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 .
2. Applicant’s amendment filed on 06/11/2026 is acknowledged.
3. Claims 82 and 85-94 are pending.
4. Claims 82 and 84-94 are currently under examination as they read on a method of administering an immunocytokine comprising an antibody comprising SEQ ID NOs 33 and 43 and the IL-2 of SEQ ID NO:301.
5. The following rejections are necessitated by the amendment filed on 06/11/2026.
6. The disclosure stands objected to because of the following informalities:
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022,
That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO’s patent electronic filing system (Patent Center) (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/patents-application-process/filing-online/legal-framework-efs-web), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2)
or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE
AS FOLLOWS:
Applicant has assigned a SEQ ID numbers to at least the tripeptide sequences of SEQ ID NOs 18, 38 and 63. However, under ST.26, it is impermissible for a SEQ ID number to be used to refer to such a short amino acid sequence. 37 CFR 831 is reproduced below for applicant’s convenience (emphasis added by the examiner).
1.831 Requirements for patent applications filed on or after July 1, 2022, having nucleotide and/or amino acid sequence disclosures.
• (a) Patent applications disclosing nucleotide and/or amino acid sequences by enumeration of their residues, as defined in paragraph (b) of this section, must contain, as a separate part of the disclosure, a computer readable Sequence Listing in XML format (a "Sequence Listing XML"). Disclosed nucleotide or amino acid sequences that do not meet the definition in paragraph (b) of this section must not be included in the "Sequence Listing XML." The "Sequence Listing XML" contains the information of the nucleotide and/or amino acid sequences
disclosed in the patent application using the symbols and format in accordance with the requirements of §§ 1.832 through 1.834.
• (b) Nucleotide and/or amino acid sequences, as used in this section and §§ 1.832 through 1.835, encompass:
o (1) An unbranched sequence or linear region of a branched sequence containing 4 or more specifically defined
amino acids, wherein the amino acids form a single peptide backbone; or
o (2) An unbranched sequence or linear region of a branched sequence of 10 or more specifically defined nucleotides, wherein adjacent nucleotides are joined by:
▪ (i) A 3' to 5' (or 5' to 3') phosphodiester linkage; or
▪ (ii) Any chemical bond that results in an arrangement of adjacent nucleobases that mimics the arrangement of nucleobases in naturally occurring nucleic acids (i.e., nucleotide analogs).
• (c) Where the description or claims of a patent application discuss a sequence that is set forth in the "Sequence Listing XML" in accordance with paragraph (a) of this section, reference must be made to the sequence by use of the sequence identifier, preceded by "SEQ ID NO:" or the like in the text of the description or claims, even if the sequence is also embedded in the text of the description or claims of the patent application. Where a sequence is presented in a drawing, reference must be made to the sequence by use of the sequence identifier (§ 1.832(a) ), either in the drawing or in the Brief Description of the Drawings, where the correlation between multiple sequences in the drawing and their sequence identifiers (§ 1.832(a) ) in the Brief
Description is clear.
• (d) "Enumeration of its residues" means disclosure of a nucleotide or amino acid sequence in a patent application by listing, in order, each residue of the sequence, where the residues are represented in the manner as defined in paragraph 3(c)(i) or (ii) of WIPO Standard ST.26 (incorporated by reference, see § 1.839 ).
• (e) "Specifically defined" means any amino acid or nucleotide as defined in paragraph 3(k) of WIPO Standard ST.26.
• (f) "Amino acid" includes any D- or L-amino acid or modified amino acid as defined in paragraph 3(a) of WIPO Standard ST.26.
• (g) "Modified amino acid" includes any amino acid as described in paragraph 3(e) of WIPO Standard ST.26.
• (h) "Nucleotide" includes any nucleotide, nucleotide analog, or modified nucleotide as defined in paragraphs 3(f) and 3(g) of WIPO Standard ST.26.
• (i) "Modified nucleotide" includes any nucleotide as described in paragraph 3(f) of WIPO Standard ST.26.
• (j) A "Sequence listing XML" must not include any sequences having fewer than 10 specifically defined nucleotides, or fewer than 4 specifically defined amino acids.
[Added 87 FR 30806, May, 20, 2022, effective July 1, 2022]
It is noted that the XML sequence listing file contains no data for this tripeptide, as the
sequence identified by SEQ ID number in the table is “blank” in the XML file (i.e. no
data). While it is proper that such short three amino acid peptide sequences do not
appear in the sequence listing, applicant giving such sequences SEQ ID numbers in the
specification sets up a situation wherein the application is logically inconsistent.
Specifically, if an artisan looks at the sequence listing to determine what is at least SEQ ID
NO:18, 38 and 63 they will find it is nothing at all, whereas if they look for the same information in the specification they find it to be the tripeptides. The same term cannot have two
different meanings, and since as per 37 CFR1.831 as quoted above it is impermissible
for amino acid sequences shorter than 4 specifically defined residues to be defined via
SEQ ID number it is the specification which is in error. As such, applicant must remove
all reference to said tripeptides by way of SEQ ID number. For example, claims
must not recite “SEQ ID NO:38” and must instead spell out the tripeptide.
Similarly the specification also cannot assign a SEQ ID number for the tripeptides. Note that such changes must be made at all occurrences everywhere in the specification, including figures, drawings, and text. Note also that this issue of inappropriately assigning SEQ ID numbers to short sequences may apply to additional sequences other than SEQ ID NOs 18, 38 and 63 and that no attempt has been made by the examiner to find and catalog all such errors throughout
the specification. Appropriate correction is required.
Applicant’s response filed on 06/11/2026 attempting to fully address these issues is acknowledged.
In response It is the Examiner’s position that:
The claims still recite SEQ ID NO:38.
On pages 263-341 Applicant has amended the specification to delete reference to SEQ ID NOs 18, 38, 63, 83, 103, 123, 143, 163, 183, 249, 269, 289, 354, 371, 385, 399, 413, 427, 443, 457, 471, 485 and 499. At a minimum there is still a reference to SEQ ID No:18 on page 38, line 17. Applicant must carefully go through the specification and delete all references to each of these sequence identification numbers.
7. 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
8. Claims 82 and 86-94 stand rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 and of U.S. Patent No. 9,567,399 (IDS filed on 06/25/2024; Reference 30) in view of West et al. (IDS filed on 06/25/2024; Reference 161) and Gillies et al. (IDS filed on 06/25/2024; Reference 51) for the same reasons as set forth in the office action mailed on 01/16/2026.
U.S. Patent No. 9,567,399 claims an antibody comprising SEQ ID NOs 33 and 43 which comprise CDRs as recited in patented claims 2-7; wherein said antibody is comprised within an immunocytokine and wherein said antibody is fused to a cytokine molecule; compositions comprising excipients, diluent and carriers; and a method of treating a malignant tumour in a human in need thereof, the method comprising administering to the human the antibody or fragment thereof wherein the malignant tumour is selected from the group consisting of: melanoma, Merkel cell carcinoma, squamous non-small cell lung cancer, non-squamous non-small cell lung cancer, renal cell cancer, bladder cancer, head and neck squamous cell carcinoma, mesothelioma, virally induced cancers, cervical cancer, nasopharyngeal cancer, soft tissue sarcomas, haematological malignancies, Hodgkin's and non- Hodgkin's disease, and diffuse large B-cell lymphoma. (In particular, claims 1-21). The sequence identification numbers in U.S. Patent No. 9,567,399 are identical to the instant sequence identification numbers.
The claimed invention differs from the prior art in the recitation of the antibody being fused to IL-2 of claims 82 and 85-94; wherein the immunocytokine comprises a human constant region of claim 89; wherein the human constant region is an IgG1 constant region of claim 90; wherein the Il-2 is human IL-2 of claim 92; wherein the IL-2 is SEQ ID NO:301 or a variant thereof of claim 93.
West et al. teaches that PD-L1 blockage synergizes with IL-2 therapy and that combined IL-2 therapy and PD-L1 blockade merits consideration as a regimen for treating human chronic infections and cancer. (In particular, abstract, whole document).
Gillies et al. teaches improved immunocytokines developed utilizing fusion of cytokines to the C-terminus of the light chain. The molecules are expressed well, stable in normal buffers and have biological properties that are superior to immunocytokines made by fusion to the heavy chain. (In particular, abstract, whole document).
It would have been obvious to one of ordinary skill in the art at the time of invention to have combined the teachings of U.S. Patent 9,567,399 and West et al. to have arrived at an immunocytokine comprising an antibody comprising SEQ ID NOs 33 and 43; wherein said antibody is comprised within an immunocytokine and wherein said antibody is fused to a IL-2 cytokine molecule. It would have been obvious to have linked the cytokine to the antibody by any means, including on the C-terminus of the light chain with or without a linker, but it would have been especially obvious in view of the teachings of Gillies et al. which teaches that linking the cytokine to the C-terminus of the light chain is superior. Since U.S. Patent 9,567,399 is directed to administering the compositions in vivo in human patients, it would have been obvious to have human constant regions in the antibody, including IgG1 constant region which is commonly used. It would have been obvious to have used human IL-2 in the immunocytokine for in vivo use in humans and the sequence of SEQ ID NO:301 or a variant thereof would have been obvious because SEQ ID NO:301 is the sequence of human IL-2, but the recitation of a variant thereof encompasses any IL-2 sequence with variations from the sequence of SEQ ID NO:301.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
The rejection will not be held in abeyance. The rejection stands until the claims are amended or a terminal disclaimer is filed.
9. Claims 82 and 85-94 stand rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 and of U.S. Patent No. 9,957,323 (IDS filed on 06/25/2024; Reference 32) for the same reasons as set forth in the office action mailed on 01/16/2026.
U.S. Patent No. 9,957,323 teaches a composition comprising an anti-PD-L1 antibody; wherein the anti-PD-L1 antibody is a human IgG; wherein the anti-PD-L1 antibody comprises an effector enabled human IgG1 constant region; wherein the anti-PD-L1 antibody comprises a VH domain having amino acid sequence SEQ ID NO: 299 and a VL domain having amino acid sequence SEQ ID NO: 300; wherein the anti-PD-L1 antibody is an immunocytokine comprising human wild type or variant IL-2; and a method of treating cancer comprising administering the immunocytokine.
Reference/instant SEQ ID NOs: 300 and 45 comprise instant SEQ ID NO:43; and Reference/instant SEQ ID NOs:299, 302, 49 and 35 comprise instant SEQ ID NO:33.
The claimed invention differs from the prior art in the recitation of wherein the IL-2 is SEQ ID NO:301 or a variant thereof of claim 93.
It would have been obvious to one of ordinary skill in the art at the time of invention to have used human IL-2 in the immunocytokine for in vivo use in humans and the sequence of SEQ ID NO:301 or a variant thereof would have been obvious because SEQ ID NO:301 is the sequence of human IL-2, but the recitation of a variant thereof encompasses any IL-2 sequence with variations from the sequence of SEQ ID NO:301.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
The rejection will not be held in abeyance. The rejection stands until the claims are amended or a terminal disclaimer is filed.
10. Claims 82 and 87-94 stand rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 and of U.S. Patent No. 10,604,576 (IDS filed on 06/25/2024; Reference 33) for the same reasons as set forth in the office action mailed on 01/16/2026.
U.S. Patent No. 10,604,576 claims an antibody or a fragment thereof, which specifically binds to human PD-L1 (hPD-L1) and comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the antibody or fragment thereof comprises a CDRH1 of amino acid sequence SEQ ID NO: 27 or SEQ ID NO: 30, a CDRH2 of amino acid sequence SEQ ID NO: 28 or SEQ ID NO: 31, a CDRH3 of amino acid sequence SEQ ID NO: 29 or SEQ ID NO: 32, a CDRL1 of amino acid sequence SEQ ID NO: 37 or SEQ ID NO: 40, a CDRL2 of amino acid sequence SEQ ID NO: 38 or SEQ ID NO: 41, and a CDRL3 of amino acid sequence SEQ ID NO: 39 or SEQ ID NO: 42; wherein the V.sub.H domain comprises an amino acid sequence of SEQ ID NO:33, and the V.sub.L domain comprises an amino acid sequence of SEQ ID NO:43; comprising first and second copies of said V.sub.H domain and/or said V.sub.L domain; comprising a kappa light chain; a method of treating a malignant tumour in a human in need thereof, the method comprising administering to the human the antibody or fragment thereof according to claim 1; wherein the malignant tumour is selected from the group consisting of: melanoma, Merkel cell carcinoma, squamous non-small cell lung cancer, non-squamous non-small cell lung cancer, renal cell cancer, bladder cancer, head and neck squamous cell carcinoma, mesothelioma, virally induced cancers, cervical cancer, nasopharyngeal cancer, soft tissue sarcomas, haematological malignancies, Hodgkin's disease, non-Hodgkin's disease, and diffuse large B-cell lymphoma; and an immunocytokine comprising the antibody or fragment thereof according to claim 1 and a cytokine, and optionally further comprising a linker between the antibody or fragment thereof and the cytokine; wherein the cytokine is IL-2; a pharmaceutical composition comprising the antibody or fragment thereof according to claim 1 and a pharmaceutically acceptable carrier; a pharmaceutical composition comprising the immunocytokine according to claim 9 and a pharmaceutically acceptable carrier; further comprising an IgG1 constant region of amino acid sequence SEQ ID NO: 340; and further comprising an IgG1 constant region of amino acid sequence SEQ ID NO: 205.
The sequence identification numbers are identical between the reference and the instant application.
The reference teachings anticipate the claimed invention.
The claimed invention differs from the prior art in the recitation of wherein the IL-2 is SEQ ID NO:301 or a variant thereof of claim 93.
It would have been obvious to one of ordinary skill in the art at the time of invention to have used human IL-2 in the immunocytokine for in vivo use in humans and the sequence of SEQ ID NO:301 or a variant thereof would have been obvious because SEQ ID NO:301 is the sequence of human IL-2, but the recitation of a variant thereof encompasses any IL-2 sequence with variations from the sequence of SEQ ID NO:301. It would also have been obvious to have complied with the labeling requirements for human prescription drugs.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
The rejection will not be held in abeyance. The rejection stands until the claims are amended or a terminal disclaimer is filed.
11. No claim is allowed.
12. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
13. Any inquiry concerning this communication or earlier communications from the examiner should be directed to NORA MAUREEN ROONEY whose telephone number is (571)272-9937. The examiner can normally be reached on M-F from 8:00am to 4:30pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner' s supervisor, Misook Yu, can be reached at telephone number (571) 272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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August 25, 2026
/Nora M Rooney/
Primary Examiner, Art Unit 1641
Prosecution Insights