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
Applicant’s election of species antibody that binds to PD1 comprising VH having amino acid sequence of SEQ ID NO: 7 and VL having amino acid sequence NO: 8; an antibody that specifically binds to EGFR comprising a VH having amino acid sequence NO: 40 and VL having amino acid sequence 41; and a disease: head and neck cancer in the reply filed on 2/10/2026 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)).
Status of Application, Amendments, And/Or Claims
Claims 71-75, 80, 82, 88, 89, 94, 97, and 103-119 are pending.
Claims 82, 97, and 110-113 are withdrawn for being drawn to a non-elected species.
Claims 71-75, 80, 88, 89, 94, 103-109 and 114-119 are under examination to the extent they read on the elected invention.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The Information Disclosure Statements (IDSs) filed on 6/9/2023, 2/29/2024 and 2/10/2026 have been considered.
Drawings
New corrected drawings in compliance with 37 CFR 1.121(d) are required in this application because FIG.2A does not clearly show up D147-A9, D149-A6 in line graph. Additionally, FIG. 2C does not show up line graph for D147-A48. Applicant is advised to employ the services of a competent patent draftsperson outside the Office, as the U.S. Patent and Trademark Office no longer prepares new drawings. The corrected drawings are required in reply to the Office action to avoid abandonment of the application. The requirement for corrected drawings will not be held in abeyance.
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.
Claims 118 and 119 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.
Regarding claim 118 and 119, the phrase "sequence identity at least 95%, 96%, 97%, 98% or 99%" renders the claim indefinite because SEQ ID NO: 1 comprises only 5 amino acids and 95% is interpreted as only one amino acid variant out of 20 amino acids. Similarly, SEQ ID NO: 2 is 16 amino acids, SEQ ID NO: 3 is only 11, SEQ ID NO: 5 is 7 amino acids, SEQ ID NO: 6 comprises 9 amino acids. Therefore, any amino acid sequence having less than 19 amino acids cannot have amino acid variation of 95% or 96%. Therefore, metes and bounds of the claims cannot be determined. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 71-75, 80, 88, 89, 94, 103, and 114 -119 are rejected under 35 U.S.C. 103 as being unpatentable over Govindappa et al. (IDS, US 2013/0287802) in view of Papadopoulos et al. (IDS, US 2020/0330794).
It is noted that amino acid sequences of SEQ ID NO: 1-3 (VH CDRs1-3) and 4-6 (VL CDRs), VH having amino acid sequence of SEQ ID NO: 7(VH) and SEQ ID NO: 8 (VL) are well known in the art (see antibody Pembrolizumab, pg. 28-29Table1); and the amino acid sequence of SEQ ID NO: 34-36 (VH CDRs 1-3) and 37-39 (VL CDRs), VH having amino acid sequence of SEQ ID NO: 40 and VL having amino acid sequence of SEQ ID NO:41 are also well known in the art (see antibody Ceutximab, pg. 42 (Table2)) and search results in PE2E of 3/4/2026.
The instantly claimed invention is broadly drawn to a method of treating cancer in a human subject in need thereof comprising administering the subject: (a) an antibody
that specifically binds programmed cell death protein 1 (PD1) comprising a VH that comprises a VH CDR1, VH CDR2, and VH CDR3, wherein (i) the amino acid sequence of the VH CDR1 comprises the amino acid sequence of SEQ ID NO: 1;(ii) the amino acid sequence of the VH CDR2 comprises the amino acid sequence of SEQ ID NO: 2; and(iii) the amino acid sequence of the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 3; and a VL that comprises a VL CDR1, a VL CDR2, and a VL CDR3, wherein (i) the amino acid sequence of the VL CDR1 comprises the amino acid sequence of SEQ ID NO: 4;(ii) the amino acid sequence of the VL CDR2 comprises the amino acid sequence of SEQ ID NO: 5; and(iii) the amino acid sequence of the VL CDR3 comprises the amino acid sequence of SEQ ID NO: 6; and (b) a fusion protein that comprises a targeting moiety and an immunomodulatory moiety, wherein: i-the targeting moiety comprises an antibody that specifically binds epidermal growth factor receptor (EGFR) comprising a VH that comprises a VH CDR1, VH CDR2, and VH CDR3, wherein (i) the amino acid sequence of the VH CDR1 comprises the amino acid sequence of SEQ ID NO: 34;(ii) the amino acid sequence of the VH CDR2 comprises the amino acid sequence of SEQ ID NO: 35; and(iii) the amino acid sequence of the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 36; and a VL that comprises a VL CDR1, a VL CDR2, and a VL CDR3, wherein (i) the amino acid sequence of the VL CDR1 comprises the amino acid sequence of SEQ ID NO: 37;(ii) the amino acid sequence of the VL CDR2 comprises the amino acid sequence of SEQ ID NO: 38; and(iii) the amino acid sequence of the VL CDR3 comprises the amino acid sequence of SEQ ID NO: 39; and(ii) the immunomodulatory moiety comprises an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 56 (claim 71), wherein the antibody that specifically binds PD1 is a full-length antibody, a single chain variable fragment (scFv), a scFv2, a scFv-Fc, a Fab, a Fab', a F(ab')2, or a F(v) (claim 72), wherein the antibody is full-length and binds to PD1 and inhibits signaling (claims 73-75). The method of claim 71, wherein the cancer is a solid tumor (claim 115), wherein the cancer is breast cancer, anal cancer, pancreatic cancer, thyroid cancer, liver cancer, ovarian cancer, lung cancer, skin cancer, brain cancer, spinal cord cancer, head cancer, neck cancer, or head and neck cancer (claim 116).
Govindappa et al teach a method of treating cancer in a human subject in need thereof comprising reducing growth of cancer cells by counteracting immune tolerance of cancer cells, wherein T cell remain active and inhibit the recruitment of T-regulatory that are known to suppress the immune system's response to the tumor (see paragraph [0006]). They teach that the method comprises administering a fusion protein that comprises a targeting moiety and an immunomodulating moiety, wherein the said targeting moiety specifically binds epidermal growth factor receptor (EGFR) (the tumor targeting moiety is a monoclonal antibody that binds to HER2/Neu, CD20, CTLA4, EGFR1; paragraph [0012]), and said immunomodulatory moiety comprises an amino acid sequence of the extracellular domain of transforming growth factor-beta receptor II (TGFbetaRII) (specifically the immunomodulatory moiety includes an extracellular ligand-binding domain of Transforming growth factor-beta receptor TGF- RII; paragraph [0016]). They further disclose Biocon further discloses wherein said targeting
moiety is an antibody specifically binds epidermal growth factor receptor (EGFR) (the tumor targeting moiety is a monoclonal antibody that binds to HER2/Neu, CD20, CTLA4, EGFR1 and wherein the antibody can be the full antibody, heavy chain or light chain; paragraph [0012]) that comprises a heavy chain that comprises an amino acid sequence at least 95%, 96%. 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 43 (a heavy chain comprising SEQ ID NO: 43, where SEQ ID NO: 43 of the instant application is 100% identical to SEQ ID NO: 5, paragraph [0046]), and a light chain that comprises an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 44 (a light chain comprising SEQ ID NO: 44, where SEQ ID NO: 44 of the Instant application is 100% identical to SEQ ID NO:15, paragraph [0046])15, and wherein said immunomodulatory moiety comprises an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 56 (a immunomodulatory moiety comprising SEQ ID NO: 56, where SEQ ID NO: 56 of the instant application is 100% identical to SEQ ID NO: 4, paragraph [0045], (see search result in PE2E). Govindappa et al. do not teach that the method further comprise to administer another antibody that comprises administering anti-PD1 antibody that specifically binds to PD1, wherein the antibody comprises a VH that comprises a VH CDR1, VH CDR2, and VH CDR3, wherein (i) the amino acid sequence of the VH CDR1 comprises the amino acid sequence of SEQ ID NO: 1;(ii) the amino acid sequence of the VH CDR2 comprises the amino acid sequence of SEQ ID NO: 2; and(iii) the amino acid sequence of the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 3; and a VL that comprises a VL CDR1, a VL CDR2, and a VL CDR3, wherein (i) the amino acid sequence of the VL CDR1 comprises the amino acid sequence of SEQ ID NO: 4;(ii) the amino acid sequence of the VL CDR2 comprises the amino acid sequence of SEQ ID NO: 5; and(iii) the amino acid sequence of the VL CDR3 comprises the amino acid sequence of SEQ ID NO: 6, and that the method is for treating head and neck squamous carcinoma.
Papadopoulos et al. teach treating cancer comprising anti-PD1 antibody or a functional fragment thereof, wherein the anti-PD1 antibody, or functional fragment specifically binds PD1 and it is a full-length antibody, a single chain variable fragment
(scFv), a scFv2, a scfv-Fc, a Fab, a Fab', a F(ab')2, or a F(v) (The antibodies of the invention can be full-length (for example, a Fab, F(ab)2 or scFv fragment); paragraph [0008]). The reference teaches treating cancer, wherein said cancer is squamous head and neck cancer (see paragraph [0003, 0052]). They teach a number of anti-PD1 antibodies are well described in the prior art (see paragraph [0006]) and the instantly claimed an antibody that specifically binds programmed cell death protein 1 (PD1) comprising a VH that comprises a VH CDR1, VH CDR2, and VH CDR3, wherein (i) the amino acid sequence of the VH CDR1 comprises the amino acid sequence of SEQ ID NO: 1;(ii) the amino acid sequence of the VH CDR2 comprises the amino acid sequence of SEQ ID NO: 2; and(iii) the amino acid sequence of the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 3; and a VL that comprises a VL CDR1, a VL CDR2, and a VL CDR3, wherein (i) the amino acid sequence of the VL CDR1 comprises the amino acid sequence of SEQ ID NO: 4;(ii) the amino acid sequence of the VL CDR2 comprises the amino acid sequence of SEQ ID NO: 5; and(iii) the amino acid sequence of the VL CDR3 comprises the amino acid sequence of SEQ ID NO: 6 are 100% identical to the Merk’s antibody pembrolizumab (see Search results in PE2E of 12/10/2025 and 3/4/2026). They do not teach that that monoclonal antibody is antibody Pembrolizumab. However, the specification discloses that pembrolizumab is well known in the art (Pembrolizumab is also known as KEYTRUDA, MK-3475, Merk3475, labrolizumab and SCH-900475 (US 20150190506, paragraph [0166]). US 20150190506 is applied to support the art and not applied as a prior art.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use an anti-PD1 antibody as taught by Papadopoulos et al. including Pembrolizumab in combination with a fusion protein that comprises a targeting moiety and an immunomodulatory moiety, wherein: i-the targeting moiety comprises an antibody that specifically binds epidermal growth factor receptor (EGFR) comprising a VH that comprises a VH CDR1, VH CDR2, and VH CDR3, wherein (i) the amino acid sequence of the VH CDR1 comprises the amino acid sequence of SEQ ID NO: 34;(ii) the amino acid sequence of the VH CDR2 comprises the amino acid sequence of SEQ ID NO: 35; and(iii) the amino acid sequence of the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 36; and a VL that comprises a VL CDR1, a VL CDR2, and a VL CDR3, wherein (i) the amino acid sequence of the VL CDR1 comprises the amino acid sequence of SEQ ID NO: 37;(ii) the amino acid sequence of the VL CDR2 comprises the amino acid sequence of SEQ ID NO: 38; and(iii) the amino acid sequence of the VL CDR3 comprises the amino acid sequence of SEQ ID NO: 39; and(ii) the immunomodulatory moiety comprises an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 56 as taught by Govindappa et al. Additionally, one would have been motivated to do so because Govindappa et al teach treating cancer using a fusion protein and Papadopoulos et al. also teach cancer using an anti-PD1 and that the combination of the two for cancer treatment would have been obvious to one skill in the art. Further, one would have a reasonable expectation of success in combination of an anti-PD1 antibody as well as a fusion protein having targeting moiety comprising an antibody that specifically binds epidermal growth factor receptor (EGFR) with TGFbRII are known for treating a cancer. Therefore, the instantly claimed invention would have been obvious to one ordinary skill in the art over the combined teachings of the prior art.
Claim(s) 104-107 is/are rejected under 35 U.S.C. 103 as being unpatentable over Govindappa et al. (IDS, US 2013/0287802) in view of Papadopoulos et al. (IDS, US 2020/0330794) as applied to claims 71-75, 80, 88, 89, 94, 103, and 114 -119 above, and further in view of Chatterjee et al. (IDS, US 5,977,316).
The instant invention is further drawn to a method of treating cancer in a human subject in need thereof comprising administering the subject: (a) an antibody
that specifically binds programmed cell death protein 1 (PD1) comprising a VH that comprises a VH CDR1, VH CDR2, and VH CDR3, comprising amino acid sequences of SEQ ID NOs: 1-3; and a VL that comprises a VL CDR1, a VL CDR2, and a VL CDR3, comprising amino acid sequences of SEQ ID NOs: 4-6; and (b) a fusion protein that comprises a targeting moiety and an immunomodulatory moiety, wherein: i-the targeting moiety comprises an antibody that specifically binds epidermal growth factor receptor (EGFR) comprising a VH that comprises VH CDR1, VH CDR2, and VH CDR3, having amino acid sequences of SEQ ID NOs: 34-36; and a VL that comprises a VL CDR1, a VL CDR2, and a VL CDR3, having the amino acid sequences of SEQ ID NOs: 37-39; and(ii) the immunomodulatory moiety comprises an amino acid sequence at least 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 56, wherein the immunomodulating moiety is indirectly fused to the targeting moiety via a peptide linker having amino acid sequence of SEQ ID NO: 57, wherein the immunomodulatory moiety is fused the C terminus of light chain or heavy chain.
The teachings of Govindappa et al. and Papadopoulos et al. are summarized above. Govindappa et al teach a fusion of antibody that specifically binds to EFGR and wherein the antibody can be the full antibody, heavy chain or light chain; paragraph [0012]), and wherein said immunomodulatory moiety is fused to the C terminus of said light chain of said targeting moiety (see paragraph [0038]). Neither Govindappa et al. nor Papadopoulos et al teach that the fusion is via a linker, wherein the linker comprises amino acid sequence of SEQ ID NO: 57, and wherein the fusion is C terminus of light chain or heavy chain of the immunomodulatory moiety.
Chatterjee teaches a peptide linker (encoded by a polynucleotide
molecule of claim 1), wherein said peptide linker is not from an antibody (claim 3); where the N-terminal of a polypeptide is linked to the C-terminal of the light chain (single chain variable region fragments are made by linking light and/or heavy chain variable regions by using a short linking peptide carboxy terminus of one variable region and the amino terminus of another variable region or any portion of the heavy or light chain can be used in any combination, the light chain variable region can be linked to the heavy chain variable region; linker comprising SEQ ID NO: 57, where SEQ ID NO: 57 of the instant application is 100% identical to SEQ ID NO. 45; column 24, lines 49-66).
Therefore, It would have been prima farcie obvious to a person of ordinary skill in the art, at the time of the invention, to have modified the method of claim 1, as previously disclosed by Govindappa et al. and Papadopoulos et al., to include a linker, as disclosed by Chatterjee, for the benefit of a superior method that is able to link the fusion protein, and provide support (see column 24, lines 49-62). Additionally, one would have been motivated to do so because teach that fusion protein with can be in any order of VH or VL using a linker of (GGGGS)3 which is 100% identical to the instant linker (see col. 25, lines 8+). Further, one would have a reasonable expectation of success in using a linker to attach a polypeptide of SEQ ID NO: 56 with the C terminal of VH or VL of an antibody that specifically binds EGFR because making a fusion protein via a linker is routine in the art. Therefore, the instantly claimed invention would have been obvious to one ordinary skill in the art over the combined teachings of the prior art.
Conclusion
No claim is allowed.
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/GYAN CHANDRA/Primary Examiner, Art Unit 1674
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