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 12/23/2025 is acknowledged.
3. Claims 82 and 84-94 are pending.
4. Applicant’s election of the species of an antibody comprising SEQ ID NOs 33 and 43; and the IL-2 of SEQ ID NO:301 in the reply filed on 12/23/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
5. 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.
6. Applicant’s IDS documents filed on 06/25/2024 have been considered.
7. The disclosure is 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.
8. 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.
9. Claims 82 and 84 and 86-94 are 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).
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 84-94; 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.
10. Claims 82 and 84-94 are 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).
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.
11. Claims 82, 84 and 87-94 are 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).
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.
12. Claims 82 and 84-94 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 and of U.S. Patent No. 11,965,026 (PTO-892; Reference B) in view of West et al. (IDS filed on 06/25/2024; Reference 161).
U.S. Patent No. 11,965,026 claims an immunocytokine comprising an IL-2 cytokine linked to a C-terminal end of a light chain of an immunoglobulin, wherein the light chain of the immunoglobulin comprises in N- to C-terminal direction: a) a V.sub.L domain comprising CDRL1, CDRL2 and CDRL3; b) a light chain constant region, (C.sub.L); and wherein the V.sub.L domain comprises i) the CDRL1 sequence of SEQ ID NO: 37 or 40; and ii) the CDRL2 sequence of SEQ ID NO: 38 or 41 or the CDRL2 sequence of light chain sequence SEQ ID NO: 50; and iii) the CDRL3 sequence of SEQ ID NO: 39 or 42; and wherein the immunocytokine further comprises a heavy chain that comprises in N- to C-terminal direction: a) a V.sub.H domain comprising CDRH1, CDRH2 and CDRH3; and b) a heavy chain constant region (C.sub.H); and wherein the V.sub.H domain comprises i) the CDRH1 sequence of SEQ ID NO: 27 or 30; and ii) the CDRH2 sequence of SEQ ID NO: 28 or 31; and iii) the CDRH3 sequence of SEQ ID NO: 29 or 32 and the immunocytokine optionally further comprises a linker, (L) that links the IL-2 cytokine to the C-terminal end of the light chain; wherein the V.sub.H domain and V.sub.L domain are comprised by an antigen-binding site that specifically binds to hPD-L1 as defined by SEQ ID NO: 1 and that inhibits binding of PD-L1 to PD-1; wherein the V.sub.H domain is derived from the recombination of a human IGHV3 V.sub.H gene segment, a human D gene segment, and a human IGHJ5 J.sub.H gene segment, and wherein the V.sub.L domain is derived from the recombination of a human IGκV1D V.sub.κ gene segment and a human J.sub.κ gene segment; wherein the human V.sub.H gene segment is IGHV3-9*01, the human J.sub.H gene segment is IGHJ5*02, and the human V.sub.κ gene segment is IGKV1D-39*01; wherein the V.sub.H domain comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 33; wherein the heavy chain comprises the V.sub.H domain sequence of heavy chain sequence SEQ ID NO: 47, SEQ ID NO: 48, or SEQ ID NO: 49; wherein the V.sub.L domain comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 43; wherein the immunocytokine further comprises a human constant region; wherein the human constant region is an IgG1 constant region; wherein the V.sub.H domain comprises the amino acid sequence of SEQ ID NO: 33 and the V.sub.L domain comprises the amino acid sequence of SEQ ID NO: 43; wherein the IL-2 cytokine is human IL-2 (hIL-2) or a variant thereof; wherein the hIL-2 comprises or consists of the amino acid sequence of SEQ ID NO: 301 or a variant thereof comprising a modification at the N-terminus of SEQ ID NO: 301; a pharmaceutical composition comprising the immunocytokine and a pharmaceutically acceptable excipient, diluent, or carrier; a kit comprising the pharmaceutical composition and a label or instructions comprising a marketing authorization number; wherein the V.sub.H domain comprises the amino acid sequence of SEQ ID NO: 33; wherein the VL domain comprises the amino acid sequence of SEQ ID NO: 43; wherein the V.sub.H domain comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 33, and the V.sub.L domain comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 43; wherein the heavy chain comprises the amino acid sequence of the V.sub.H domain of SEQ ID NO: 47 and the V.sub.L domain comprises the amino acid sequence of SEQ ID NO: 43; wherein the heavy chain comprises the amino acid sequence of the V.sub.H domain of SEQ ID NO: 48 and the V.sub.L domain comprises the amino acid sequence of SEQ ID NO: 43; and wherein the heavy chain comprises the amino acid sequence of the V.sub.H domain of SEQ ID NO: 49 and the V.sub.L domain comprises the amino acid sequence of SEQ ID NO: 43.
The sequence identification numbers are identical between the reference and the instant application.
The claimed invention differs from the prior art in the recitation of a method of treating a PD-L1 mediated disease or condition in a human subject comprising administering the immunocytokine of claims 82 and 84-94.
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).
It would have been obvious to one of ordinary skill in the art at the time of invention to have used the immunocytokine comprising an anti-PD-L1 antibody for in vivo use in humans to treat PD-L1 mediated disease since PD-L1 blockage synergizes with IL-2 therapy and that combined IL-2 therapy and PD-L1 blockade can be used for treating human chronic infections and cancer.
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.
13. 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.
14. Claims 81, 84-90 and 92-94 are 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(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Applicant is in possession of: immunocytokines comprising antibodies comprising all 6 specified CDRs which inhibit binding of PD-L1 to PD-1, linked to IL-2.
Applicant is not in possession of: immunocytokines comprising an antibody which blocks or inhibits binding of PD-L1 to PD-1 linked to variants of IL-2.
The skilled artisan cannot envision all the antibody, IL-2 and immunocytokine possibilities recited in the instant claims.
Consequently, conception cannot be achieved until a representative description of the structural and functional properties of the claimed invention has occurred, regardless of the complexity or simplicity of the method.
Claim 84 does not require all 6 CDRs. Applicant has not included an “and” after SEQ ID NO:31 in the second to last line.
As evidenced by the art of Goel et al. (IDS filed on 06/25/2024), Khan et al. (IDS filed on 06/25/2024) and Poosarla et al. (IDS filed on 06/25/2024), antibody specificity for a particular antigen does not correlate with any particular structure for the antibodies themselves. It was well known to those skilled in the art at the time the invention was made that minor structural differences among structurally related antibodies or compositions thereof could result in substantially different binding activities. Given the lack of guidance in the specification, it is
unpredictable which antibodies with which structures would bind to hPD-L1. The specification does not disclose a correlation between the structure of the antibodies themselves and their function of binding to hPD-L1 such that a skilled artisan would have known what antibody structures possess the claimed functions.
U.S. Court of Appeals for the Federal Circuit recently decided Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017) which concerned adequate written description for claims drawn to antibodies. The Federal Circuit explained in Amgen that when an antibody is claimed,
35 U.S.C. § 112(a) requires adequate written description of the antibody itself. Amgen, 872 F.3d
at 1378-79. The Amgen court expressly stated that the so-called "newly characterized antigen"
test, which had been based on an example in USPTO-issued training materials and was noted in
dicta in several earlier Federal Circuit decisions, should not be used in determining whether there
is adequate written description under 35 U.S.C. § 112(a) for a claim drawn to an antibody. Citing
its decision in Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., the court also stressed that the
"newly characterized antigen" test could not stand because it contradicted the quid pro quo of the
patent system whereby one must describe an invention in order to obtain a patent. Amgen, 872
F.3d at 1378-79, quoting Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1345
(Fed. Cir. 2010). In view of the Amgen decision, adequate written description of a newly
characterized antigen alone should not be considered adequate written description of a claimed
antibody to that newly characterized antigen, even when preparation of such an antibody is
routine and conventional. Id.
The specification does not provide adequate written description of the claimed invention.
The legal standard for sufficiency of a patent's (or a specification's) written description is
whether that description "reasonably conveys to the artisan that the inventor had possession at
that time of the. . .claimed subject matter", Vas-Cath, Inc. V. Mahurkar, 19 U.S.P.Q.2d 1111
(Fed. Cir. 1991). In the instant case, the specification does not convey to the artisan that the
applicant had possession at the time of invention of the claimed inventions.
The claims encompass antibodies without sequences and antibodies with variants of the recited amino acid sequences. The claims recite variable region sequences containing amino acids not found in the antibodies that were actually produced in the examples in the specification which actually bind hPD-L1. The claims recite combinations of CDRs wherein the combinations encompass antibodies other than the specific antibodies produced in the examples in the specification which actually bind hPD-L1.
It is expected that all of the heavy and light chain CDRs in their proper order and in the
context of framework sequences which maintain their required conformation, are required in
order to produce a protein having antigen-binding function and that proper association of heavy
and light chain variable regions is required in order to form functional antigen binding sites.
MacCallum, et al. (IDS filed on 06/25/2024) analyzed many different antibodies for
interactions with antigen and state that although CDR3 of the heavy and light chain dominate, a
number of residues outside the standard CDR definitions make antigen contacts (see page 733,
right column) and non- contacting residues within the CDRs coincide with residues as important
in defining canonical backbone conformations (see page 735, left column). De Pascalis, et al.
(IDS filed on 06/25/2024) demonstrate that grafting of the CDRs into a human framework was performed by grafting CDR residues and maintaining framework residues that were deemed essential for preserving the structural integrity of the antigen binding site (see page
3079, right column). Although abbreviated CDR residues were used in the constructs, some
residues in all 6 CDRs were used for the constructs (see page 3080, left column). Thus it is
unpredictable as to what amino acids can be changed in the original intact antibodies disclosed in
the specification wherein the antibodies would still function. Thus, the skilled artisan cannot
envision the detailed structure of the encompassed invention and therefore conception is not
achieved until reduction to practice has occurred, regardless of the complexity or simplicity of
the method of isolation.
Adequate written description requires more than a mere statement that it is part of the
invention and a reference to a potential method of isolating it. In the instant application, the
amino acid sequence itself or isolated protein is required. See Fiers v. Revel, 25 USPQ 2d 1601
at 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Lts., 18 USPQ2d 1016. In
view of the aforementioned problems regarding description of the claimed invention, the
specification does not provide an adequate written description of the invention claimed herein.
See The Regents of the University of California v. Eli Lilly and Company, 43 USPQ2d 1398,
1404-7 (Fed. Cir. 1997). In University of California v. Eli Lilly and Co., 39 U.S.P.Q.2d 1225
(Fed. Cir. 1995) the inventors claimed a genus of DNA species encoding insulin in different
vertebrates or mammals, but had only described a single species of cDNA which encoded rat
insulin. The court held that only the nucleic acids species described in the specification(i.e.
nucleic acids encoding rat insulin) met the description requirement and that the inventors were
not entitled to a claim encompassing a genus of nucleic acids encoding insulin from other
vertebrates, mammals or humans, id. at 1240. The Federal Circuit has held that if an inventor is
"unable to envision the detailed constitution of a gene so as to distinguish it from other materials.
. .conception has not been achieved until reduction to practice has occurred", Amgen, Inc. v.
Chugai Pharmaceutical Co, Ltd., 18 U.S.P.Q.2d 016 (Fed. Cir. 1991). Attention is also directed
to the decision of The Regents of the University of California v. Eli Lilly and Company (CAFC,
July 1997) wherein is stated: "The description requirement of the patent statute requires a
description of an invention, not an indication of a result that one might achieve if one made that
invention. See In re Wilder, 736 F.2d 1516, 222 USPQ 369, 372-373 (Fed. Cir. 1984) (affirming
rejection because the specification does "little more than outlin[e] goals appellants hope the
claimed invention achieves and the problems the invention will hopefully ameliorate.").
Accordingly, naming a type of material generally known to exist, in the absence of knowledge as
to what that material consists of, is not a description of that material. Thus, as we have
previously held, a cDNA is not defined or described by the mere name "cDNA," even if
accompanied by the name of the protein that it encodes, but requires a kind of specificity usually
achieved by means of the recitation of the sequence of nucleotides that make up the cDNA." See
Fiers, 984 F.2d at 1171, 25 USPQ2d at 1606.
As such, there is insufficient written description of the required kind of structure identifying information about the corresponding makeup of the claimed antibodies, IL-2 variants and immunocytokines to demonstrate possession.
15. 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.
16. Claim 82 is rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent Application Publication 2016/0175397 (PTO-892; Reference A) in view of Gillies et al. (IDS filed on 06/25/2024; Reference 51).
U.S. Patent Application Publication 2016/0175397 teaches a method of administering a tumor-targeted human IL-2 variant immunocytokine in combination with an antibody which binds to human PD-L1 in a combination therapy in the treatment of cancer (In particular, claims, whole document); wherein the antibody comprises a human constant region and an IgG1 subclass (In particular, paragraphs [0031], [0166], [0263]).
The claimed invention differs from the prior art in the recitation of linking the IL-2 cytokine to the C-terminal end of the light chain of the immunoglobulin of claim 82.
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 Application Publication 2016/0175397 and Gillies et al. to have arrived at an immunocytokine comprising an anti-PD-L1 antibody fused to a IL-2 cytokine molecule linked to the C-terminus of the light chain 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.
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.
17. No claim is allowed.
18. 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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January 9, 2026
/Nora M Rooney/
Primary Examiner, Art Unit 1641