DETAILED ACTION
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 .
Election/Restrictions
1. The Election filed 5/20/2026, in response to the Office Action of 4/2/2026, is acknowledged and has been entered. Applicants elected without traverse the species of an anti-LAG-3 antibody or antigen-binding portion comprising the H-CDR1-3 and L-CDR1-3 amino acid sequences of SEQ ID NOs: 41, 42, 43, 44, 45, and 40; the heavy chain variable domain of SEQ ID NO:7 and 30, the light chain variable domain of SEQ ID NO:8 and 34; and the binding epitope having amino acid residues H85, P86, A87, P89, S91, W92, and G93 of SEQ ID NO: 68. Claims 41-61 are pending. Claims 41-61 are currently under prosecution as drawn to the elected species.
Priority
2. Application is a Continuation of application 17/834,497 (Issued patent No. 11834503) filed on 6/7/2022 which is a divisional application of 16/340,855 (issued patent No.11390676) filed on 4/10/2019 which claims the benefit and priority of PCT/EP2017/076188 filed on 10/13/2017 which claims the benefit and priority of provisional application 62/407,678 filed on 10/13/2016. Application has been reviewed and priority has been granted to 62/407,678 and the effective filing date of 10/13/2016.
Specification
3. The specification is objected for containing the following sequence listings of SEQ ID NOs: 39, 45, 47, 60, and 66. The listed sequences all contained <4 amino acids and were changed to the dummy sequence “000.” Please amend the specification to remove the “SEQ ID NO:XX” and replace with the actual amino acid sequence listing. Below are the places in the specification listing the SEQ ID NOs from above:
Page 4 [0025]: ALL
Page 5 [0030]: ALL
Page 22 [0095]: ALL
Page 80 Table 9: ALL
Page 81 Table 10: ALL
Page 87: SEQ ID NOs: 39, 45, 47
Page 88: SEQ ID NOs:60, 66
Claim Objections
4. Claim 41 is objected based on the listing of SEQ ID NOs: 39, 45, 47, 60, and 66. The sequence listings all contain <4 amino acids and were changed to dummy sequence “000.” Please amend claim 41 to remove reference to the SEQ ID NOs listed above and replace with the exact amino acid sequences.
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.
5. Claims 41-61 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.
Claim 41 recites the limitation "the H-CDR1-3 and L-CDR1-3 amino acid sequences of" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 42 recites the limitation "the heavy chain variable domain…..and the light chain variable domain" in lines 2-3. There is insufficient antecedent basis for this limitation in the claim.
Claim 50 recites “An anti-LAG-3 antibody or an antigen-binding portion thereof, wherein said antibody competes for binding to human LAG-3 with the anti-LAG-3 antibody or antigen-binding portion thereof according to claim 41.” The claim references multiple anti-LAG-3 antibodies and portions thereof, and it is unclear if the claim is referencing different or the same antibodies and portions thereof. Additionally, it is unclear if the antigen-binding portion thereof is encompassed by “said antibody” that competes or binding to LAG-3.
Claims 52 and 54 recites the limitation "the heavy chain sequence" and “the light chain sequence” in lines 1-2. There is insufficient antecedent basis for this limitation in the claim. Both claims depend from claim 41 which recites H-CDR1-3 and L-CDR1-3 sequences, claim 42 recites “the heavy chain variable domains” and “the light chain variable domains,” and claim 49 recites “an HC” and “an LC.” It is unclear what heavy and light chain sequences are being referred to. For the sake of compact prosecution, examiner will interpret it as being the H-CDR1-3 and L-CDR1-3 sequences claimed in claim 41.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
6. Claim 50 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a WRITTEN DESCRIPTION rejection.
Claim 50 recites an anti-LAG-3 antibody or an antigen-binding portion thereof, wherein said antibody functions to compete for binding to human LAG-3 with the anti-LAG-3 antibody or antigen-binding portion according to claim 41. Thus, claim 50 is drawn to a vast genus of anti-LAG-3 antibodies and antigen-binding portions thereof having no identified structural sequence, and that are identified by function only.
The instant specification discloses seven functional antibodies that bind to LAG-3. The instant specification further identifies each antibody by the specific amino acid sequences to VH and VL chains, DNA sequences, and specific H-CDR1-3, and L-CDR1-3 amino acid sequences along with three different heavy and light chain constant regions.
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Thus, the instant specification identifies making seven structurally distinct anti-LAG-3 antibodies and describes the specific amino acid structural sequence for the H-CDR1-3 and L-CDR1-3 along with the heavy and light chain sequences. The specification fails to disclose any other sequence variant antibodies that function to bind LAG-3.
To provide adequate written description and evidence of possession of the claimed antibody genus, the instant specification can structurally describe representative antibody variants that function to bind LAG-3, or describe structural features common to the members of the genus, which features constitute a substantial portion of the genus. Alternatively, the specification can show that the claimed invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics (see University of California v. Eli Lilly and Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) and Enzo Biochem, Inc. V. Gen-Probe Inc.).
In this case, the only factor present in the claims is a recitation of the antibody function, “anti-LAG-3” and no sequence structure. The instant specification fails to describe structural features common to the members of the antibody genus, which features constitute a substantial portion of the genus because the instant specification fails to disclose representative antibody variant sequences that function as claimed. A definition by function does not suffice to define the genus because it is only an indication of what the antibody does, rather than what it is. Other than for the antibodies disclosed in Tables 8 and 9, the specification fails to provide an open amino acid sequence structure that contain the claimed functional characteristics. The instant specification fails to describe a representative number of antibody sequence variants for the genus of antibodies that function as claimed. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus required to make the claimed antibodies.
The claims broadly encompass any antibody or antigen-binding portion that binds to LAG-3. Applicants have not established any reasonable structure-function correlation with regards to the sequences in the antibody that can be altered and still maintain LAG-3 binding function. Given the well-known high level of polymorphism of antibody sequences and structure, as is evidenced by Teplyakov, et al., (MABS, 2016, 8(6):1045-1063), the skilled artisan would not have been in possession of the vast repertoire of antibodies encompassed by the claimed invention. One could not reasonably or predictably extrapolate the structure of a single antibody comprising any sequence variant that binds human LAG-3. Therefore, one could not readily envision members of the broadly claimed genus.
Although Applicants may argue that it is possible to screen for antibodies that bind LAG-3 and function as claimed, the court found in (Rochester v. Searle, 358 F.3d 916, Fed Cir., 2004) that screening assays are not sufficient to provide adequate written description for an invention because they are merely a wish or plan for obtaining the claimed chemical invention. “As we held in Lilly, “[a]n adequate written description of a DNA … ‘requires a precise definition, such as by structure, formula, chemical name, or physical properties,’ not a mere wish or plan for obtaining the claimed chemical invention.” 119 F.3d at 1566 (quoting Fiers, 984 F.2d at 1171). For reasons stated above, that requirement applies just as well to non-DNA (or RNA) chemical inventions.” Knowledge of screening methods provides no information about the structure of any future antibodies yet to be discovered that may function as claimed. The LAG-3 antigen epitope provides no information about the structure of an antibody that binds to it.
Given the lack of representative examples to support the full scope of the claimed variant antibodies, and lack of reasonable structure-function correlation with regards to the unknown variable amino acid sequences that provide LAG-3 binding function, the present claim lacks adequate written description. Thus, the specification does not provide an adequate written description of antibody variants that bind human LAG-3 and compete for binding with the anti-LAG-3 antibody of claim 41 that is required to practice the claimed invention.
7. Claims 58-61 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for cancer that expresses LAG-3, does not reasonably provide enablement for treatment of any cancer. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
The factors to be considered in determining whether undue experimentation is required are summarized In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988). The court in Wands states: "Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is 'undue,' not 'experimentation.' " (Wands, 8 USPQ2d 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. "Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations." (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: (1) the quantity of experimentation necessary, (2) the amount or direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.
The claims are drawn to a method for treating cancer in a patient by administering the anti-LAG-3 antibody of claim 41. Claim 61 further recites a method for treating cancer in a patient by administering the immunoadhesion molecule of claim 57.
The specification discloses binding affinity tests using CHO-S cells transiently transfected to express LAG-3.
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The specification further disclosed the ability of the antibodies to block LAG-3 binding to MHC-II surface molecules expressed on a human melanoma cell line, A375, in vitro. The specification also discloses the blocking of LAG-3 and MHC-II binding in vitro through the use of Jurkat cells to express LAG-3 and Raji cells expressing MHC-II in Figure 4 below. The Jurkat cells overexpressing LAG-3 were also used to show the anti-LAG antibodies ability to down-modulate LAG-3 expression. In vivo experiments were also disclosed demonstrating the antibodies ability to block binding between LAG-3 and MHC-II within murine model of fibrosarcoma and lung cancer, and a mouse xenograft model using a human melanoma cell line.
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525
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Relevant art teaches that LAG-3 is co-expressed with PD-1 on tumor infiltrating cells in murine models of cancer and co-blockade of the LAG-3 and PD-1 pathways have been shown to improve anti-tumor T cell responses. (See Anderson (Immunity, 2017, 44(5):989-1004).
One cannot extrapolate the disclosure of the specification to the scope of the claims because the nature of the invention operates by blocking a specific binding reaction between LAG-3 and MHC-II expressed on cell surfaces requiring both components to be present for the antibody to exert any effect on a tumor microenvironment. The state of the art provides further evidence that the LAG-3 antigen must be present for the antibody to be able to provide treatment for a cancer patient. The breadth of the claims would require that the antibody is able to treat cancer even if LAG-3 and MHC-II binding would have no effect on the tumor progression and the specification provides no guidance for how the antibody could provide treatment for a cancer patient in this case.
Reasonable correlation must exist between the scope of the claims and scope of enablement set forth, and it cannot be reasonably predicted that anti-LAG-3 antibodies will predictably function as claimed.
Therefore, in view of the novel nature of the invention, the state of the art, the breadth of the claims, lack of guidance in the specification, and the absence of working examples for treating cancer not expressing LAG-3, it would require undue experimentation for one skilled in the art to practice the invention as broadly claimed.
Examiner Suggestion: Amend claims 58 and 61 to recite “A method for treating LAG-3-expressing cancer in a patient,”.
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.
8. Claims 52-55 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No.11834503 B2 (Hereinafter referred to as Patent ‘503).
Patent ‘503 claims an isolated nucleic acid molecule encoding a heavy and light chain sequence of an anti-LAG-3 antibody or an antigen-binding portion thereof, wherein said antibody comprises the H-CDR1-3 and L-CDR1-3 amino acid sequences of SEQ ID NOs: 41, 42, 43, 44, 45, and 40, respectively. The claimed nucleic acid molecule further encodes a heavy chain region comprising the amino acid sequence of SEQ ID NO: 7 and 30, and the light chain region comprising the amino acid sequence of SEQ ID NO:8 and 34. The claimed anti-LAG-3 antibody also (See alignments below). Patent ‘503 further claims a host cell and vector, including an expression control sequence, comprising the nucleic acid molecule of the anti-LAG3 antibody or antigen-binding portion from above. Patent ‘503 also claims a method for producing an anti-LAG3 antibody or antigen-binding portion by culturing a host cell under conditions suitable for expression of the antibody o antigen-binding portion and isolating the resulting antibody or antigen-binding portion.
SEQ ID NOs:41, 42, and 43 100% match SEQ ID NO:7 (Patent ‘503):
US-17-834-497-7
Filing date in PALM: 2022-06-07
Sequence 7, US/17834497
Publication No. US20220363757A1
GENERAL INFORMATION
APPLICANT: SYMPHOGEN A/S
TITLE OF INVENTION: ANTI-LAG-3 ANTIBODIES AND COMPOSITIONS
FILE REFERENCE: 022675.WO057
CURRENT APPLICATION NUMBER: US/17/834,497
CURRENT FILING DATE: 2022-06-07
PRIOR APPLICATION NUMBER: 62/407,678
PRIOR FILING DATE: 2016-10-13
NUMBER OF SEQ ID NOS: 74
SEQ ID NO 7
LENGTH: 122
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
NAME/KEY: source
OTHER INFORMATION: /note="Description of Artificial Sequence: Synthetic
polypeptide"
%
Result Query Filing
No. Score Match Length ID Date Dups Description
-------------------------------------------------------------------------------------------------------------
1 181.6 87.7 122 US-16-340-855-7 2019-04-10 5 ANTI-LAG-3 ANTIBODIES AND COMPOSITIONS
ALIGNMENT:
Query Match 87.7%; Score 181.6; Length 122;
Best Local Similarity 37.9%;
Matches 33; Conservative 0; Mismatches 0; Indels 54; Gaps 2;
Qy 1 GESFSGYY-----------------INHSGST---------------------------- 15
|||||||| |||||||
Db 26 GESFSGYYWNWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTISVDTSKTQFSLKLSSV 85
Qy 16 ---------CARGWDLLDWNDYWNEYW 33
||||||||||||||||||
Db 86 TAADTAVYYCARGWDLLDWNDYWNEYW 112
SEQ ID NOs:44, 45, and 40 100% match SEQ ID NO:8 (Patent ‘503):
US-17-834-497-8
Filing date in PALM: 2022-06-07
Sequence 8, US/17834497
Publication No. US20220363757A1
GENERAL INFORMATION
APPLICANT: SYMPHOGEN A/S
TITLE OF INVENTION: ANTI-LAG-3 ANTIBODIES AND COMPOSITIONS
FILE REFERENCE: 022675.WO057
CURRENT APPLICATION NUMBER: US/17/834,497
CURRENT FILING DATE: 2022-06-07
PRIOR APPLICATION NUMBER: 62/407,678
PRIOR FILING DATE: 2016-10-13
NUMBER OF SEQ ID NOS: 74
SEQ ID NO 8
LENGTH: 107
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
NAME/KEY: source
OTHER INFORMATION: /note="Description of Artificial Sequence: Synthetic
polypeptide"
%
Result Query Filing
No. Score Match Length ID Date Dups Description
-------------------------------------------------------------------------------------------------------------
23 83.8 76.9 107 US-09-434-870-2 1999-11-04 161 Methods of Optimizing Antibody Variable Region Binding Affinity
ALIGNMENT:
Query Match 76.9%; Score 83.8; Length 107;
Best Local Similarity 27.8%;
Matches 20; Conservative 0; Mismatches 0; Indels 52; Gaps 2;
Qy 1 QSVSS-----------------YDAS---------------------------------- 9
||||| ||||
Db 27 QSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVY 86
Qy 10 -CQQRSNWPLTF 20
|||||||||||
Db 87 YCQQRSNWPLTF 98
SEQ ID NO:7 100% match SEQ ID NO:7 (Patent ‘503):
US-17-834-497-7
Filing date in PALM: 2022-06-07
Sequence 7, US/17834497
Publication No. US20220363757A1
GENERAL INFORMATION
APPLICANT: SYMPHOGEN A/S
TITLE OF INVENTION: ANTI-LAG-3 ANTIBODIES AND COMPOSITIONS
FILE REFERENCE: 022675.WO057
CURRENT APPLICATION NUMBER: US/17/834,497
CURRENT FILING DATE: 2022-06-07
PRIOR APPLICATION NUMBER: 62/407,678
PRIOR FILING DATE: 2016-10-13
NUMBER OF SEQ ID NOS: 74
SEQ ID NO 7
LENGTH: 122
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
NAME/KEY: source
OTHER INFORMATION: /note="Description of Artificial Sequence: Synthetic
polypeptide"
%
Result Query Filing
No. Score Match Length ID Date Dups Description
-------------------------------------------------------------------------------------------------------------
1 672 100.0 122 US-16-340-855-7 2019-04-10 5 ANTI-LAG-3 ANTIBODIES AND COMPOSITIONS
ALIGNMENT:
Query Match 100.0%; Score 672; Length 122;
Best Local Similarity 100.0%;
Matches 122; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLQQWGAGLLRPSETLSLTCAVYGESFSGYYWNWIRQPPGKGLEWIGEINHSGSTNYN 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLQQWGAGLLRPSETLSLTCAVYGESFSGYYWNWIRQPPGKGLEWIGEINHSGSTNYN 60
Qy 61 PSLKSRVTISVDTSKTQFSLKLSSVTAADTAVYYCARGWDLLDWNDYWNEYWGQGTLVTV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 PSLKSRVTISVDTSKTQFSLKLSSVTAADTAVYYCARGWDLLDWNDYWNEYWGQGTLVTV 120
Qy 121 SS 122
||
Db 121 SS 122
SEQ ID NO:8 100% match SEQ ID NO:8 (Patent ‘503):
US-17-834-497-8
Filing date in PALM: 2022-06-07
Sequence 8, US/17834497
Publication No. US20220363757A1
GENERAL INFORMATION
APPLICANT: SYMPHOGEN A/S
TITLE OF INVENTION: ANTI-LAG-3 ANTIBODIES AND COMPOSITIONS
FILE REFERENCE: 022675.WO057
CURRENT APPLICATION NUMBER: US/17/834,497
CURRENT FILING DATE: 2022-06-07
PRIOR APPLICATION NUMBER: 62/407,678
PRIOR FILING DATE: 2016-10-13
NUMBER OF SEQ ID NOS: 74
SEQ ID NO 8
LENGTH: 107
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
NAME/KEY: source
OTHER INFORMATION: /note="Description of Artificial Sequence: Synthetic
polypeptide"
%
Result Query Filing
No. Score Match Length ID Date Dups Description
-------------------------------------------------------------------------------------------------------------
1 554 100.0 107 US-09-434-870-2 1999-11-04 161 Methods of Optimizing Antibody Variable Region Binding Affinity
ALIGNMENT:
Query Match 100.0%; Score 554; Length 107;
Best Local Similarity 100.0%;
Matches 107; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPA 60
Qy 61 RFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPLTFGGGTKVEIK 107
|||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPLTFGGGTKVEIK 107
SEQ ID NO:30 100% match SEQ ID NO:30 (Patent ‘503):
US-17-834-497-30
Filing date in PALM: 2022-06-07
Sequence 30, US/17834497
Publication No. US20220363757A1
GENERAL INFORMATION
APPLICANT: SYMPHOGEN A/S
TITLE OF INVENTION: ANTI-LAG-3 ANTIBODIES AND COMPOSITIONS
FILE REFERENCE: 022675.WO057
CURRENT APPLICATION NUMBER: US/17/834,497
CURRENT FILING DATE: 2022-06-07
PRIOR APPLICATION NUMBER: 62/407,678
PRIOR FILING DATE: 2016-10-13
NUMBER OF SEQ ID NOS: 74
SEQ ID NO 30
LENGTH: 330
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
NAME/KEY: source
OTHER INFORMATION: /note="Description of Artificial Sequence: Synthetic
polypeptide"
%
Result Query Filing
No. Score Match Length ID Date Dups Description
-------------------------------------------------------------------------------------------------------------
1 1767 100.0 330 US-13-010-403-45 2011-01-20 66 Anticoagulant Antidotes
ALIGNMENT:
Query Match 100.0%; Score 1767; Length 330;
Best Local Similarity 100.0%;
Matches 330; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 60
Qy 61 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGG 120
Qy 121 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 180
Qy 181 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 240
Qy 241 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 300
Qy 301 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 330
||||||||||||||||||||||||||||||
Db 301 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 330
SEQ ID NO:34 100% match SEQ ID NO:34 (Patent ‘503):
US-17-834-497-34
Filing date in PALM: 2022-06-07
Sequence 34, US/17834497
Publication No. US20220363757A1
GENERAL INFORMATION
APPLICANT: SYMPHOGEN A/S
TITLE OF INVENTION: ANTI-LAG-3 ANTIBODIES AND COMPOSITIONS
FILE REFERENCE: 022675.WO057
CURRENT APPLICATION NUMBER: US/17/834,497
CURRENT FILING DATE: 2022-06-07
PRIOR APPLICATION NUMBER: 62/407,678
PRIOR FILING DATE: 2016-10-13
NUMBER OF SEQ ID NOS: 74
SEQ ID NO 34
LENGTH: 107
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
NAME/KEY: source
OTHER INFORMATION: /note="Description of Artificial Sequence: Synthetic
polypeptide"
%
Result Query Filing
No. Score Match Length ID Date Dups Description
-------------------------------------------------------------------------------------------------------------
1 553 100.0 107 US-08-422-091-8 1995-04-14 3137 Altered Polypeptides with Increased Half-Life
ALIGNMENT:
Query Match 100.0%; Score 553; Length 107;
Best Local Similarity 100.0%;
Matches 107; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD 60
Qy 61 SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 107
|||||||||||||||||||||||||||||||||||||||||||||||
Db 61 SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 107
9. Claims 41-51 and 56-61 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No.11390676 (Hereinafter referred to as Patent ‘676) in view of Triebel (US2015/0259420 A1 pub. 9/17/2015, cited on IDS 10/19/2023).
Patent ‘676 claims an anti-LAG-3 antibody or an antigen-binding portion thereof, wherein said antibody comprises the H-CDR1-3 and L-CDR1-3 amino acid sequences of SEQ ID NOs: 41, 42, 43, 44, 45, and 40, respectively. Patent ‘676 further claims the anti-LAG-3 antibody as comprising a heavy chain with the amino acid sequence of SEQ ID NOs: 7 and 30 and a light chain with the amino acid sequences of SEQ ID NOs: 8 and 34. (See alignments below).
Patent ‘676 claims the anti-LAG-3 antibody or antigen-binding portion, wherein the antibody or antigen-binding portion has at least one property selected from: a) at a concentration of 20 µg/mL, reduces the binding of human LAG-3 to human MHC class II on A375 cells by greater than 85% compared to a negative control antibody as determined by a flow cytometric competition assay; b) at a concentration of 20 µg/mL, reduces the binding of human LAG-3 to human MHC class II on A375 cells to between 35% and 85% compared to a negative control antibody as determined by a flow cytometric competition assay; c) blocks binding between human LAG-3 expressed on Jurkat cells and human MHC class II expressed on Raji cells; d) binds to human LAG-3 with an EC50 of 0.1 nM or less as measured by flow cytometry; e) binds to cynomolgus LAG-3 with an EC50 of 0.3 nM or less as measured by flow cytometry; f) binds to human LAG-3 with a KD of 3.0 x 10-8 M or less as measured by surface plasmon resonance; g) binds to cynomolgus LAG-3 with a KD of 1.5 x 10-7 M or less as measured by surface plasmon resonance; h) binds to mouse LAG-3 with a KD of 3.5 x 10-8 M or less as measured by surface plasmon resonance; i) stimulates IL-2 production in Staphylococcal enterotoxin B (SEB) treated human peripheral blood mononuclear cells (PBMCs); j) reduces cellular levels of LAG-3 in human T cells; k) reduces soluble levels of LAG-3 in the culture of human T cells; 1) induces tumor growth regression in vivo; m) delays tumor growth in vivo; and n) does not bind to the same epitope of human LAG-3 as antibody 25F7-Lag3.5.
Patent ‘676 further claims the anti-LAG-3 antibody is an isotype of IgG, and further a subclass IgG1 and a bispecific molecule comprising the anti-LAG-3 antibody and the antigen-binding portion of another, distinct antibody. Patent ‘676 claims a pharmaceutical composition of the anti-LAG-3 antibody or a method for treating cancer by administering the anti-LAG-3 antibody.
Patent ‘676 does not claim the anti-LAG-3 antibody that binds to an epitope of human LAG-3 having amino acid residues H85, P86, A87, P89, S91, W92, and G93 of SEQ ID NO: 68. However, patent ‘676 claims the exact same antibody as the present claimed application, it would follow that it would bind to the same LAG-3 epitopes.
Patent ‘676 does not claim a method of treating cancer by administration of an immunoadhesion molecule comprising the anti-LAG-3 antibody and one or more other proteins or peptides. Patent ‘676 does not claim the anti-LAG-3 antibody of isotype IgG subclass IgG1 where one or both of the amino acid residues at position 234 and 235 are mutated from Leu to Ala or the subclass is IgG4 and the amino acid residue at position 228 is mutated from Ser to Pro.
Triebel teaches an anti-LAG-3 antibody comprising an isotype IgG subclass IgG1 where one or both of the amino acid residues at positions 234 and 235 are mutated from Leu to Ala, or the antibody is of isotype IgG subclass IgG4 and the amino acid residue at position 228 is mutated from Ser to Pro. (See Triebel, pg. 16 [0113]).
Triebel teaches that the anti-LAG-3 antibody can be linked to an immunoadhesion molecule and used for treating cancer in subjects. (See Triebel, pg. 31 [0273], also claim 14).
It would have been prima facie obvious to a person of ordinary skill in the art prior to the effective filing date to use the antibody of Patent ‘676 with the methods and embodiments taught in Triebel to produce the anti-LAG-3 antibody as claimed in the present application. It would have been obvious because Triebel claims an anti-LAG-3 antibody and teaches methods and uses of that antibody that are similar with the current and patented antibody. Therefore, it would have been obvious for a person of ordinary skill in the art to combine the antibody of Patent ‘676 with the taught methods and embodiments of Triebel with a reasonable expectation of success at producing the claimed antibodies of the present application.
SEQ ID NOs:41, 42, and 43 100% match SEQ ID NO:7 (Patent ‘676):
US-16-340-855-7
(NOTE: this sequence has 5 duplicates in the database searched.
See complete list at the end of this report)
Sequence 7, US/16340855
Publication No. US20220056126A1
GENERAL INFORMATION
APPLICANT: SYMPHOGEN A/S
TITLE OF INVENTION: ANTI-LAG-3 ANTIBODIES AND COMPOSITIONS
FILE REFERENCE: 022675.WO057
CURRENT APPLICATION NUMBER: US/16/340,855
CURRENT FILING DATE: 2019-04-10
PRIOR APPLICATION NUMBER: 62/407,678
PRIOR FILING DATE: 2016-10-13
NUMBER OF SEQ ID NOS: 74
SEQ ID NO 7
LENGTH: 122
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
NAME/KEY: source
OTHER INFORMATION: /note="Description of Artificial Sequence: Synthetic
polypeptide"
Query Match 87.7%; Score 181.6; Length 122;
Best Local Similarity 37.9%;
Matches 33; Conservative 0; Mismatches 0; Indels 54; Gaps 2;
Qy 1 GESFSGYY-----------------INHSGST---------------------------- 15
|||||||| |||||||
Db 26 GESFSGYYWNWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTISVDTSKTQFSLKLSSV 85
Qy 16 ---------CARGWDLLDWNDYWNEYW 33
||||||||||||||||||
Db 86 TAADTAVYYCARGWDLLDWNDYWNEYW 112
SEQ ID NOs:44, 45, and 40 100% match SEQ ID NO:8 (Patent ‘676):
US-16-340-855-8
Filing date in PALM: 2019-04-10
Sequence 8, US/16340855
Publication No. US20220056126A1
GENERAL INFORMATION
APPLICANT: SYMPHOGEN A/S
TITLE OF INVENTION: ANTI-LAG-3 ANTIBODIES AND COMPOSITIONS
FILE REFERENCE: 022675.WO057
CURRENT APPLICATION NUMBER: US/16/340,855
CURRENT FILING DATE: 2019-04-10
PRIOR APPLICATION NUMBER: 62/407,678
PRIOR FILING DATE: 2016-10-13
NUMBER OF SEQ ID NOS: 74
SEQ ID NO 8
LENGTH: 107
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
NAME/KEY: source
OTHER INFORMATION: /note="Description of Artificial Sequence: Synthetic
polypeptide"
%
Result Query Filing
No. Score Match Length ID Date Dups Description
-------------------------------------------------------------------------------------------------------------
23 83.8 76.9 107 US-09-434-870-2 1999-11-04 161 Methods of Optimizing Antibody Variable Region Binding Affinity
ALIGNMENT:
Query Match 76.9%; Score 83.8; Length 107;
Best Local Similarity 27.8%;
Matches 20; Conservative 0; Mismatches 0; Indels 52; Gaps 2;
Qy 1 QSVSS-----------------YDAS---------------------------------- 9
||||| ||||
Db 27 QSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVY 86
Qy 10 -CQQRSNWPLTF 20
|||||||||||
Db 87 YCQQRSNWPLTF 98
SEQ ID NO:7 100% match SEQ ID NO:7 (Patent ‘676):
US-16-340-855-7
(NOTE: this sequence has 5 duplicates in the database searched.
See complete list at the end of this report)
Sequence 7, US/16340855
Publication No. US20220056126A1
GENERAL INFORMATION
APPLICANT: SYMPHOGEN A/S
TITLE OF INVENTION: ANTI-LAG-3 ANTIBODIES AND COMPOSITIONS
FILE REFERENCE: 022675.WO057
CURRENT APPLICATION NUMBER: US/16/340,855
CURRENT FILING DATE: 2019-04-10
PRIOR APPLICATION NUMBER: 62/407,678
PRIOR FILING DATE: 2016-10-13
NUMBER OF SEQ ID NOS: 74
SEQ ID NO 7
LENGTH: 122
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
NAME/KEY: source
OTHER INFORMATION: /note="Description of Artificial Sequence: Synthetic
polypeptide"
Query Match 100.0%; Score 672; Length 122;
Best Local Similarity 100.0%;
Matches 122; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLQQWGAGLLRPSETLSLTCAVYGESFSGYYWNWIRQPPGKGLEWIGEINHSGSTNYN 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLQQWGAGLLRPSETLSLTCAVYGESFSGYYWNWIRQPPGKGLEWIGEINHSGSTNYN 60
Qy 61 PSLKSRVTISVDTSKTQFSLKLSSVTAADTAVYYCARGWDLLDWNDYWNEYWGQGTLVTV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 PSLKSRVTISVDTSKTQFSLKLSSVTAADTAVYYCARGWDLLDWNDYWNEYWGQGTLVTV 120
Qy 121 SS 122
||
Db 121 SS 122
SEQ ID NO:8 100% match SEQ ID NO:8 (Patent ‘676):
US-16-340-855-8
Filing date in PALM: 2019-04-10
Sequence 8, US/16340855
Publication No. US20220056126A1
GENERAL INFORMATION
APPLICANT: SYMPHOGEN A/S
TITLE OF INVENTION: ANTI-LAG-3 ANTIBODIES AND COMPOSITIONS
FILE REFERENCE: 022675.WO057
CURRENT APPLICATION NUMBER: US/16/340,855
CURRENT FILING DATE: 2019-04-10
PRIOR APPLICATION NUMBER: 62/407,678
PRIOR FILING DATE: 2016-10-13
NUMBER OF SEQ ID NOS: 74
SEQ ID NO 8
LENGTH: 107
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
NAME/KEY: source
OTHER INFORMATION: /note="Description of Artificial Sequence: Synthetic
polypeptide"
%
Result Query Filing
No. Score Match Length ID Date Dups Description
-------------------------------------------------------------------------------------------------------------
1 554 100.0 107 US-09-434-870-2 1999-11-04 161 Methods of Optimizing Antibody Variable Region Binding Affinity
ALIGNMENT:
Query Match 100.0%; Score 554; Length 107;
Best Local Similarity 100.0%;
Matches 107; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPA 60
Qy 61 RFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPLTFGGGTKVEIK 107
|||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPLTFGGGTKVEIK 107
SEQ ID NO:30 100% match SEQ ID NO:30 (Patent ‘676):
US-16-340-855-30
Filing date in PALM: 2019-04-10
Sequence 30, US/16340855
Publication No. US20220056126A1
GENERAL INFORMATION
APPLICANT: SYMPHOGEN A/S
TITLE OF INVENTION: ANTI-LAG-3 ANTIBODIES AND COMPOSITIONS
FILE REFERENCE: 022675.WO057
CURRENT APPLICATION NUMBER: US/16/340,855
CURRENT FILING DATE: 2019-04-10
PRIOR APPLICATION NUMBER: 62/407,678
PRIOR FILING DATE: 2016-10-13
NUMBER OF SEQ ID NOS: 74
SEQ ID NO 30
LENGTH: 330
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
NAME/KEY: source
OTHER INFORMATION: /note="Description of Artificial Sequence: Synthetic
polypeptide"
%
Result Query Filing
No. Score Match Length ID Date Dups Description
-------------------------------------------------------------------------------------------------------------
1 1767 100.0 330 US-13-010-403-45 2011-01-20 66 Anticoagulant Antidotes
ALIGNMENT:
Query Match 100.0%; Score 1767; Length 330;
Best Local Similarity 100.0%;
Matches 330; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 60
Qy 61 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGG 120
Qy 121 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 180
Qy 181 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 240
Qy 241 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 300
Qy 301 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 330
||||||||||||||||||||||||||||||
Db 301 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 330
SEQ ID NO:34 100% match SEQ ID NO:34 (Patent ‘676):
US-16-340-855-34
Filing date in PALM: 2019-04-10
Sequence 34, US/16340855
Publication No. US20220056126A1
GENERAL INFORMATION
APPLICANT: SYMPHOGEN A/S
TITLE OF INVENTION: ANTI-LAG-3 ANTIBODIES AND COMPOSITIONS
FILE REFERENCE: 022675.WO057
CURRENT APPLICATION NUMBER: US/16/340,855
CURRENT FILING DATE: 2019-04-10
PRIOR APPLICATION NUMBER: 62/407,678
PRIOR FILING DATE: 2016-10-13
NUMBER OF SEQ ID NOS: 74
SEQ ID NO 34
LENGTH: 107
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
NAME/KEY: source
OTHER INFORMATION: /note="Description of Artificial Sequence: Synthetic
polypeptide"
%
Result Query Filing
No. Score Match Length ID Date Dups Description
-------------------------------------------------------------------------------------------------------------
1 553 100.0 107 US-08-422-091-8 1995-04-14 3137 Altered Polypeptides with Increased Half-Life
ALIGNMENT:
Query Match 100.0%; Score 553; Length 107;
Best Local Similarity 100.0%;
Matches 107; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD 60
Qy 61 SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 107
|||||||||||||||||||||||||||||||||||||||||||||||
Db 61 SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 107
10. Claims 41-61 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 54-56, 60-70, and 72 of copending Application No.18444187 (Hereinafter referred to as Application ‘187) in view of Triebel (US2015/0259420 A1 pub. 9/17/2015, cited on IDS 10/19/2023).
Application ‘187 claims an anti-LAG-3 antibody or an antigen-binding portion thereof, wherein said antibody comprises the H-CDR1-3 and L-CDR1-3 amino acid sequences of SEQ ID NOs:318-323, respectively (Current application SEQ ID NOs: 41, 42, 43, 44, 45, and 40). Application ‘187 further claims the anti-LAG-3 antibody as comprising a heavy chain with the amino acid sequence of SEQ ID NOs: 316 and 375 (Current Application SEQ ID NOs: 7 and 30) and a light chain with the amino acid sequences of SEQ ID NOs: 317 and 378 (Current Application SEQ ID NOs: 8 and 34). (See alignments below).
Application ‘187 claims the anti-LAG-3 antibody or antigen-binding portion, wherein the antibody or antigen-binding portion has at least one property selected from: a) at a concentration of 20 µg/mL, reduces the binding of human LAG-3 to human MHC class II on A375 cells by greater than 85% compared to a negative control antibody as determined by a flow cytometric competition assay; b) at a concentration of 20 µg/mL, reduces the binding of human LAG-3 to human MHC class II on A375 cells to between 35% and 85% compared to a negative control antibody as determined by a flow cytometric competition assay; c) blocks binding between human LAG-3 expressed on Jurkat cells and human MHC class II expressed on Raji cells; d) binds to human LAG-3 with an EC50 of 0.1 nM or less as measured by flow cytometry; e) binds to cynomolgus LAG-3 with an EC50 of 0.3 nM or less as measured by flow cytometry; f) binds to human LAG-3 with a KD of 3.0 x 10-8 M or less as measured by surface plasmon resonance; g) binds to cynomolgus LAG-3 with a KD of 1.5 x 10-7 M or less as measured by surface plasmon resonance; h) binds to mouse LAG-3 with a KD of 3.5 x 10-8 M or less as measured by surface plasmon resonance; i) stimulates IL-2 production in Staphylococcal enterotoxin B (SEB) treated human peripheral blood mononuclear cells (PBMCs); j) reduces cellular levels of LAG-3 in human T cells; k) reduces soluble levels of LAG-3 in the culture of human T cells; 1) induces tumor growth regression in vivo; m) delays tumor growth in vivo; and n) does not bind to the same epitope of human LAG-3 as antibody 25F7-Lag3.5.
Application ‘187 claims a pharmaceutical composition of the anti-LAG-3 antibody and a pharmaceutically acceptable excipient and a method for treating cancer by administering the anti-LAG-3 antibody including hematological malignancies and solid tumors. Application ‘554 claims further administering to the patient radiation therapy, chemotherapeutic agent, an anti-neoplastic agent, or an anti-angiogenic agent.
Application ‘187 claims a multispecific binding molecule comprising a LAG-3 antibody and a PD-1 antibody.
Application ‘187 does not claim the anti-LAG-3 antibody that binds to an epitope of human LAG-3 having amino acid residues H85, P86, A87, P89, S91, W92, and G93 of SEQ ID NO: 68. However, application ‘187 claims the exact same antibody as the present claimed application it would follow that it would bind to the same LAG-3 epitopes.
Application ‘187 does not claim the anti-LAG-3 antibody of isotype IgG, or further a subclass IgG1 and further wherein the IgG is subclass IgG1 and one or both of the amino acid residues at position 234 and 235 are mutated from Leu to Ala or the subclass is IgG4 and the amino acid residue at position 228 is mutated from Ser to Pro.
Application ‘187 does not claim the isolated nucleic acid molecule comprising the nucleotide sequence that encodes the heavy chain and the light chain sequence of the anti-LAG-3 antibody, a vector comprising the isolated nucleic acid molecule and an expression control sequence, and a host cell comprising the nucleotide sequence encoding for the anti-LAG-3 antibody and a method for producing the anti-LAG-3 antibody by culturing the host cell under suitable conditions for expression of the antibody.
Application ‘187 does not claim an immunoadhesion molecule comprising the anti-LAG-3 antibody and one or more proteins or peptides or a method for treating cancer using the immunoadhesion molecule.
Triebel teaches a method of making an anti-LAG-3 antibody using a nucleotide sequence of heavy and light chain regions of the antibody, expressing them in a vector through a host cell. (See Triebel, claims 29-31 and 35-40).
Triebel teaches an anti-LAG-3 antibody comprising an isotype IgG subclass IgG1 that comprises one or both of the amino acid residues at positions 234 and 235 are mutated from Leu to Ala, or the antibody is of isotype IgG subclass IgG4 and the amino acid residue at position 228 is mutated from Ser to Pro. (See Triebel, pg. 16 [0113]).
Triebel teaches that the anti-LAG-3 antibody can be linked to an immunoadhesion molecule and used for treating cancer in subjects. (See Triebel, pg. 31 [0273], also claim 14).
It would have been prima facie obvious to a person of ordinary skill in the art prior to the effective filing date to use the antibody of Application ‘187 with the methods and embodiments taught in Triebel to produce the anti-LAG-3 antibody as claimed in the present application. It would have been obvious because the method of encoding a protein in a nucleotide sequence in a vector and expressing it through a host cell is widely known in the art as a reliable way to produce antibodies and Triebel claims an anti-LAG-3 antibody and teaches methods and uses of that antibody that are similar and compatible with the current and co-pending applications’ antibody. Therefore, it would have been obvious for a person of ordinary skill in the art to combine the antibody of application ‘187 with the taught methods and embodiments of Triebel with a reasonable expectation of success at producing the claimed antibodies of the present application.
This is a provisional nonstatutory double patenting rejection.
SEQ ID NOs:41, 42, and 43 100% match SEQ ID NO:316 (Application ‘187):
US-18-444-187-316
Filing date in PALM: 2024-02-16
Sequence 316, US/18444187
Publication No. US20240270848A1
GENERAL INFORMATION
APPLICANT: SYMPHOGEN A/S (en)
TITLE OF INVENTION: COMBINATION THERAPIES TARGETING PD-1, TIM-3, AND LAG-3 (en)
FILE REFERENCE: 022675.EP158
CURRENT APPLICATION NUMBER: US/18/444,187
CURRENT FILING DATE: 2024-02-16
NUMBER OF SEQ ID NOS: 397
SEQ ID NO 316
LENGTH: 122
TYPE: PRT
FEATURE:
NAME/KEY: REGION
LOCATION: 1..122
QUALIFIERS: note = source = /note="Description of Artificial Sequence:
Synthetic polypeptide"
FEATURE:
NAME/KEY: source
LOCATION: 1..122
QUALIFIERS: mol_type = protein
organism = synthetic construct
%
Result Query Filing
No. Score Match Length ID Date Dups Description
-------------------------------------------------------------------------------------------------------------
1 181.6 87.7 122 US-16-340-855-7 2019-04-10 5 ANTI-LAG-3 ANTIBODIES AND COMPOSITIONS
ALIGNMENT:
Query Match 87.7%; Score 181.6; Length 122;
Best Local Similarity 37.9%;
Matches 33; Conservative 0; Mismatches 0; Indels 54; Gaps 2;
Qy 1 GESFSGYY-----------------INHSGST---------------------------- 15
|||||||| |||||||
Db 26 GESFSGYYWNWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTISVDTSKTQFSLKLSSV 85
Qy 16 ---------CARGWDLLDWNDYWNEYW 33
||||||||||||||||||
Db 86 TAADTAVYYCARGWDLLDWNDYWNEYW 112
SEQ ID NOs:44, 45, and 40 100% match SEQ ID NO:317 (Application ‘187):
US-18-444-187-317
Filing date in PALM: 2024-02-16
Sequence 317, US/18444187
Publication No. US20240270848A1
GENERAL INFORMATION
APPLICANT: SYMPHOGEN A/S (en)
TITLE OF INVENTION: COMBINATION THERAPIES TARGETING PD-1, TIM-3, AND LAG-3 (en)
FILE REFERENCE: 022675.EP158
CURRENT APPLICATION NUMBER: US/18/444,187
CURRENT FILING DATE: 2024-02-16
NUMBER OF SEQ ID NOS: 397
SEQ ID NO 317
LENGTH: 107
TYPE: PRT
FEATURE:
NAME/KEY: REGION
LOCATION: 1..107
QUALIFIERS: note = source = /note="Description of Artificial Sequence:
Synthetic polypeptide"
FEATURE:
NAME/KEY: source
LOCATION: 1..107
QUALIFIERS: mol_type = protein
organism = synthetic construct
%
Result Query Filing
No. Score Match Length ID Date Dups Description
-------------------------------------------------------------------------------------------------------------
38 83.8 76.9 107 US-09-791-153A-71 2001-02-22 343 SELECTIVE BINDING AGENTS OF OSTEOPROTEGERIN BINDING PROTEIN
ALIGNMENT:
Query Match 76.9%; Score 83.8; Length 107;
Best Local Similarity 27.8%;
Matches 20; Conservative 0; Mismatches 0; Indels 52; Gaps 2;
Qy 1 QSVSS-----------------YDAS---------------------------------- 9
||||| ||||
Db 27 QSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVY 86
Qy 10 -CQQRSNWPLTF 20
|||||||||||
Db 87 YCQQRSNWPLTF 98
SEQ ID NO:7 100% match SEQ ID NO:316 (Application ‘187):
US-18-444-187-316
Filing date in PALM: 2024-02-16
Sequence 316, US/18444187
Publication No. US20240270848A1
GENERAL INFORMATION
APPLICANT: SYMPHOGEN A/S (en)
TITLE OF INVENTION: COMBINATION THERAPIES TARGETING PD-1, TIM-3, AND LAG-3 (en)
FILE REFERENCE: 022675.EP158
CURRENT APPLICATION NUMBER: US/18/444,187
CURRENT FILING DATE: 2024-02-16
NUMBER OF SEQ ID NOS: 397
SEQ ID NO 316
LENGTH: 122
TYPE: PRT
FEATURE:
NAME/KEY: REGION
LOCATION: 1..122
QUALIFIERS: note = source = /note="Description of Artificial Sequence:
Synthetic polypeptide"
FEATURE:
NAME/KEY: source
LOCATION: 1..122
QUALIFIERS: mol_type = protein
organism = synthetic construct
%
Result Query Filing
No. Score Match Length ID Date Dups Description
-------------------------------------------------------------------------------------------------------------
1 672 100.0 122 US-16-340-855-7 2019-04-10 5 ANTI-LAG-3 ANTIBODIES AND COMPOSITIONS
ALIGNMENT:
Query Match 100.0%; Score 672; Length 122;
Best Local Similarity 100.0%;
Matches 122; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLQQWGAGLLRPSETLSLTCAVYGESFSGYYWNWIRQPPGKGLEWIGEINHSGSTNYN 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLQQWGAGLLRPSETLSLTCAVYGESFSGYYWNWIRQPPGKGLEWIGEINHSGSTNYN 60
Qy 61 PSLKSRVTISVDTSKTQFSLKLSSVTAADTAVYYCARGWDLLDWNDYWNEYWGQGTLVTV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 PSLKSRVTISVDTSKTQFSLKLSSVTAADTAVYYCARGWDLLDWNDYWNEYWGQGTLVTV 120
Qy 121 SS 122
||
Db 121 SS 122
SEQ ID NO:8 100% match SEQ ID NO:317 (Application ‘187):
US-18-444-187-317
Filing date in PALM: 2024-02-16
Sequence 317, US/18444187
Publication No. US20240270848A1
GENERAL INFORMATION
APPLICANT: SYMPHOGEN A/S (en)
TITLE OF INVENTION: COMBINATION THERAPIES TARGETING PD-1, TIM-3, AND LAG-3 (en)
FILE REFERENCE: 022675.EP158
CURRENT APPLICATION NUMBER: US/18/444,187
CURRENT FILING DATE: 2024-02-16
NUMBER OF SEQ ID NOS: 397
SEQ ID NO 317
LENGTH: 107
TYPE: PRT
FEATURE:
NAME/KEY: REGION
LOCATION: 1..107
QUALIFIERS: note = source = /note="Description of Artificial Sequence:
Synthetic polypeptide"
FEATURE:
NAME/KEY: source
LOCATION: 1..107
QUALIFIERS: mol_type = protein
organism = synthetic construct
%
Result Query Filing
No. Score Match Length ID Date Dups Description
-------------------------------------------------------------------------------------------------------------
1 554 100.0 107 US-09-791-153A-71 2001-02-22 343 SELECTIVE BINDING AGENTS OF OSTEOPROTEGERIN BINDING PROTEIN
ALIGNMENT:
Query Match 100.0%; Score 554; Length 107;
Best Local Similarity 100.0%;
Matches 107; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPA 60
Qy 61 RFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPLTFGGGTKVEIK 107
|||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPLTFGGGTKVEIK 107
SEQ ID NO:30 100% match SEQ ID NO:375 (Application ‘187):
US-18-444-187-375
Filing date in PALM: 2024-02-16
Sequence 375, US/18444187
Publication No. US20240270848A1
GENERAL INFORMATION
APPLICANT: SYMPHOGEN A/S (en)
TITLE OF INVENTION: COMBINATION THERAPIES TARGETING PD-1, TIM-3, AND LAG-3 (en)
FILE REFERENCE: 022675.EP158
CURRENT APPLICATION NUMBER: US/18/444,187
CURRENT FILING DATE: 2024-02-16
NUMBER OF SEQ ID NOS: 397
SEQ ID NO 375
LENGTH: 330
TYPE: PRT
FEATURE:
NAME/KEY: REGION
LOCATION: 1..330
QUALIFIERS: note = source = /note="Description of Artificial Sequence:
Synthetic polypeptide"
FEATURE:
NAME/KEY: source
LOCATION: 1..330
QUALIFIERS: mol_type = protein
organism = synthetic construct
%
Result Query Filing
No. Score Match Length ID Date Dups Description
-------------------------------------------------------------------------------------------------------------
1 1767 100.0 330 US-13-010-403-45 2011-01-20 167 Anticoagulant Antidotes
ALIGNMENT:
Query Match 100.0%; Score 1767; Length 330;
Best Local Similarity 100.0%;
Matches 330; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 60
Qy 61 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGG 120
Qy 121 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 180
Qy 181 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 240
Qy 241 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 300
Qy 301 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 330
||||||||||||||||||||||||||||||
Db 301 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 330
SEQ ID NO:34 100% match SEQ ID NO:378 (Patent ‘676):
US-18-444-187-378
Filing date in PALM: 2024-02-16
Sequence 378, US/18444187
Publication No. US20240270848A1
GENERAL INFORMATION
APPLICANT: SYMPHOGEN A/S (en)
TITLE OF INVENTION: COMBINATION THERAPIES TARGETING PD-1, TIM-3, AND LAG-3 (en)
FILE REFERENCE: 022675.EP158
CURRENT APPLICATION NUMBER: US/18/444,187
CURRENT FILING DATE: 2024-02-16
NUMBER OF SEQ ID NOS: 397
SEQ ID NO 378
LENGTH: 107
TYPE: PRT
FEATURE:
NAME/KEY: REGION
LOCATION: 1..107
QUALIFIERS: note = source = /note="Description of Artificial Sequence:
Synthetic polypeptide"
FEATURE:
NAME/KEY: source
LOCATION: 1..107
QUALIFIERS: mol_type = protein
organism = synthetic construct
%
Result Query Filing
No. Score Match Length ID Date Dups Description
-------------------------------------------------------------------------------------------------------------
1 553 100.0 107 US-09-301-593A-20 1999-04-29 7075 FAP-specific Antibody with Improved Producibility
ALIGNMENT:
Query Match 100.0%; Score 553; Length 107;
Best Local Similarity 100.0%;
Matches 107; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD 60
Qy 61 SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 107
|||||||||||||||||||||||||||||||||||||||||||||||
Db 61 SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 107
Conclusion
11. Claims 41-61 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LINDSAY DUNN whose telephone number is (571)272-5825. The examiner can normally be reached Monday-Friday 8-4:30.
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, Samira Jean-Louis can be reached at 571-270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/LINDSAY DUNN/Examiner, Art Unit 1644
/Laura B Goddard/Primary Examiner, Art Unit 1642
Prosecution Insights