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 .
DETAILED ACTION
The amendment filed November 25, 2025 in response to the Office Action of June 9, 2025 is acknowledged and has been entered.
Claims 81 and 95 have been amended.
Claims 81-100 are pending and under consideration as drawn to the elected invention.
The Objection set forth in the previous Office Action of June 9, 2025 is hereby withdrawn in view of the amendment on claim 95.
The Non-Statutory Double Patenting rejection over Appl. 16/575, 557, is withdrawn in view that the Application has been issued as US Patent No. 12,427,201 B2 (Pat. 201) (September 20, 2025) and applicant’s arguments. Because Pat. 201 has a later expiration date of March 1, 2041, the rejection is withdrawn. See also Ex parte Baurin, Appeal 2024-002920, Appl. No. 17/135,529 (PTAB Nov. 6, 2024),
The Non-Statutory Double Patenting rejection over Appl. 18/345,892, is withdrawn in view that the Application has been issued as US Patent No. 12,144,869 B2 (Pat. 869) and applicant’s arguments. Because Pat. 869 has a later expiration date of June 30, 2043, the rejection is withdrawn.
MAINTAINED REJECTIONS
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 81-100 are rejected under 35 U.S.C. 103 as being unpatentable over Thanos (Thanos et al., US 2015/0017187 A1, Publication Date: 2015-01-15, cited in IDS of 10/26/2023, of record).
Thanos teaches antibodies modified at two or more site-specific positions with non-natural amino acid residues. An antibody substituted with non-natural amino acid could have advantageous production yield, solubility, binding and/or activity ([0008]).
Thanos teaches the non-natural amino acid can comprise a functional group. The functional groups include amino, carboxy, acetyl, hydrazine, hydrazido, semicarbazido, sulfanyl, azido, tetrazine and alkynl ([0176]). Thanos teaches many non-natural amino acids comprise acetyl moiety ([0181], claim 18). Thanos teaches incorporation of para-azido-methyl phenylalanine and para-azido phenylalanine in antibodies (Examples 1-3, 6, 8,17 and 19).
Thanos teaches the antibody can be any polypeptide or multimeric polypeptide. The substitutions can occur at any position in any chain of the polypeptides ([0009]).
Thanos teaches non-natural amino acid substitution with K-AEK in the light chain framework region, such as K39 and K45 (Table 10).
Thanos teaches as set forth above, however, Thanos does not explicitly teach the position K42.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to make antibody with one or more non-natural amino acid substitution as light chain of an antibody, and try different amino acid at the framework region of the light chain, such as K42, because Thanos teaches: 1) any position in light chain can be substituted with a non-natural amino acid; 2) lysine can be replaced by a non-natural amino acid such as K-AEK in framework region of light chain. One of ordinary skill in the art would understand that incorporation of non-natural amino acid in the framework region would unlikely change the binding properties of the antibody, as recognized by applicant (see paragraph 4 on page 5 of the Remarks filed on 02/18/2025). The motivation would have been to expand the options of antibodies and to develop a potential better antibody for production yield, solubility, binding and/or activity. Given the limited number of amino acids in the framework region of a light chain, one or ordinary skilled in the art would have had a reasonable expectation of success to reach the claimed antibody because Thanos teaches detailed methods of making antibodies with incorporated non-natural amino acids in both heavy chain and light chains (e.g. Examples 6, 17, 19, and [0527]).
Thanos teaches polynucleotide coding antibody and expression vector comprising the DNA and routine antibody production methods ([453], [454], and [0525]).
Regarding claim 84, Thanos teaches monoclonal antibody, such as Trastuzumab (Table 10, on page 82).
Regarding claim 85, Thanos teaches that the antibody of any of the preceding claims that is of a class or subclass selected from the group consisting of IgA, IgA, IgA2, IgD, IgE, IgG, IgGl, IgG2, IgG3 and IgM (claim 16).
Regarding claim 86, Thanos teaches that the antibody can be a humanized antibody ([0429]).
Regarding claim 87, Thanos teaches the non-natural amino acid incorporation into an aglycosylated antibody (Example 9).
Regarding claim 88, 89, Thanos teaches antibody fragments, e.g. Fv, Fc, Fab, scFv (claim 17).
Regarding claim 90, Thanos teaches the method can be applied to bispecific antibodies ([0429] and [0430]).
Regarding claim 91, Thanos teaches pharmaceutical composition comprising the claimed antibody and a pharmaceutically acceptable carrier ([0432], [0433]).
Regarding claim 92-94, Thanos teaches polynucleotide coding antibody and expression vector comprising the DNA and routine antibody production methods ([453], [454], and [0525]).
Regarding claim 95, Thanos teaches methods of making antibodies with non-natural amino acid incorporation in heavy chain, light chain or both (Examples 1-3, 6, 8).
Regarding claim 96 and 97, Thanos teaches methods of incorporation of para-azido-methyl phenylalanine and para-azido phenylalanine in antibodies (Examples 6, 17, 19, and [0527]).
Regarding claim 98 and 99, Thanos teaches that both heavy chain and the light chain were synthesized by cell-free protein synthesis, from an E.coli strain ([0556], Example 17).
Regarding claim 100, Thanos teaches isolated antibody preparations have less than about 5%, less than about 4%, less than about 3%, less than about 2% or less than about 1% of contaminating proteins by weight ([0037]).
Response to Arguments
For the 103 rejection, Applicant argues:
Applicant respectfully submits that the Office is engaging in impermissible hindsight and has not provided a specific motivation why a person of skill would choose the K42 substitution when it is not taught or suggested, especially in light of all the other positions for which data is presented.
Applicant’s arguments have been fully considered but they are not persuasive. In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
In this case, as set forth above, Thanos teaches antibody substituted with non-natural amino acid could have advantageous production yield, solubility, binding and/or activity; any position in light chain can be substituted with a non-natural amino acid; lysine can be replaced by a non-natural amino acid such as K-AEK in framework region of light chain. One of ordinary skill in the art would understand that incorporation of non-natural amino acid in the framework region would unlikely change the binding properties of the antibody. The motivation would have been to expand the options of antibodies and to develop a potential better antibody for production yield, solubility, binding and/or activity.
Applicant further argues that Thanos does not show the data associated with K42 substitution:
As acknowledged by the Office, Thanos does not describe the K42 substitution. Thanos postulates substitutions at light chain residues LOOI, L003, LOOS, L007, L008, L009, L0l0, L016, L017, L018, L020, L022, L026, L027, L045, L058, L063, L065, L066, L070, L077, L079, and Ll07, according to the Kabat or Chothia numbering schemes. See Thanos at paragraph [0121]. Thanos also postulates additional substitutions at L138, L142, L143, L152, L171, L182, L188, L199, and L201 according to the EU numbering scheme. Id. at paragraph [0122].
However, Thanos only provides data regarding light chain residues S7 and T22 in combination with substitutions at various heavy chain positions. Id. at Table 4. Thanos discloses data regarding thermostability (Table 5) and cell killing ability for antibody conjugates with substitutions at S7 and T22 (Table 7).
Applicant submits that, based on the data presented in Thanos, a person of skill would not be motivated to make a substitution at K42 when they could make substitutions at positions S7 or T22 with the results described in Thanos.
Applicant submits that a person would be motivated to make a substitution at a site described by Thanos, rather than simply pick a new site to substitute a non-natural amino acid.
Applicant submits that a person of skill in the art would have no motivation to generate an antibody conjugate, with an antibody that has the recited K42 substitutions, out of the hundreds of possibilities disclosed in Thanos (including various combinations) in both the heavy and light chains.
Applicant’s arguments have been fully considered but they are not persuasive. Thanos not only provides data for S7 and T22 substitution, but also explicitly teaches that the substitution can be done in any position, in particular in the framework region of light chain. Given the limited number of amino acids in the framework region of a light chain, one or ordinary skilled in the art would have had a reasonable expectation of success to make more substitutions in the framework region of a light chain and to reach the claimed antibody because Thanos teaches detailed methods of making antibodies with incorporated non-natural amino acids in both heavy chain and light chains (e.g. Examples 6, 17, 19, and [0527]). One of ordinary skilled in the art would have had a reasonable expectation that the K42 substitution would generate an antibody with advantageous production yield, solubility, binding and/or activity, as taught by Thanos.
In the field of biological technology, no invention has absolute certainty of success before experimental tests. Thus, only a reasonable expectation of success (not absolute) would have motivated an artisan to make the claimed substitution. Given the teachings from references, an ordinary skilled in the art would have would have had a reasonable expectation of success in producing the claimed invention.
Therefore, the rejection is maintained for the reasons of record.
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.
U.S. Patent No. 11,708,413
Claims 81-89, and 91 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of U.S. Patent No. 11,708,413 (hereinafter, Pat. 413, corresponding Appl. No. 16/072,778, of record). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of Pat. 413 teach:
1. An antibody conjugate comprising an antibody that specifically binds to CD74 linked site-specifically to at least one payload moiety, wherein the antibody comprises a non-natural amino acid at a site selected from the group consisting of HC-F404, HC-K121, HC-Y180, HC-F241, HC-221, LC-T22, LC-S7, LC-N152, LC-K42, LC-E161, LC-D170, HC-S136, HC-S25, HC-A40, HC-S119, HC-S190, HC-K222, HC-R19, HC-Y52, and HC-S70,
wherein the payload moiety is covalently linked to the non-natural amino acid directly or via a linker, and wherein the antibody comprises three heavy chain CDRs and three light chain CDRs of a VH-VL pair selected from the group consisting of:…One of ordinary skilled in the art would quickly recognize that LC-K42 represents an amino acid position corresponding to K42 according to the Kabat or Chothia numbering scheme.
2. The antibody conjugate of claim 1, wherein the non-natural amino acid is selected from the group consisting of p-acetyl-L-phenylalanine, O-methyl-L-tyrosine, L-3-(2-naphthyl)alanine, 3-methyl-phenylalanine, O-4-allyl-L-tyrosine, 4-propyl-L-tyrosine, tri-O-acetyl-GlcNAcβ-serine, L-Dopa, fluorinated phenylalanine, isopropyl-L-phenylalanine, p-azido-L-phenylalanine, p-azidomethyl-L-phenylalanine, …. Thus, claims 1 and 2 of Pat. 413 reads on instant claim 1-3.
12. The antibody conjugate of claim 11, wherein the non-natural amino acid is para-azidomethylphenylalanine or p-azidomethyl-L-phenylalanine.
17. The antibody conjugate of claim 1, wherein the antibody is a monoclonal antibody. This reads on instant claim 84.
18. The antibody conjugate of claim 1, wherein the antibody is an IgA, an IgD, an IgE, an IgG, or an IgM. This reads on instant claim 85.
19. The antibody conjugate of claim 1, wherein the antibody is humanized or human. This reads on instant claim 86.
20. The antibody conjugate of claim 1, wherein the antibody is aglycosylated. This reads on instant claim 87.
21. The antibody conjugate of claim 1, wherein the antibody is an antibody fragment. This reads on instant claim 88.
22. The antibody conjugate of claim 21, wherein the antibody fragment is selected from an Fv fragment, a Fab fragment, a F(ab′)2 fragment, a Fab′ fragment, an scFv (sFv) fragment, and an scFv-Fc fragment. This reads on instant claim 89.
28. A pharmaceutical composition comprising the antibody conjugate of claim 1 and a pharmaceutically acceptable carrier. This reads on instant claim 91.
Claims 90, 92-100 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 U.S. Patent No. 11,708,413 (hereinafter, Pat. 413, corresponding Appl. No. 16/072,778, of record) as applied to claims 81-89 and 91 in view of Thanos (Thanos et al., US 2015/0017187 A1, Publication Date: 2015-01-15, cited in IDS of 10/26/2023, of record).
The claims of Pat. 413 teaches instant claims 81-89 and 91 as set forth above. However, the claims of Pat. 413 do not explicitly teach, bispecific antibody, polynucleotide, vector, host cells, or method of making the antibody with cell-free system.
Thanos teaches antibodies modified at two or more site-specific positions with non-natural amino acid residues. An antibody substituted with non-natural amino acid could have advantageous production yield, solubility, binding and/or activity ([0008]).
Thanos teaches the antibody can be any polypeptide or multimeric polypeptide. The substitutions can occur at any position in any chain of the polypeptides ([0009]).
Regarding claim 90, Thanos teaches the method can be applied to bispecific antibodies ([0429] and [0430]).
Thanos teaches the method can be applied to bispecific antibodies ([0429] and [0430]).
Thanos teaches polynucleotide coding antibody and expression vector comprising the DNA and routine antibody production methods ([453], [454], and [0525]).
Thanos teaches the antibody comprise a heavy chain of a type selected from the group consisting of α, µ, ε ([0077]). And the antibody comprises a light chain of a type selected from the group consisting of λ, and κ.
Thanos teaches the non-natural amino acid can comprise a functional group. The functional groups include amino, carboxy, acetyl, hydrazine, hydrazido, semicarbazido, sulfanyl, azido, tetrazine and alkynl ([0176]). Thanos teaches many non-natural amino acids comprise acetyl moiety ([0181], claim 18). Thanos teaches incorporation of para-azido-methyl phenylalanine and para-azido phenylalanine in antibodies (Examples 1-3, 6, 8,17 and 19).
Regarding claim 91, Thanos teaches pharmaceutical composition comprising the claimed antibody and a pharmaceutically acceptable carrier ([0432], [0433]).
Regarding claim 92-94, Thanos teaches polynucleotide coding antibody and expression vector comprising the DNA and routine antibody production methods ([453], [454], and [0525]).
Regarding claim 95, Thanos teaches methods of making antibodies with non-natural amino acid incorporation in heavy chain, light chain or both (Examples 1-3, 6, 8).
Regarding claim 96 and 97, Thanos teaches methods of incorporation of para-azido-methyl phenylalanine and para-azido phenylalanine in antibodies (Examples 6, 17, 19, and [0527]).
Regarding claim 98 and 99, Thanos teaches that both heavy chain and the light chain were synthesized by cell-free protein synthesis, from an E.coli strain ([0556], Example 17).
Regarding claim 100, Regarding claim Thanos teaches isolated antibody preparations have less than about 5%, less than about 4%, less than about 3%, less than about 2% or less than about 1% of contaminating proteins by weight ([0037]).
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to make an antibody conjugate as taught by the claims of Pat. 413, and based on the teachings from Thanos, one of ordinary skilled in the art would have known to make bispecific antibody-conjugate, polynucleotide, vector, host cells, or using a cell-free system to make the antibody as taught by Thanos, doing so would generate a multifunctional antibody which can have advantageous production yield, solubility, binding and/or activity, more than one payload molecule, as recognized by Thanos ([0008] and [0291]). One or ordinary skilled in the art would have had a reasonable expectation of success because Thanos teaches detailed methods of making antibodies with incorporated non-natural amino acids in both heavy chain and light chains (e.g. Examples 6, 17, 19, and [0527]).
Response to Arguments
For this Double Patenting rejection, Applicant argues:
For claims 81-89 and 91, Applicant respectfully requests an abeyance for the rejection, until all other rejections have been overcome. At that time, Applicant will consider filing a Terminal Disclaimer over U.S. Patent No. 11,708,413.
For claims 90 and 92-100, Thanos et al. is now patented as US Patent No. 9,764,039 B2, and independently cited in a rejection below, (hereinafter referred to as the "'039" patent).
Applicant’s arguments have been fully considered but they are not persuasive because the claims of the instant application are still obvious in view of the patented claims and Thanos and a terminal disclaimer has not been filed. Therefore, the rejections above are maintained for the reasons of record.
Application No. 17/276,757
Claim 81-89 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 5, 8-11, 14-17, 22, 30, 31, 33, 34, 36-45 of copending Application No. 17/276,757 (hereinafter Appl. 757, US 2022/0047716 A1, of record). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of Appl. 757 teach:
1. A kit for treating cancer in a subject comprising:(a) an effective dose of an antibody drug conjugate comprising an antibody of the IgG class or an antibody fragment thereof that specifically binds to folate receptor alpha (FOLR1) linked site-specifically to at least one payload moiety, wherein the antibody comprises one or more non-natural amino acids at sites selected from the group consisting of: HC-F404, HC-K121, HC-Y180, HC-F241, HC-221, LC- T22, LC-S7, LC-N152, LC-K42, LC-E161, LC-D170, HC-S136, HC-S25, HC-A40, HC-Si19,HC-S190, HC-K222, HC-R19, HC-Y52, or HC-S70, according to the Kabat, Chothia, or EU numbering scheme; … and (b) an effective dose of one or more PD-1 or PD-L1 inhibitors, wherein the one or more PD-1 or PD-L1 inhibitors comprise a small molecule blocker of the PD-1 or PD-L1 pathway, or wherein the one or more PD-1 or PD-L1 inhibitors comprise an antibody that inhibits PD-1 or PD-L1 activity.
8. The composition of claim 1, wherein the one or more non- natural amino acids is selected from the group consisting of …, p-azido-methyl-L-phenylalanine, …, and p-propargyloxy- phenylalanine. These would read instant claims 81-83, 85, and 88.
17. The kit of claim 16, wherein the antibody or antibody fragment thereof that specifically binds to folate receptor alpha (FOLR1) comprises one or more non-natural amino acids at sites selected from the group of: HC-F404, HC-Yl80, and LC-K42 according to the Kabat or EU numbering scheme of Kabat.
22. The composition of claim 17, wherein one or both non-natural amino acids is selected from the group consisting of para-azidomethylphenylalanine and p-azido-methyl-L-phenylalanine. These would read instant claims 81-83, 85, and 88.
31. The kit of claim 1, wherein the antibody … is a monoclonal antibody. This reads on instant claim 84.
33. The kit of claim 1, wherein the antibody or antibody fragment thereof that specifically binds to folate receptor alpha (FOLR1) is humanized or human. This reads on instant claim 86.
34. The kit of claim 1, wherein the antibody or antibody fragment thereof that specifically binds to folate receptor alpha (FOLR1) is aglycosylated. This reads on instant claim 87.
36. The kit of claim 35, wherein the antibody fragment is selected from an Fv fragment, a Fab fragment, a F(ab')2 fragment, a Fab' fragment, an scFv (sFv) fragment, and an scFv-Fc fragment. This reads on claims 88 and 89.
45. The kit of claim 1, further comprising a pharmaceutically acceptable carrier administered to a subject with the effective dose of the antibody drug conjugate, the effective dose of one or more PD-1 or PD-L1 inhibitors, or both.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 90-100 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 5, 8-11, 14-17, 22, 30, 31, 33, 34, 36-45 of copending Application No. 17/276,757 (hereinafter Appl. 757, US 2022/0047716 A1, of record) as applied to claims 81-89 above, and in view of Thanos (Thanos et al., US 2015/0017187 A1, Publication Date: 2015-01-15, cited in IDS of 10/26/2023, of record).
The claims of Appl. 757 teaches as set forth above. However, the claims of Appl. 757 do not explicitly teach, bispecific antibody, pharmaceutical composition, polynucleotide, vector, host cells, or method of making the antibody with cell-free system.
Thanos teaches as set forth above.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to make an antibody conjugate as taught by the claims of Appl. 757, and based on the teachings from Thanos, one of ordinary skilled in the art would have known to make bispecific antibody-conjugate, polynucleotide, vector, host cells, or using a cell-free system to make the antibody as taught by Thanos, doing so would generate a multifunctional antibody which can have advantageous production yield, solubility, binding and/or activity, more than one payload molecule, as recognized by Thanos ([0008] and [0291]). One or ordinary skilled in the art would have had a reasonable expectation of success because Thanos teaches detailed methods of making antibodies with incorporated non-natural amino acids in both heavy chain and light chains (e.g. Examples 6, 17, 19, and [0527]).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
For this Double Patenting rejection, Applicant argues:
For claims 81-89, applicant argues by citing MPEP § 804(I)(B)(1)(b)(i): “If a provisional nonstatutory double patenting rejection is the only rejection remaining in an application having the earlier patent term filing date, the examiner should withdraw the rejection in the application having the earlier patent term filing date and permit that application to issue as a patent, thereby converting the provisional nonstatutory double patenting rejection in the other application into a nonstatutory double patenting rejection upon issuance of the patent."(emphasis added).
For claims 90-100, applicant argues that Thanos et al. does not remedy the deficiencies of the '757 application.
Applicant’s arguments have been fully considered but they are not persuasive because the claims of the instant application are still obvious in view of the co-pending claims and a terminal disclaimer has not been filed. MPEP 804 I-B states: “The “provisional” double patenting rejection should continue to be made by the examiner in each application as long as there are conflicting claims in more than one application unless that “provisional” double patenting rejection is the only rejection remaining in at least one of the applications.” In addition, as set forth above, the claims of the instant application are still obvious in view of the patented claims and Thanos. Therefore, the rejections above are maintained for the reasons of record.
Application No. 18/207,478
Claim 81-83, 85, and 91 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17, 19, 34, 37-39 of copending Application No. 18/207,478 (hereinafter Appl. 478, US 2024/0182580 A1, of record). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of Appl. 478 teach:
1. An antibody conjugate comprising an antibody that specifically binds to CD74 linked site-specifically to at least one payload moiety, wherein the antibody comprises a non-natural amino acid at a site selected from the group consisting of HC-F404, HC-K121, HC-Y180, HC-F241, HC-221, LC-T22, LC-S7, LC-N152, LC-K42, LC-E161, LC-D170, HC-S136, HC-S25, HC-A40, HC-S119, HC-S190, HC-K222, HC-R19, HC-Y52, or HC-S70, according to the Kabat, Chothia, or EU numbering scheme,….
2. The antibody conjugate of claim 1, wherein the non-natural amino acid is selected from the group consisting of …, p-azidomethyl-L-phenylalanine, …, and p-propargyloxy-phenylalanine. These read on instant claims 81-83.
19. The antibody conjugate of claim 1, wherein the antibody is an IgA, an IgD, an IgE, an IgG, or an IgM. This reads on claim 85.
37. A pharmaceutical composition comprising the antibody conjugate of claim 1 and a pharmaceutically acceptable carrier. This reads on claim 91.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 84, 86-90 and 92-100 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17, 19, 34, 37-39 of copending Application No. 18/207,478 (hereinafter Appl. 478, US 2024/0182580 A1, of record) as applied to claims 81-83, 85, and 91 above, and in view of Thanos (Thanos et al., US 2015/0017187 A1, Publication Date: 2015-01-15, cited in IDS of 10/26/2023, of record).
The claims of Appl. 478 teaches as set forth above. However, the claims of Appl. 478 do not explicitly teach, bispecific antibody, antibody fragment, pharmaceutical composition, polynucleotide, vector, host cells, or method of making the antibody with cell-free system.
Thanos teaches as set forth above.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to make an antibody conjugate as taught by the claims of Appl. 478, and based on the teachings from Thanos, one of ordinary skilled in the art would have known to make bispecific or scFv antibody-conjugate, polynucleotide, vector, host cells, or using a cell-free system to make the antibody as taught by Thanos, doing so would generate a multifunctional antibody which can have advantageous production yield, solubility, binding and/or activity, more than one payload molecule, as recognized by Thanos ([0008] and [0291]). One or ordinary skilled in the art would have had a reasonable expectation of success because Thanos teaches detailed methods of making antibodies with incorporated non-natural amino acids in both heavy chain and light chains (e.g. Examples 6, 17, 19, and [0527]).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
For this Double Patenting rejection, Applicant argues:
Applicant argues Applicant respectfully requests an abeyance for the rejection, until all other rejections have been overcome. At that time, Applicant will consider filing a Terminal Disclaimer over the' 478 application.
Applicant’s arguments have been fully considered but they are not persuasive because the claims of the instant application are still obvious in view of the co-pending claims and a terminal disclaimer has not been filed. MPEP 804 I-B states: “The “provisional” double patenting rejection should continue to be made by the examiner in each application as long as there are conflicting claims in more than one application unless that “provisional” double patenting rejection is the only rejection remaining in at least one of the applications.” Therefore, the rejections above are maintained for the reasons of record.
Application No. 18/203,348
Claim 81-83, 88 and 91 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-5, 7-9, 11, 13-19, 21-33, 43, 44, and 46-63 of copending Application No. 18/203,348 (hereinafter Appl. 348, US 2024/0139285 A1, of record). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of Appl. 348 teach:
1. An antibody conjugate comprising an antibody, or an antigen-binding fragment thereof, covalently linked to a drug payload and further covalently linked to an immunomodulatory payload, wherein the drug payload is a cytotoxic compound, wherein the immunomodulatory payload is an agonist of the STING (stimulator of interferon genes) pathway.
19. The antibody conjugate of claim 8 wherein the antibody, or an antigen-binding fragment thereof, comprises two or more non-natural amino acids suitable for conjugation, optionally wherein at least one of the two or more non-natural amino acids residues is a pAMF residue. As evidenced by the specification: “pAMF” mutation refers to a variant phenylalanine residue, i.e., para-azidomethyl-L-phenylalanine, added or substituted into a polypeptide ([0074]). Thus, these read on the instant claims 81-83.
46. A pharmaceutical composition comprising an antibody conjugate of claims 1, and a pharmaceutically acceptable carrier.
53. The antibody conjugate of claim 1, wherein the antibody or antigen-binding fragment thereof comprises at least one non-natural amino acid at position Y180, position F404, F241, or position K42 that is covalently linked to the immunomodulatory payload or to the drug payload. One of ordinary skilled in the art would quickly recognize that K42 represents an amino acid position corresponding to light chain K42 according to the Kabat or Chothia numbering scheme.
54. The antibody conjugate of claim 53, wherein the antibody or antigen- binding fragment thereof comprises a non-natural amino acid at Y180 and a non-natural amino acid at K42.
55. The antibody conjugate of claim 53, wherein the antibody or the antigen- binding fragment thereof comprises a non-natural amino acid at F404 and a non-natural amino acid at K42. Taken together, these read on the instant claims 81-83, 88 and 91.
56. The antibody conjugate of claim 53, wherein the antibody or the antigen- binding fragment thereof comprises a non-natural amino acid at Y180, a non-natural amino acid at F241, and a non-natural amino acid at K42.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 84-87, 89, 90 and 92-100 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 81-107 of copending Application No. 18/203,348 (hereinafter Appl. 348, US 2024/0139285 A1, of record) as applied to claims 81-83 and 91 above, and in view of Thanos (Thanos et al., US 2015/0017187 A1, Publication Date: 2015-01-15, cited in IDS of 10/26/2023, of record).
The claims of Appl. 348 teaches as set forth above. However, the claims of Appl. 348 do not explicitly teach, monoclonal antibody, bispecific antibody, aglycosylated antibodies, antibody fragment such as scFv, polynucleotide, vector, host cells, or method of making the antibody with cell-free system.
Thanos teaches as set forth above.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to make an antibody conjugate as taught by the claims of Appl. 348, and based on the teachings from Thanos, one of ordinary skilled in the art would have known to make monoclonal, bispecific, aglycosylated or scFv antibody-conjugate, polynucleotide, vector, host cells, or using a cell-free system to make the antibody as taught by Thanos, doing so would generate a multifunctional antibody which can have advantageous production yield, solubility, binding and/or activity, more than one payload molecule, as recognized by Thanos ([0008] and [0291]). One or ordinary skilled in the art would have had a reasonable expectation of success because Thanos teaches detailed methods of making antibodies with incorporated non-natural amino acids in both heavy chain and light chains (e.g. Examples 6, 17, 19, and [0527]).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
For this Double Patenting rejection, Applicant argues:
For claims 81-83, 88, and 91, applicant argues by citing MPEP § 804(I)(B)(1)(b)(i): “If a provisional nonstatutory double patenting rejection is the only rejection remaining in an application having the earlier patent term filing date, the examiner should withdraw the rejection in the application having the earlier patent term filing date and permit that application to issue as a patent, thereby converting the provisional nonstatutory double patenting rejection in the other application into a nonstatutory double patenting rejection upon issuance of the patent."
For claims 84-87, 89, 90, and 92-100, applicant argues that Thanos et al. does not remedy the deficiencies of the '348 application.
Applicant’s arguments have been fully considered but they are not persuasive because the claims of the instant application are still obvious in view of the co-pending claims and a terminal disclaimer has not been filed. MPEP 804 I-B states: “The “provisional” double patenting rejection should continue to be made by the examiner in each application as long as there are conflicting claims in more than one application unless that “provisional” double patenting rejection is the only rejection remaining in at least one of the applications.” However, in this case, there are other rejections remained for this application. In addition, as set forth above, the claims of the instant application are still obvious in view of the patented claims and Thanos. Therefore, the rejections above are maintained for the reasons of record.
Application No. 18/357,956
Claim 81-89, and 91 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 45-65 of copending Application No. 18/357,956 (hereinafter Appl. 956, of record). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of Appl. 956 teach:
45. An antibody conjugate comprising a payload moiety linked to an antibody, wherein the antibody comprises a light chain, wherein said light chain comprises a non-natural amino acid at position LC-K42 according to the Kabat or Chothia numbering scheme.
46. The antibody conjugate of claim 45, wherein the non-natural amino acid is selected from the group consisting of para-azidomethylphenylalanine, …, p-azidomethyl-L-phenylalanine, …, and p-propargyloxy-phenylalanine. Taken together, these read on instant claims 81-83.
55. The antibody conjugate of claim 45, wherein the antibody is a monoclonal antibody. This reads on instant claim 84.
56. The antibody conjugate of claim 45, wherein the antibody is an IgA, an IgD, an IgE, an IgG, or an IgM antibody. This reads on instant claim 85.
57. The antibody conjugate of claim 45, wherein the antibody is humanized or human. This reads on instant claim 86.
58. The antibody conjugate of claim 45, wherein the antibody is aglycosylated. This reads on instant claim 87.
59. The antibody conjugate of claim 45, wherein the antibody is an antibody fragment. This reads on instant claim 88.
60. The antibody conjugate of claim 59, wherein the antibody fragment is selected from an Fv fragment, a Fab fragment, a F(ab′)2 fragment, a Fab′ fragment, an scFv (sFv) fragment, and an scFv-Fc fragment. This reads on instant claim 89.
65. A pharmaceutical composition comprising the antibody conjugate of claim 45 and a pharmaceutically acceptable carrier. This reads on instant claim 91.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 90 and 92-100 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 45-65 of copending Application No. 18/357,956 (hereinafter Appl. 956, of record) as applied to claims 81-89 and 91 above, and in view of Thanos (Thanos et al., US 2015/0017187 A1, Publication Date: 2015-01-15, cited in IDS of 10/26/2023, of record).
The claims of Appl. 956 teaches as set forth above. However, the claims of Appl. 956 do not explicitly teach, bispecific antibody, polynucleotide, vector, host cells, or method of making the antibody with cell-free system.
Thanos teaches as set forth above.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to make an antibody conjugate as taught by the claims of Appl. 956, and based on the teachings from Thanos, one of ordinary skilled in the art would have known to make bispecific antibody-conjugate, polynucleotide, vector, host cells, or using a cell-free system to make the antibody as taught by Thanos, doing so would generate a multifunctional antibody which can have advantageous production yield, solubility, binding and/or activity, more than one payload molecule, as recognized by Thanos ([0008] and [0291]). One or ordinary skilled in the art would have had a reasonable expectation of success because Thanos teaches detailed methods of making antibodies with incorporated non-natural amino acids in both heavy chain and light chains (e.g. Examples 6, 17, 19, and [0527]).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
For this Double Patenting rejection, Applicant argues:
Applicant respectfully requests an abeyance for the rejection, until all other rejections have been overcome. At that time, Applicant will consider filing a Terminal Disclaimer over the '956 application.
Applicant’s arguments have been fully considered but they are not persuasive because the claims of the instant application are still obvious in view of the co-pending claims and a terminal disclaimer has not been filed. MPEP 804 I-B states: “The “provisional” double patenting rejection should continue to be made by the examiner in each application as long as there are conflicting claims in more than one application unless that “provisional” double patenting rejection is the only rejection remaining in at least one of the applications.” Therefore, the rejections above are maintained for the reasons of record.
Application No. 18/491,656
Claim 81-89 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 55, 60-62, 64, 65, 67-70, 72-83, 87, and 92 of copending Application No. 18/491,656 (hereinafter Appl. 656, US 2024/0148890 A1, of record). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of Appl. 656 teach:
1. A method of treating or palliating pediatric acute myeloid leukemia (AML) in a patient in need thereof, comprising administering to the patient an antibody conjugate comprising an antibody that specifically binds to folate receptor alpha (FOLR1) and is linked site-specifically to at least one payload moiety, in an amount effective to treat or palliate the pediatric AML in the patient.
55. The method of claim 1, wherein the antibody comprises one or more non-natural amino acids at sites selected from the group consisting of: HC F404, HC-K121, HC-Y180, HC-F241, HC-221, LC-T22, LC-S7, LC-N152, LC-K42, LC-E161, LC-D170, HC-S136, HC S25, HC-A40, HC-S119, HC-S190, HC-K222, HC-R19, HC-Y52, and HC-S70, according to the Kabat, Chothia, or EU numbering scheme.
62. The method of claim 55, wherein the one or more non-natural amino acids:
is selected from the group consisting of …, p-azido-methyl-L-phenylalanine, compound 56, p-acyl-L-phenylalanine, …, or is a residue of compound (30) or compound (56). Taken together, these teach the instant claims 81-83.
87. The method of claim 1, wherein the antibody is: a monoclonal antibody, an IgA, an IgD, an IgE, an IgG, or an IgM, humanized or human, aglycosylated, and/or
an antibody fragment. This reads on instant claims 84-88.
92. The method of claim 87, wherein the antibody fragment is selected from an Fv fragment, a Fab fragment, a F(ab′)2 fragment, a Fab′ fragment, an scFv (sFv) fragment, and an scFv-Fc fragment. This reads on instant claim 89.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 90-100 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 55, 60-62, 64, 65, 67-70, 72-83, 87, and 92 of copending Application No. 18/491,656 (hereinafter Appl. 656, US 2024/0148890 A1, of record) as applied to claims 81-89 above, and in view of Thanos (Thanos et al., US 2015/0017187 A1, Publication Date: 2015-01-15, cited in IDS of 10/26/2023, of record).
The claims of Appl. 656 teaches as set forth above. However, the claims of Appl. 656 do not explicitly teach, bispecific antibody, pharmaceutical composition, polynucleotide, vector, host cells, or method of making the antibody with cell-free system.
Thanos teaches as set forth above.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to make an antibody as taught by the claims of Appl. 656, and based on the teachings from Thanos, one of ordinary skilled in the art would have known to make bispecific antibody-conjugate, pharmaceutical composition, polynucleotide, vector, host cells, or using a cell-free system to make the antibody as taught by Thanos, doing so would generate a multifunctional antibody which can have advantageous production yield, solubility, binding and/or activity, more than one payload molecule, as recognized by Thanos ([0008] and [0291]). One or ordinary skilled in the art would have had a reasonable expectation of success because Thanos teaches detailed methods of making antibodies with incorporated non-natural amino acids in both heavy chain and light chains (e.g. Examples 6, 17, 19, and [0527]).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
For this Double Patenting rejection, Applicant argues:
For claims 81-89, applicant argues by citing MPEP § 804(I)(B)(1)(b)(i): “If a provisional nonstatutory double patenting rejection is the only rejection remaining in an application having the earlier patent term filing date, the examiner should withdraw the rejection in the application having the earlier patent term filing date and permit that application to issue as a patent, thereby converting the provisional nonstatutory double patenting rejection in the other application into a nonstatutory double patenting rejection upon issuance of the patent."
For claims 90-100, applicant argues that Thanos et al. does not remedy the deficiencies of the '656 application.
Applicant’s arguments have been fully considered but they are not persuasive because the claims of the instant application are still obvious in view of the co-pending claims and a terminal disclaimer has not been filed. MPEP 804 I-B states: “The “provisional” double patenting rejection should continue to be made by the examiner in each application as long as there are conflicting claims in more than one application unless that “provisional” double patenting rejection is the only rejection remaining in at least one of the applications.” However, in this case, there are other rejections remained for this application. In addition, as set forth above, the claims of the instant application are still obvious in view of the patented claims and Thanos. Therefore, the rejections above are maintained for the reasons of record.
Application No. 18/775,242
Claim 81-89 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 55-76 of copending Application No. 18/775,242 (hereinafter Appl. 242, of record). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of Appl. 242 teach:
55. A method of reducing cell proliferation involving the folate receptor alpha (FOLR1) by administering to the subject an effective amount of an antibody conjugate comprising an antibody, wherein the antibody comprises: …., linked site-specifically to at least one payload moiety by one or more non-natural amino acids.
64. The method of claim 55, wherein the antibody drug conjugate comprises a non- natural amino acid at least at one site selected from HC-F404, HC-Y180, HC-F404, and LC-K42.
65. The method of claim 55, wherein the non-natural amino acids are selected from the group consisting of para-azidomethylphenylalanine and p-azido-methyl-L-phenylalanine. Taken together, these read on instant claims 81-83.
70. The method of claim 55, wherein the antibody is a monoclonal antibody selected from the group consisting of: an IgA, an IgD, an IgE, an IgG, and an IgM. This reads on instant claims 84 and 85.
71. The method of claim 55, wherein the antibody is humanized or human. This reads on instant claim 86.
72. The method of claim 55, wherein the antibody is aglycosylated. This reads on instant claim 87.
73. The method of claim 55, wherein the antibody is an antibody fragment selected from the group consisting of: an Fv fragment, a Fab fragment, a F(ab’ )2 fragment, a Fab’ fragment, an scFv (sFv) fragment, and an scFv-Fc fragment. This reads on instant claims 88 and 89.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 90-100 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 55-76 of copending Application No. 18/775,242 (hereinafter Appl. 242, of record) as applied to claims 81-89 above, and in view of Thanos (Thanos et al., US 2015/0017187 A1, Publication Date: 2015-01-15, cited in IDS of 10/26/2023, of record).
The claims of Appl. 242 teaches as set forth above. However, the claims of Appl. 242 do not explicitly teach, bispecific antibody, pharmaceutical composition, polynucleotide, vector, host cells, or method of making the antibody with cell-free system.
Thanos teaches as set forth above.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to make an antibody as taught by the claims of Appl. 242, and based on the teachings from Thanos, one of ordinary skilled in the art would have known to make bispecific antibody-conjugate, pharmaceutical composition, polynucleotide, vector, host cells, or using a cell-free system to make the antibody as taught by Thanos, doing so would generate a multifunctional antibody which can have advantageous production yield, solubility, binding and/or activity, more than one payload molecule, as recognized by Thanos ([0008] and [0291]). One or ordinary skilled in the art would have had a reasonable expectation of success because Thanos teaches detailed methods of making antibodies with incorporated non-natural amino acids in both heavy chain and light chains (e.g. Examples 6, 17, 19, and [0527]).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
For this Double Patenting rejection, Applicant argues:
For claims 81-89, applicant argues by citing MPEP § 804(I)(B)(1)(b)(i): “If a provisional nonstatutory double patenting rejection is the only rejection remaining in an application having the earlier patent term filing date, the examiner should withdraw the rejection in the application having the earlier patent term filing date and permit that application to issue as a patent, thereby converting the provisional nonstatutory double patenting rejection in the other application into a nonstatutory double patenting rejection upon issuance of the patent."
For claims 90-100, applicant argues that Thanos et al. does not remedy the deficiencies of the '242 application.
Applicant’s arguments have been fully considered but they are not persuasive because the claims of the instant application are still obvious in view of the co-pending claims and a terminal disclaimer has not been filed. MPEP 804 I-B states: “The “provisional” double patenting rejection should continue to be made by the examiner in each application as long as there are conflicting claims in more than one application unless that “provisional” double patenting rejection is the only rejection remaining in at least one of the applications.” In addition, as set forth above, the claims of the instant application are still obvious in view of the patented claims and Thanos. Therefore, the rejections above are maintained for the reasons of record.
Application No. 18/824,772
Claim 81-89, and 91 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of copending Application No. 18/824,772 (hereinafter Appl. 772, of record). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of Appl. 772 teach:
1. An antibody conjugate comprising an antibody that specifically binds to receptor tyrosine kinase orphan receptor 1 (ROR1) linked site-specifically to at least one payload moiety, wherein the antibody comprises one or more non-natural amino acids and wherein the antibody comprises three heavy chain CDRs from a VH sequence selected from SEQ ID NOs:854-1020, or variants thereof, and three light chain CDRs from a VL sequence selected from SEQ ID NOs:1021-1026, or variants thereof.
2. The antibody conjugate of claim 1, wherein the one or more non-natural amino acids is at an antibody amino acid site other than the amino terminus of the antibody or at an antibody amino acid site other than the carboxy terminus of the antibody.
4. The antibody conjugate of claim 1, wherein the antibody comprises one or more non-natural amino acids at sites selected from the group consisting of: HC-F404, HC-Y180, HC-F241, and LC-K42, according to the Kabat or EU numbering scheme of Kabat.
7. The antibody conjugate of claim 1, wherein the one or more non-natural amino acids is p- azidomethylphenylalanine or p-azido-methyl-L-phenylalanine. Taken together, these read on instant claims 81-83.
22. The antibody conjugate of claim 1, wherein the antibody is a monoclonal antibody. This reads on instant claim 84.
23. The antibody conjugate of claim 1, wherein the antibody is an IgA, an IgD, an IgE, an IgG, or an IgM. This reads on instant claim 85.
24. The antibody conjugate of claim 1, wherein the antibody is humanized or human. This reads on instant claim 86.
25. The antibody conjugate of claim 1, wherein the antibody is aglycosylated. This reads on instant claim 87.
26. The antibody conjugate of claim 1, wherein the antibody is an antibody fragment. This reads on instant claim 88.
27. The antibody conjugate of claim 26, wherein the antibody fragment is selected from an Fv fragment, a Fab fragment, a F(ab')2 fragment, a Fab' fragment, an scFv (sFv) fragment, and an scFv-Fc fragment. This reads on instant claim 89.
28. A pharmaceutical composition comprising an antibody conjugate of claim 1 and a pharmaceutically acceptable carrier. This reads on instant claim 91.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 90, 92-100 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of copending Application No. 18/824,772 (hereinafter Appl. 772, of record) as applied to claims 81-89 and 91 above, and in view of Thanos (Thanos et al., US 2015/0017187 A1, Publication Date: 2015-01-15, cited in IDS of 10/26/2023, of record).
The claims of Appl. 772 teaches as set forth above. However, the claims of Appl. 772 do not explicitly teach, bispecific antibody, polynucleotide, vector, host cells, or method of making the antibody with cell-free system.
Thanos teaches as set forth above.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to make an antibody conjugate as taught by the claims of Appl. 772, and based on the teachings from Thanos, one of ordinary skilled in the art would have known to make bispecific antibody-conjugate, polynucleotide, vector, host cells, or using a cell-free system to make the antibody as taught by Thanos, doing so would generate a multifunctional antibody which can have advantageous production yield, solubility, binding and/or activity, more than one payload molecule, as recognized by Thanos ([0008] and [0291]). One or ordinary skilled in the art would have had a reasonable expectation of success because Thanos teaches detailed methods of making antibodies with incorporated non-natural amino acids in both heavy chain and light chains (e.g. Examples 6, 17, 19, and [0527]).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
For this Double Patenting rejection, Applicant argues:
For claims 81-89, and 91 applicant argues by citing MPEP § 804(I)(B)(1)(b)(i): “If a provisional nonstatutory double patenting rejection is the only rejection remaining in an application having the earlier patent term filing date, the examiner should withdraw the rejection in the application having the earlier patent term filing date and permit that application to issue as a patent, thereby converting the provisional nonstatutory double patenting rejection in the other application into a nonstatutory double patenting rejection upon issuance of the patent."
For claims 90, and 92-100, applicant argues that Thanos et al. does not remedy the deficiencies of the '772 application.
Applicant’s arguments have been fully considered but they are not persuasive because the claims of the instant application are still obvious in view of the co-pending claims and a terminal disclaimer has not been filed. MPEP 804 I-B states: “The “provisional” double patenting rejection should continue to be made by the examiner in each application as long as there are conflicting claims in more than one application unless that “provisional” double patenting rejection is the only rejection remaining in at least one of the applications.” In addition, as set forth above, the claims of the instant application are still obvious in view of the patented claims and Thanos. Therefore, the rejections above are maintained for the reasons of record.
U.S. Patent No. 9,764,039
Claims 81-100 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-36 of U.S. Patent No. 9,764,039 (hereinafter, Pat. 039, corresponding Appl. No. 14/328,532), in view of Thanos (Thanos et al., US 2015/0017187 A1, Publication Date: 2015-01-15, cited in IDS of 10/26/2023, of record). It is noted that Thanos et al., US 2015/0017187 A1 is also corresponding to Appl. 14/328,532, thus, Pat. 039 and Thanos share the same disclosure.
The claims of Pat. 039 teach:
1. An antibody of the IgG class comprising six or fewer site-specific non-natural amino acid residues, wherein at least one of said site-specific non-natural amino acid residues comprises an azide moiety and at least one of said site-specific non-natural amino acid residues comprises a tetrazine moiety, wherein at least one of the said site-specific non-natural amino acid residues comprising the azide moiety or the tetrazine moiety is at heavy chain site 404 according to the EU index of Kabat.
3. The antibody of claim 1, wherein at least one site-specific non-natural amino acid is in a light chain or light chain variable domain.
9. The antibody of claim 1, wherein at least one of said site-specific non-natural amino acid residue is at one or more sequence positions selected from the group consisting of light chain residues 7 and 22 according to the Kabat numbering scheme, light chain residue 152 according to the EU index of Kabat, heavy chain residues 19, 25, 40, 52, 70, and 110 according to the Kabat numbering scheme, and heavy chain residues 119, 121, 136, 180, 190, 221, and 222 according to the EU index of Kabat.
13. The antibody of claim 1, that is of a class or subclass selected from the group consisting of IgG1, IgG2, IgG3 and IgG4.
14. The antibody of claim 9, wherein each further site-specific non-natural amino acid residue comprises a moiety selected from the group consisting of amino, carboxy, acetyl, hydrazino, hydrazido, semicarbazido, sulfanyl, and alkynyl, wherein said site-specific non-natural amino acid residue is not one of the 20 amino acids or pyrrolysine or selenocysteine, or post-translationally modified variant thereof.
35. The antibody of claim 1, wherein at least one of the two or more site-specific non-natural amino acid residues is p-azido-L-phenylalanine.
36. The antibody of claim 1, wherein at least one of the two or more site-specific non-natural amino acid residues is p-azidomethyl-L-phenylalanine.
The claims of Pat. 039 teach as set forth above. However, the claims of Pat. 039 do explicitly teach position K42 of light chain, bispecific antibody, polynucleotide, vector, host cells, or method of making the antibody with cell-free system.
Thanos teaches as set forth above.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to make antibody with one or more non-natural amino acid substitution as light chain of an antibody as taught by the claims of Pat. 039, and try different amino acid at the framework region of the light chain, such as K42, because Thanos teaches: 1) any position in light chain can be substituted with a non-natural amino acid; 2) lysine can be replaced by a non-natural amino acid such as K-AEK in framework region of light chain. One of ordinary skill in the art would understand that incorporation of non-natural amino acid in the framework region would unlikely change the binding properties of the antibody, as recognized by applicant (see paragraph 4 on page 5 of the Remarks filed on 02/18/2025). The motivation would have been to expand the options of antibodies and to develop a potential better antibody for production yield, solubility, binding and/or activity. Given the limited number of amino acids in the framework region of a light chain, one or ordinary skilled in the art would have had a reasonable expectation of success to reach the claimed antibody because Thanos teaches detailed methods of making antibodies with incorporated non-natural amino acids in both heavy chain and light chains (e.g. Examples 6, 17, 19, and [0527]).
Regarding claim 84, Thanos teaches monoclonal antibody, such as Trastuzumab (Table 10, on page 82).
Regarding claim 85, Thanos teaches that the antibody of any of the preceding claims that is of a class or subclass selected from the group consisting of IgA, IgA, IgA2, IgD, IgE, IgG, IgGl, IgG2, IgG3 and IgM (claim 16).
Regarding claim 86, Thanos teaches that the antibody can be a humanized antibody ([0429]).
Regarding claim 87, Thanos teaches the non-natural amino acid incorporation into an aglycosylated antibody (Example 9).
Regarding claim 88, 89, Thanos teaches antibody fragments, e.g. Fv, Fc, Fab, scFv (claim 17).
Regarding claim 90, Thanos teaches the method can be applied to bispecific antibodies ([0429] and [0430]).
Regarding claim 91, Thanos teaches pharmaceutical composition comprising the claimed antibody and a pharmaceutically acceptable carrier ([0432], [0433]).
Regarding claim 92-94, Thanos teaches polynucleotide coding antibody and expression vector comprising the DNA and routine antibody production methods ([453], [454], and [0525]).
Regarding claim 95, Thanos teaches methods of making antibodies with non-natural amino acid incorporation in heavy chain, light chain or both (Examples 1-3, 6, 8).
Regarding claim 96 and 97, Thanos teaches methods of incorporation of para-azido-methyl phenylalanine and para-azido phenylalanine in antibodies (Examples 6, 17, 19, and [0527]).
Regarding claim 98 and 99, Thanos teaches that both heavy chain and the light chain were synthesized by cell-free protein synthesis, from an E.coli strain ([0556], Example 17).
Regarding claim 100, Thanos teaches isolated antibody preparations have less than about 5%, less than about 4%, less than about 3%, less than about 2% or less than about 1% of contaminating proteins by weight ([0037]).
Response to Arguments
For this Double Patenting rejection, Applicant argues:
The instant claims recite an antibody with a substitution at an amino acid position
corresponding to K42 according to the Kabat or Chothia numbering scheme. None of the claims in the '039 patent recites an antibody with a K42 substitution. Therefore, Applicant submits that the instant claims are patentably distinct over the '039 patent.
Additionally, the '039 patent specification does not disclose any data that would motivate a person of skill to create an antibody with a K42 substitution. This is because the specification postulates substitutions at over 100 positions, but provides no data for a K42 substitution. See published specification of the '039 patent (US 2015/0017187) at paragraphs [0113]-[0115].
Applicant’s arguments have been fully considered but they are not persuasive. First, although the claims of Pat. 039 do not cite K42 substitution, the scope of claim 1 of Pat. 039 (comprising six or fewer site-specific non-natural amino acid residues) would encompass the K42 substitution. Thus, the scope of the instant claims overlaps with the scope of the claims of Pat. 039. In addition, as set forth above, the claims of the instant application are still obvious in view of the patented claims and Thanos. Therefore, the rejections above are maintained for the reasons of record.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/CHENG LU/ Examiner, Art Unit 1642
/PETER J REDDIG/ Primary Examiner, Art Unit 1646