafter Shinmi).
AbbVie teaches the compounds in claims 36 and 37, from which claims 38-40 depend on as outlined above in the 103 rejection and further teaches the attachment of these glucocorticoid compounds at cystine residues to TNF-α targeting antibodies to form an antibody drug conjugate (page 133, section 5). AbbVie fails to teach a synthesis of an Antibody drug conjugate wherein the TNF-α antibody drug conjugate is produced by reducing the TNF-α antibody wherein the antibody comprises one or more engineered cysteine residues, oxidizing the TNF- α antibody, and contacting the compound with the TNF- α antibody to produce the conjugate (claim 39).
Shinmi, however, teaches reducing the antibody Trastuzumab with engineered cysteine residue. followed by oxidizing the Trastuzumab antibody, and finally contacting the antibody with a drug compound to form a conjugate (Scheme 1A). Further Shinmi teaches using dithiothreitol for reduction and (L)-dehydroascorbic acid for oxidation (page 1329, col 2 lines 20-25).
Thus, AbbVie discloses creating a conjugate with the claimed compound and a TNF-α antibody, and Shinmi teaches reducing and then oxidizing an antibody with engineered cysteine residues for the purpose of creating an antibody drug conjugate. Therefore, a person of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to combine the compound and teachings of AbbVie with the method of Shinmi with a reasonable expectation of success to develop an TNF-α antibody drug conjugate.
Prior Art of Record
10. The prior art of record does not disclose an antibody that binds to TNF-α having a VH and a VL with all the enabled (outlined above) CDR combinations recited in claim 1 (see Table 2A of specification). Dependent claims 2-35 are therefore also free of the prior art.
The CDRs of SEQ ID NOs: 1-6 recited in claims 1 and 10 correspond to antibody Ab1 (Table 2A of specification). The VH and VL (SEQ IDs NOs: 9 and 10) of claim 11 and the HC and LC (SEQ IDs NOs: 9 and 10) of claim 12 further correspond to Ab1 (Table 3 of specification).
The CDRs of SEQ ID NOs: 1, 2, 13, 14, 5, and 15 recited in claims 1 and 13 correspond to antibody Ab2 (Table 2A of specification). The VH and VL (SEQ IDs NOs: 16 and 17) of claim 14 and the HC and LC (SEQ IDs NOs: 18 and 19) of claim 15 further correspond to Ab2 (Table 3 of specification).
The CDRs of SEQ ID NOs: 22, 23, 13, 4, 5, and 6 recited in claims 1 and 16 correspond to antibody Ab3 (Table 2A of specification). The VH and VL (SEQ IDs NOs: 24 and 8) of claim 19 and the HC and LC (SEQ IDs NOs: 25 and 10) of claim 22 further correspond to Ab2 (Table 3 of specification).
The CDRs SEQ ID NOs: 22, 23, 13, 14, 5, and 15 recited in claims 1 and 17 correspond to antibody Ab4 (Table 2A of specification). The VH and VL (SEQ IDs NOs: 24 and 8) of claim 20 and the HC and LC (SEQ IDs NOs: 25 and 19) of claim 23 further correspond to Ab4 (Table 3 of specification).
The CDRs SEQ ID NOs: 22, 23, 13, 14, 5, and 6 recited in claims 1 and 18 correspond to antibody Ab5 (Table 2A of specification). The VH and VL (SEQ IDs NOs: 24 and 27) of claim 21 and the HC and LC (SEQ IDs NOs: 25 and 28) of claim 24 further correspond to Ab5 (Table 3 of specification).
The CDRs SEQ ID NOs: 1, 2, 30, 31, 5, and 32 recited in claims 1 and 25 correspond to antibody Ab6 (Table 2A of specification). The VH and VL (SEQ IDs NOs: 33 and 34) of claim 26 and the HC and LC (SEQ IDs NOs: 35 and 36) of claim 27 further correspond to Ab2 (Table 3 of specification).
SEQ ID NO: 43 (QASQGIXNYLN) has Serine or Arginine for X at the amino acid position 6. This arginine embodiment corresponds to SEQ ID NO: 14 and the serine embodiment corresponds to SEQ ID NO: 4.
SEQ ID NO: 44 (QQYDXLPLT) has asparagine or lysine for X at the amino acid position 5. This asparagine embodiment corresponds to SEQ ID NO: 15 and the lysine embodiment corresponds to SEQ ID NO: 6.
Double Patenting
11. 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.
12. Claims 1-35 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-7, 10-19, 41-47, and 53-59 of copending Application No. 18/054,284 (11/10/2022 claim set) in view of AbbVie.
The sequence identifiers in the co-pending and instant claims correspond to the same sequences.
Co-pending claims 4 and 39 are directed to antibodies and antibody conjugates with CDRs as recited in instant claim 1. Co-pending claims 1-3, and 38 are directed to an antibody and an antibody conjugate as recited in instant claims 10-12. Co-pending claims 15-17 are directed to an antibody as recited in the antibody conjugate in instant claims 13-15. Co-pending claim 5 is directed to an antibody with CDRs as recited in instant claim 16. Co-pending claim 7 is directed to an antibody with CDRs as recited in instant claim 17. Co-pending claim 6 is directed to an antibody with CDRs as recited in instant claim 18. Co-pending claim 10 is directed to an antibody with a VH and VLs as recited in instant claims 19-21. Co-pending claim 11 is directed to an antibody with a HC and LCs as recited in instant claims 22-24. Co-pending claims 12-14 are directed to an antibody as recited in instant claims 25-27. Co-pending claims 18-19 has cysteines as in instant claim 28. Co-pending claims 41-42 are directed to a pharmaceutical composition as in instant claim 31. Co-pending claims 42-46 and 48-53 are directed to methods of treating autoimmune disease or an inflammatory disease in a subject as in instant claims 32-35. Antibodies of the instant claims would inherently possess the properties recited in co-pending claims 47 and 53-59.
It is noted that co-pending claim 4 encompasses the antibodies claimed in co-pending claims 5-7 and 10-14 and thus co-pending claims 39 recitation to an antibody conjugate encompasses these antibodies as well.
The co-pending application fails to teach the antibody drug conjugates of the instant claims; however, AbbVie teaches the components of the claimed drugs including the linkers and heterobifunctional groups (Claims 2, 6, 7, 24, and 26). Claims 2 and 24 of AbbVie teach the possibility of claimed features such as the -CH2O- between the two benzene rings (x), the fluorene addition (R11b) and the -CH3 (Z) groups on the same benzene ring, and the -CH2OH group (R3) off of the five-carbon ring. Claim 6 of AbbVie (which depends on claim 2 of AbbVie) further teaches the heterobifunctional groups of the instant claims. Further, claims 7 and 26 of AbbVie (which depends on claims 2 and 24 of AbbVie, respectively ) teach the use of the linker heterobifunctional group combinations (R7b-3 in claim 24) claimed in instant claims. AbbVie also teaches the attachment of these glucocorticoid receptor agonist to antibodies.
Thus, the copending application teaches the antibodies claimed in the instant application and AbbVie teaches the structures of the glucocorticoid receptor agonists in the claims (claims 2, 6, 7, 24, and 26). Further AbbVie teaches attaching the glucocorticoid receptor agonist to an antibody for a targeted therapeutic and improved disease treatment. Therefore, a person of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to combine the teachings of the copending application with the teachings in AbbVie with a reasonable expectation of success to develop a TNF-α targeting therapeutic for improved disease treatment.
This is provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
13. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
WO 2022/204108 (published 29 September 2022, filed 22 March 2022) appears to be related the instant application. The document discloses formulas IIIa (IIIa page 7), IIIb (IIIc page 8), and IIIc (IIIb page 8) of the instant application. The document also discloses preparations 1-4 (preparations 1-4 pages 18-20). It is not prior art against the instant claims.
WO 2023/086871 (published 19 May 2023, filed 10 November 2022) appears to be related to U.S. Application 18/054,284 (filed ). The document discloses antibodies Ab1- Ab6 of the instant application (Tables 1-2, page 26). It is not prior art against the instant claims.
14. Any inquiry concerning this communication or earlier communications from the examiner should be directed to DASIA A ALDARONDO whose telephone number is 571. The examiner can normally be reached on Monday – Thursday from 7:30am to 4:30pm and Fridays from 7am – 11am.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama, can be reached at telephone number 571. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/D.A.A/Examiner, Art Unit 1647 /JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647