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
Status of the Claims
1. Claims 1-25 are the original claims filed 9/30/2022. In the Preliminary Amendment of 1/12/2023, claims 3-20, 22 and 24 are amended and claim 25 is canceled. In the Response of 2/9/2026, Claims 1, 7, 9-17 and 19 are amended and Claims 2 and 8 are canceled.
Claims 1, 3-7 and 9-24 are all the claims.
The amendment of the claims raises new grounds for rejection. The Office Action is final.
Priority
2. USAN 17/937,440, filed 09/30/2022, is a Continuation of PCT/EP2021/058439, filed 03/31/2021, claims foreign priority to EP 20167624.4, filed 04/01/2020.
Information Disclosure Statement
3. As of 3/27/2026, a total of two (2) IDS are filed: 1/23/2023; and 6/6/2025. The corresponding initialed and dated 1449 form is considered and of record.
Withdrawal of Objections
Specification
4. The objection to the disclosure because of informalities is withdrawn. Both clean and marked-up copies of the specification are filed.
a) The objection to the figure legends for Figures 14 and 19-24 is withdrawn in view of the substitute specification filed 1/12/2023.
b) The specification is amended to rectify the improper use of the term, i.e., UniProt, NCBI, ATCC, NucLight, AffiniPure, FACS, BioGlo, OneGlo, GlutaMAx, BD FACSAria, Eppendorf, Lipofectamine, Biacore, TSKgel, Superdex, LabChip, Amicon, MabSelectSure, X-Vivo, Bio-plex, iQue, ForeCyte, Sepharose, eFluor, Aim V, Histopaque, GingisKHAN, UNIX, DNASTAR, megalign, which is a trade name or a mark used in commerce.
Claim Objections
5. The objection to Claims 1-24 because of informalities is moot for the canceled claims and withdrawn for the pending claims.
A. Claim 1 is amended to recite reduced or no reactivity towards pre-existing anti-drug antibodies in comparison to the same bispecific molecule whose C-terminus of the CH1 domain terminates with EPKSC (SEQ ID NO:6)".
B. Claims 7 and 10 are amended to recite “of claim 1,” to comport with the other dependent claims.
Withdrawal of Rejections
Claim Rejections - 35 USC § 112(b)
6. The rejection of Claims 1-24 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is moot for the canceled claims and withdrawn for the pending claims.
A. Claims 1-24 are amended to replace the phrase “capable of” with “that binds.”
B. Claim 10 is amended to set forth the features required to qualify the bispecific antigen binding molecule being trivalent.
C. Claim 11 is amended to depend from claim 9.
D. Claim 12 is amended to depend from claim 9.
E. Claim 13 is amended to depend from claim 9.
F. Claim 14 is amended to depend from claim 9.
G. Claim 15 is amended to depend from claim 13.
H. Claim 15 (c) is amended to replace “three light chains” with “four light chains” and to depend from claim 13.
I. Claim 16 is amended to recite “an
J. Claims 17 and 19-20 are amended to delete the parentheses but not the enclosed text therein in the claims.
Claim Rejections - 35 USC § 112(d)
7. The rejection of Claims 8, 11, 12, and 15 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form is moot for the canceled claims and withdrawn for the pending claims.
A. Claim 8 is canceled.
B. Claim 11 is amended to depend from claim 9.
C. Claim 12 is amended to depend from claim 9.
D. Claim 15 is amended to depend from claim 9.
Claim Rejections - 35 USC § 112(a)
Written Description
8. The rejection of Claims 1-24 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is moot for the canceled claims and withdrawn for the pending claims.
Claims are amended to clarify structure insofar as the first-, second- and third- (cross-fab fragment) Fab fragments vis-à-vis the Fc domain of dual subunit stabilization and comprising for the third- (cross-fab fragment) Fab fragment the3 CH1 domain terminating with the sequence od SEQ ID NO: 1, 2 and/or 3.
Claims are amended to clarify the function insofar as the corresponding first and second antigen binding and having reduced or no reactivity towards pre-existing anti-drug antibodies compared to the same bispecific molecule comprising a CH1 terminus with the amino acid sequence of SEQ ID NO: 6.
Rejections Maintained
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.
9. The rejection of Claims
a) Applicants allege Claim 1 is amended herein to recite the "bispecific antigen binding molecule has reduced or no reactivity towards pre-existing anti-drug antibodies in comparison to the same bispecific molecule in which the C-terminal end of the CH1 domain terminates with the amino acid sequence EPKSC (SEQ ID NO:6)". Amann in no way teaches or suggests that an antibody comprising SEQ ID NO: 217 would have "reduced or no reactivity towards pre-existing anti-drug antibodies in comparison to the same bispecific molecule in which the C-terminal end of the CH1 domain terminates with the amino acid sequence EPKSC".
Response to Arguments
Amann teaches a bispecific antigen binding molecule in Figure 12A for a CROSS-FAB- comprising bispecific molecule comprising elements (a)-(c) of the instant claim 1:
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Ref Fab anti-OX40 (first arm) corresponds to element (a) of instant claim 1; Ref Fab anti-OX40 (second arm) corresponds to element (b) of instant claim 1; and Ref cross-fab anti-FAP (HV-CL/VH-CH1; first or second arms) correspond to element (c) of instant claim 1. The POSA would recognize the second arm of the Ref cross-fab anti-FAP corresponding to a fourth Fab fragment.
Amann teaches the CH1 domain of the cross-fab fragment terminates with amino acid sequence EPKSCD (VLCH1 of SEQ ID NO: 217) that provides the sequence of the VL-CH1 light chain of the anti-FAP cross-Fab. Amann teaches bispecific antibodies comprising the sequence of SEQ ID NO: 217 as follows:
(195) In a particular aspect, the invention provides a bispecific antigen binding molecule comprising (a) a first heavy chain comprising the amino acid sequence of SEQ ID NO:303, a first light chain comprising the amino acid sequence of SEQ ID NO:182, a second heavy chain comprising the amino acid sequence of SEQ ID NO:229, and a second light chain comprising the amino acid sequence of SEQ ID NO:217, or (b) a first heavy chain comprising the amino acid sequence of SEQ ID NO:231, a first light chain comprising the amino acid sequence of SEQ ID NO: 186, a second heavy chain comprising the amino acid sequence of SEQ ID NO:229, and a second light chain comprising the amino acid sequence of SEQ ID NO:217, or (c) a first heavy chain comprising the amino acid sequence of SEQ ID NO:233, a first light chain comprising the amino acid sequence of SEQ ID NO:190, a second heavy chain comprising the amino acid sequence of SEQ ID NO:229, and a second light chain comprising the amino acid sequence of SEQ ID NO:217, or (d) a first heavy chain comprising the amino acid sequence of SEQ ID NO:235, a first light chain comprising the amino acid sequence of SEQ ID NO:194, a second heavy chain comprising the amino acid sequence of SEQ ID NO:229, and a second light chain comprising the amino acid sequence of SEQ ID NO:217, or (e) a first heavy chain comprising the amino acid sequence of SEQ ID NO: 237, a first light chain comprising the amino acid sequence of SEQ ID NO:198, a second heavy chain comprising the amino acid sequence of SEQ ID NO:229, and a second light chain comprising the amino acid sequence of SEQ ID NO:217, or (f) a first heavy chain comprising the amino acid sequence of SEQ ID NO:239, a first light chain comprising the amino acid sequence of SEQ ID NO:202, a second heavy chain comprising the amino acid sequence of SEQ ID NO:229, and a second light chain comprising the amino acid sequence of SEQ ID NO:217.
The POSA recognizes that a control antibody comprising a native CH1 domain comprises the C-terminal sequence of EPKSC (SEQ ID NO: 6) as instantly claimed. (Akiba et al (Sci Rep 2021 Sep 30;11:19411; PTO 892). EPKSC represents the natural, normal C-terminus of a human IgG1 CH1 domain, immediately preceding the hinge region.
In response to applicants’ argument “Amann in no way teaches or suggests that an antibody comprising SEQ ID NO: 217 would have "reduced or no reactivity towards pre-existing anti-drug antibodies in comparison to the same bispecific molecule in which the C-terminal end of the CH1 domain terminates with the amino acid sequence EPKSC", applicant is reminded that the reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006) (motivation question arises in the context of the general problem confronting the inventor rather than the specific problem solved by the invention); Cross Med. Prods., Inc. v. Medtronic Sofamor Danek, Inc., 424 F.3d 1293, 1323, 76 USPQ2d 1662, 1685 (Fed. Cir. 2005).
b) Applicants allege Amann teaches formats designed to prevent triggering of anti-drug antibodies to the construct (We transferred the clone 20G2 to moIgG to prevent triggering of anti-drug-antibodies (ADAs) in immune competent mice)". So Amann discloses making an antibody more mouse-like when the antibody is to be used in mice; this would suggest, at most, to a person of ordinary skill in the art that, if an antibody is to be used in a human, it should be made to look more human (e.g., at least a chimeric antibody, or more preferably fully human antibody). This is not a teaching or suggestion of modification of the C-terminal end of a CH1 domain in a crossmab Fab to reduce reactivity to anti-drug antibodies.
Response to Arguments
Most notably, none of the instant claims are drawn to the use or administration of the bispecific antigen binding molecule applicable to humans. Even assuming, arguendo, any construct of Amann is construed for human use, the disclosure is specifically dispositive, and encompasses mice or rodents.
(137) An “individual” or “subject” is a mammal. Mammals include, but are not limited to, domesticated animals (e.g. cows, sheep, cats, dogs, and horses), primates (e.g. humans and non-human primates such as monkeys), rabbits, and rodents (e.g. mice and rats). Particularly, the individual or subject is a human.
The benefit(s) of replacing a CH1 EPKSC with EPKSCD towards reduced or no reactivity towards pre-existing anti-drug antibodies would have been a consequence of following the suggestions of the prior art as discussed above. “The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious.” Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). Mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. In re Wiseman, 596 F.2d 1019, 201 USPQ 658 (CCPA 1979) (Claims were directed to grooved carbon disc brakes wherein the grooves were provided to vent steam or vapor during a braking action. A prior art reference taught noncarbon disc brakes which were grooved for the purpose of cooling the faces of the braking members and eliminating dust. The court held the prior art references when combined would overcome the problems of dust and overheating solved by the prior art and would inherently overcome the steam or vapor cause of the problem relied upon for patentability by applicants. Granting a patent on the discovery of an unknown but inherent function (here venting steam or vapor) “would remove from the public that which is in the public domain by virtue of its inclusion in, or obviousness from, the prior art.” 596 F.2d at 1022, 201 USPQ at 661.).
The rejection is maintained.
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.
10. The rejection of Claims 1-12 and 16-24 on the ground of nonstatutory double patenting as being unpatentable over claims 10-14 of U.S. Patent No. 11780919 is moot for the canceled claims and maintained for the pending claims.
Applicants allege claims 10-14 of U.S. Patent No. 11,780,919 because claims 10-14 do not recite, teach or suggest "cross-Fab comprises a VL-CH1 with a C terminal
CH1 connector of SEQ ID NO: EPKSCD and EPKSCS" as stated in the Office Action. Claims 10-14 recite no sequences, and claim 1 (from which claims 10-14 depend) recite only CDR sequences. As such, a person of ordinary skill in the art would not be motivated to modify claims 10-14 of U.S. Patent No. 11,780,919 to produce the claims to the presently-claimed antibodies.
Response to Arguments
The reference claims as follows teach a cross-fab for a bispecific antibody that is “fused” to one of the subunits of the Fc region:
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‘919 teaches the meaning of “fused” with respect to the cross-fab for a bispecific antibody in addition to the native segment (SEQ ID NO: 163) and variant (SEQ ID NO: 164 and 165) as follows:
(83) The term “CH1 domain” denotes the part of an antibody heavy chain polypeptide that extends approximately from EU position 118 to EU position 215 (EU numbering system according to Kabat). In one aspect, a CH1 domain has the amino acid sequence of ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKKV (SEQ ID NO:166). Usually, a segment having the amino acid sequence of EPKSC (SEQ ID NO:163) is following to link the CH1 domain to the hinge region. The inventors found that a CH1 domain that is not fused to a hinge region may lead to reactivity with pre-existing antibodies (ADAs) in the human body which are not present if a variant EPKSCD (SEQ ID NO:164) or EPKSCS (SEQ ID NO:165) is present. A CH1 domain with a free C-terminal end can be found for instance in a crossfab fragment.
MPEP 804(II)(B)(1) stating in part:
The specification can be used as a dictionary to learn the meaning of a term in the claim. Toro Co. v. White Consol. Indus., Inc., 199 F.3d 1295, 1299, 53 USPQ2d 1065, 1067 (Fed. Cir. 1999) (“[W]ords in patent claims are given their ordinary meaning in the usage of the field of the invention, unless the text of the patent makes clear that a word was used with a special meaning.”); Renishaw PLC v. Marposs Societa' per Azioni, 158 F.3d 1243, 1250, 48 USPQ2d 1117, 1122 (Fed. Cir. 1998) (“Where there are several common meanings for a claim term, the patent disclosure serves to point away from the improper meanings and toward the proper meanings.”). “The Patent and Trademark Office (‘PTO’) determines the scope of the claims in patent applications not solely on the basis of the claim language, but upon giving claims their broadest reasonable construction ‘in light of the specification as it would be interpreted by one of ordinary skill in the art.’ ” Phillips v. AWH Corp., 415 F.3d 1303, 1316, 75 USPQ2d 1321, 1329 (Fed. Cir. 2005) (en banc) (quoting In re Am. Acad. of Sci. Tech. Ctr., 367 F.3d 1359, 1364, 70 USPQ2d 1827, 1830 (Fed. Cir. 2004); see also MPEP § 2111.01.
The rejection is maintained.
11. The provisional rejection of Claims 1-24 on the ground of nonstatutory double patenting as being unpatentable over claims 13-23 of copending Application No. 18/457,729 (reference application US 20240117049) is moot for the canceled claims and maintained for the pending clams.
Applicants allege claims 1, 3-7, and 9-24 are not obvious over claims 1-28 of U.S. Patent Application No. 18/457,729 because claims 1-28 do not recite, teach or suggest "cross-Fab comprises a VL-CH1 with a C terminal CH1 connector of SEQ ID NO: EPKSCD and EPKSCS" as stated in the Office Action. None of the sequences recited in claims comprise the amino acid sequences EPKSCD or EPKSCS. As such, a person of ordinary skill in the art would not be motivated to modify the claims of U.S. Patent Application No. 18/457,729 to produce the claims to the presently-claimed antibodies.
Response to Arguments
The reference claims as follows teach a cross-fab for a bispecific antibody that is “fused” to one of the subunits of the Fc region:
13. (Currently amended) The bispecific antigen binding molecule of claim 1, wherein the bispecific antigen binding molecule comprises (a) at least two Fab fragments capable of specific binding to OX40 each connected to the N-terminus of one of subunits of the Fc region, and(b) one cross-Fab fragment capable of specific binding to FAP fused to the C-terminus of one of subunits of the Fc region, and (c) the Fc region composed of a first and a second subunit capable of stable association.
14. (Original) The bispecific antigen binding molecule of claim 13, wherein the VH-C kappa chain of the cross-fab fragment capable of specific binding to FAP is fused to the C- terminus of one of subunits of the Fc region.
15. (Currently amended) The bispecific antigen binding molecule of claim 1, consisting of (aa) a first Fab fragment capable of specific binding to OX40,(ab) a second Fab fragment capable of specific binding to OX40, (b) a cross-Fab fragment capable of specific binding to FAP fused to the C-terminus of one of subunits of the Fc region, and (c) the Fc region composed of a first and a second subunit capable of stable association, wherein the first Fab fragment (aa) is fused at the C-terminus of the VH-CH1 chain to the N terminus of the first subunit and the second Fab fragment (ab) is fused at the C- terminus of the VH-CH1 chain to the N-terminus of the second subunit.
16. (Currently amended) The bispecific antigen binding molecule of claim 1, consisting of (aa) a first Fab fragment capable of specific binding to OX40,(ab) a second Fab fragment capable of specific binding to OX40,(ac) a third Fab fragment capable of specific binding to OX40, (b) a cross-Fab fragment capable of specific binding to FAP fused to the C-terminus of one of subunits of the Fc region, and (c) the Fc region composed of a first and a second subunit capable of stable association, wherein the second Fab fragment (ab) is fused at the C-terminus of the VH-CH1 chain to the N-terminus of the VH-CH1 chain of the first Fab fragment (aa), which is in turn fused at its C-terminus to the N-terminus of the first subunit, and the third Fab fragment (ac) is fused at the C-terminus of the Fab heavy chain to the N-terminus of the second subunit.
17. (Currently amended) The bispecific antigen binding molecule of claim 1, consisting of (aa) a first Fab fragment capable of specific binding to OX40,(ab) a second Fab fragment capable of specific binding to OX40, (ac) a third Fab fragment capable of specific binding to OX40, (ad) a fourth Fab fragment capable of specific binding to OX40, (b) a cross-Fab fragment capable of specific binding to FAP fused to the C-terminus of one of subunits of the Fc region, and (c) the Fc region composed of a first and a second subunit capable of stable association, wherein the second Fab fragment (ab) is fused at the C-terminus of the VH-CH1 chain to the N terminus of the VH-CH1 chain of the first Fab fragment (aa), which is in turn fused at its C terminus to the N-terminus of the first subunit, and the fourth Fab fragment (ad) is fused at the C terminus of the VH-CH1 chain to the N-terminus of the VH-CH1 chain of the third Fab fragment (ac), which is in turn fused at its C-terminus to the N-terminus of the second subunit.
18. (Currently amended) An isolated nucleic acid encoding the bispecific antigen binding molecule of claim 1.
19. (Original) An expression vector comprising the isolated nucleic acid of claim 18.
20. (Original) A host cell comprising isolated nucleic acid of claim 18 or the expression vector of claim 19.
21. (Original) A method of producing a bispecific antigen binding molecule, comprising culturing the host cell of claim 20 under conditions suitable for the expression of the bispecific antigen binding molecule, and isolating the bispecific antigen binding molecule.
22. (Currently amended) A pharmaceutical composition comprising the bispecific antigen binding molecule of any one of claims 1 to 17claim 1 and a pharmaceutically acceptable carrier.
23. (Original) The pharmaceutical composition of claim 22, further comprising an additional therapeutic agent.
‘729 teaches the meaning of “fused” with respect to the cross-fab for a bispecific antibody in addition to the native segment (SEQ ID NO: 163) and variant (SEQ ID NO: 164 and 165) as follows:
[0169] The term “CH1 domain” denotes the part of an antibody heavy chain polypeptide that extends approximately from EU position 118 to EU position 215 (EU numbering system according to Kabat). In one aspect, a CH1 domain has the amino acid sequence of ASTKGPSVFP LAPSSKSTSG GTAALGCLVK DYFPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKKV (SEQ ID NO: 166). Usually, a segment having the amino acid sequence of EPKSC (SEQ ID NO:163) is following to link the CH1 domain to the hinge region. The inventors found that a CH1 domain that is not fused to a hinge region may lead to reactivity with pre-existing antibodies (ADAs) in the human body which are not present if a variant EPKSCD (SEQ ID NO:164) or EPKSCS (SEQ ID NO: 165) is present. A CH1 domain with a free C-terminal end can be found for instance in a crossfab fragment.
MPEP 804(II)(B)(1) stating in part:
The specification can be used as a dictionary to learn the meaning of a term in the claim. Toro Co. v. White Consol. Indus., Inc., 199 F.3d 1295, 1299, 53 USPQ2d 1065, 1067 (Fed. Cir. 1999) (“[W]ords in patent claims are given their ordinary meaning in the usage of the field of the invention, unless the text of the patent makes clear that a word was used with a special meaning.”); Renishaw PLC v. Marposs Societa' per Azioni, 158 F.3d 1243, 1250, 48 USPQ2d 1117, 1122 (Fed. Cir. 1998) (“Where there are several common meanings for a claim term, the patent disclosure serves to point away from the improper meanings and toward the proper meanings.”). “The Patent and Trademark Office (‘PTO’) determines the scope of the claims in patent applications not solely on the basis of the claim language, but upon giving claims their broadest reasonable construction ‘in light of the specification as it would be interpreted by one of ordinary skill in the art.’ ” Phillips v. AWH Corp., 415 F.3d 1303, 1316, 75 USPQ2d 1321, 1329 (Fed. Cir. 2005) (en banc) (quoting In re Am. Acad. of Sci. Tech. Ctr., 367 F.3d 1359, 1364, 70 USPQ2d 1827, 1830 (Fed. Cir. 2004); see also MPEP § 2111.01.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
New Grounds for Objection
Claim Objections
12. Claim 23 is objected to because of the following informalities:
a) Amend Claim 23 to delete “suitable” to remove the language from conditional language to a positive language.
Appropriate correction is required.
New Grounds for Rejection
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.
13. Claims 1, 3-7 and 9-24 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
a) Claims 1, 3-7 and 9-24 are indefinite for the newly added “wherein” clause in claim 1. The claims do not distinguish which of the C-terminus for the CH1 domains of the first, second and/or third Fab fragments of the same antibody (control) comprise the amino acid sequence EPKSC (SEQ ID NO: 6). The “wherein” clause recites “the CH1 domain” as a singular form.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
14. Claim 5 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 5 fails to further limit the subject matter of the claim upon which it depends. Claim 5 recites “The bispecific antigen binding molecule of claim 1, wherein the CH1 domain of the crossfab fragment terminates with the amino acid sequence selected from the group consisting of EPKSCD (SEQ ID NO:3), EPKSCDK (SEQ ID NO:4) and EPKSCDKTHL (SEQ ID NO:5).”
Claim 1 is amended to delete “EPKSCDK (SEQ ID NO:4) and EPKSCDKTHL (SEQ ID NO:5).”
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Conclusion
12. No claims are allowed.
13. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNN A. BRISTOL whose telephone number is (571)272-6883. The examiner can normally be reached Mon-Fri 9 AM-5 PM.
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, Wu Julie can be reached at 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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LYNN ANNE BRISTOL
Primary Examiner
Art Unit 1643
/LYNN A BRISTOL/ Primary Examiner, Art Unit 1643
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