Office Action 2: Notice of Allowance (2025-01-29)

CLAIMS:
Amendments to the Claims

Please amend claims 1 and 2 as shown in the listing of claims.Please cancel claims 3-8.Please add new claims 9-15.This listing of claims will replace all prior versions, and listings of claims in the application.

Listing of Claims:

Filed: September 12, 2024

1\. (Currently Amended) An isolated molecule comprising :
(a) a targeting moiety comprising \[\[es\]\] an antibody\[\[,\]\] or antibody fragment thereof, comprising amino acids 1-119 of SEQ ID NO: 2 and the amino acid\[\[s\]\] sequence of SEQ ID NO: 71, which specifically binds Epidermal Growth Factor Receptor (EGFR}; and
(b) an immunomodulatory moiety comprising \[\[es\]\] an amino acid sequence of the extracellular domain of Transforming growth factor-beta receptor II (TGF-PRII) comprising the amino acid sequence of SEQ ID NO: 87.

2\. (Currently Amended) The molecule of claim 1, wherein the targeting moiety comprises an antibody fragment selected from a Fab\[\[,\]\] or scFv .

3-8. (Canceled)47

9\. (New) The molecule of claim 2, wherein the antibody fragment comprises a light chain domain or a variable heavy chain domain.

10\. (New) The molecule of claim 9, wherein the antibody fragment comprises a light chain domain comprising the amino acid sequence of SEQ ID NO: 71.

11\. (New) The molecule of claim 10, further comprising a polypeptide linker comprising the amino acid sequence of SEQ ID NO: 104.

12\. (New) The molecule of claim 11, wherein the light chain domain comprising the amino acid sequence of SEQ ID NO: 71 is fused to an N-terminus of the polypeptide linker comprising the amino acid sequence of SEQ ID NO: 104.

13\. (New) The molecule of claim 12, wherein the immunomodulatory moiety comprising the amino acid sequence of SEQ ID NO: 87 is fused to a C-terminus of the polypeptide linker comprising the amino acid sequence of SEQ ID NO: 104.

14\. (New) The molecule of claim 9, wherein the variable heavy chain domain comprises amino acids 1-119 of SEQ ID NO: 2.

15\. (New) An isolated molecule comprising:
(a) a targeting moiety comprising an antibody fragment which specifically binds Epidermal Growth Factor Receptor (EGFR) comprising a light chain domain comprising the amino acid sequence of SEQ ID NO: 71 and a variable heavy chain domain comprising amino acids 1-119 of SEQ ID NO: 2;
(b) an immunomodulatory moiety comprising an amino acid sequence of the extracellular domain of Transforming growth factor-beta receptor II (TGF-3RII) comprising the amino acid sequence of SEQ ID NO: 87; and
(c) a polypeptide linker comprising the amino acid sequence of SEQ ID NO: 104;
wherein the light chain domain comprising the amino acid sequence of SEQ ID NO: 71 is fused to an N-terminus of the polypeptide linker comprising the amino acid of SEQ ID NO: 104, and

Filed: September 12, 2024 Page 4 wherein the immunomodulatory moiety comprising the amino acid sequence of SEQ ID NO: 87 is fused to a C-terminus of the polypeptide linker comprising the amino acid sequence of SEQ ID NO: 104.

OFFICE ACTION:
DETAILED ACTION
Notice of Pre-AIA  or AIA  Status
The present application is being examined under the pre-AIA  first to invent provisions.
Status of Application, Amendments and/or Claims
The amendment of 23 December 2024 has been entered in full.  Claims 1 and 2 are amended. Claims 3-8 are cancelled. Claims 9-15 are added.
Claims 1, 2, and 9-15 are under consideration in the instant application.
Withdrawn Objections and/or Rejections
1.	The objections to claims 1 and 2 as set forth at page 6 of the previous Office Action of 03 December 2024 are withdrawn in view of the amended claims (23 December 2024).
2.	The rejection of claims 2 and 3 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as set forth at pages 6-7 of the previous Office Action of 03 December 2024 is withdrawn in view of amended claim 2 and cancelled claim 3 (23 December 2024).
3.	The rejection of claims 1-3 on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 9,441,044 as set forth at pages 9-10 of the previous Office Action of 03 December 2024 is withdrawn in view of the submission of a terminal disclaimer (23 December 2024).
4.	The provisional rejection of claims 1-3 on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of copending Application No. 18/811,627 in view of Huang et al. (App Environ Microbiol 72(12): 7748-7759, 2006) as set forth at pages 10-14 of the previous Office Action of 03 December 2024 is withdrawn in view of the submission of a terminal disclaimer (23 December 2024).
Conclusion
Claims 1, 2, and 9-15 are allowed.

APPLICANT REBUTTAL: REMARKS
Prior to this Communication, claims 1-9 were pending. With the present communication, claims 1 and 2 have been amended, claims 3-8 have been canceled without prejudice or disclaimer and new claims 9-15 have been added. Support for the claim amendments and new claims may be found generally throughout the application and claims as originally filed. No new matter is added. After entry of the amendments, claims 1-2 and 9-15 will be pending and under consideration.
Examiner's Interview
Applicant thanks Examiner Bunner for the telephone interview with Applicant's representatives on December 17, 2024. During the interview, proposed claim amendments were discussed to address clarity and indefiniteness rejections and the submission of a terminal disclaimer to address the obviousness type double patenting rejection were discussed. The Examiner stated that the proposed amendments and filing of a terminal disclaimer were reasonable to overcome the objections/rejections, but that such would be considered once the response is made of record.
Election/Restriction
The Examiner contacted Applicant's representative regarding a telephonic restriction requirement. The Examiner restricted the claims into two groups:
I. Claims 1-3 drawn to an isolated molecule comprising a targeting moiety fused
with an immunomodulatory moiety, wherein the targeting moiety comprises an antibody, scFv, or Fe-containing polypeptide that targets EGFR; and the immunomodulatory moiety comprises an amino acid sequence of extracellular
domain of TGF-BRII; and
II. Claims 4-8 drawn to a method of treating cancer in a subject in need thereof
comprising administering a therapeutically effective amount of a molecule comprising a targeting moiety fused with an immunomodulatory moiety,
wherein the targeting moiety comprises an antibody, scFv, or Fc-containing polypeptide that targets EGFR; and the immunomodulatory moiety comprises
an amino acid sequence of extracellular domain of TGF-BRII.
During a telephone conversion with Applicant's representative on November 22, 2024, a provisional election to pursue the invention of Group I, claims 1-3, without traverse was made. Applicant affirms the election of Group I, claims 1-3 without traverse.
Applicant reserves the right to pursue prosecution of non-elected subject matter and/or species upon an indication of allowance of any generic claims and to request rejoinder in the present application or in a later filed application claiming the benefit of priority of the above- identified application.
Claim Objections
The Examiner objected to claim 1 stating that the acronym "EGFR" is recited without first defining what it represents.
Applicant amended claim 1 to define "EGFR" as Epidermal Growth Factor Receptor". submits that this amendment renders the objection moot and respectfully requests withdrawal of the objection.
The Examiner objected to claim 2 not reciting a sequence identifier for the amino acid sequence of the linker and suggested that the claim be amended to recite "... linker comprising the amino acid sequence of SEQ ID NO: 104."
Applicant amended claim 2 to recite "wherein the targeting moiety comprises an antibody fragment selected from a Fab or scFv." Applicant submits that these amendments render the objection moot and respectfully request withdrawal of the objection.
Rejections under 35 USC
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Claims 2 and 3 stand rejected under 35 USC § 112, second paragraph as being indefinite for failing to particularly point out and distinctly claim the subject matter of the invention. Applicant respectfully traverses this rejection.
The Examiner states that claims 2 and 3 are indefinite because the elements comprising the isolated molecule are unclear, as well as the structure of the molecule.
As an initial matter, claim is canceled. Applicant amended claim 2 to recite "wherein the targeting moiety comprises an antibody fragment selected from a Fab or scFv." Applicant submits that these amendments and cancelations render the rejection moot and respectfully requests reconsideration and withdraw of the rejection.
Double Patenting Re
j
ection
Claims 1-3 are provisionally rejected on the ground of non-statutory obviousness-type double patenting over claims 1-9 of U.S. Patent No. 9,441,044. Applicants respectfully traverse this rejection.
Without acquiescing to the Examiner's assertion and to expedite prosecution of the claimed invention, a terminal disclaimer is hereby submitted together with this paper to overcome the non-statutory obviousness-type double patenting rejections over U.S. Patent No. 9,441,044. Accordingly, withdrawal of the double patenting rejection is respectfully requested.
Claims 1-3 are provisionally rejected on the ground of non-statutory obviousness-type double patenting over claims 1-12 of U.S. Patent Appl. Serial No. 18/811,627 in view of Huang et al. (App Environ Microbiol 72(12):7748-7759, 2006). Applicants respectfully traverse this rejection.
Without acquiescing to the Examiner's assertion and to expedite prosecution of the claimed invention, a terminal disclaimer is hereby submitted together with this paper to overcome the non-statutory obviousness-type double patenting rejections over U.S. Patent Appl. Serial No. 18/811,627. Accordingly, withdrawal of the double patenting rejection is respectfully requested.
CONCLUSION


CITED REFERENCE SUMMARIES: Ref US9441044: Claims:
1. An isolated molecule comprising a targeting moiety fused with an immunomodulatory moiety, wherein:
(a) the targeting moiety specifically binds Epidermal Growth Factor Receptor (EGFR); and
(b) the immunomodulatory moiety comprises an amino acid sequence of the extracellular domain of Transforming growth factor-beta receptor II (TGF-βRII).
2. The molecule of claim 1, wherein the targeting moiety comprises an antibody, antibody fragment, scFv, or Fc-containing polypeptide that specifically binds EGFR or a fragment thereof.
3. The molecule of claim 1, wherein the immunomodulatory moiety comprises an amino acid sequence of the extracellular domain of Transforming growth factor-beta receptor selected from the group consisting of SEQ ID NO: 79-91.
4. The molecule of claim 3, wherein the immunomodulatory moiety comprises the amino acid sequence corresponding to SEQ ID NO: 87 or a binding fragment thereof.
5. The molecule of claim 4, wherein the molecule comprises the amino acid sequence corresponding to SEQ ID NO: 2 or a binding fragment thereof.
6. The molecule of claim 5, wherein the molecule comprises the amino acid sequence corresponding to SEQ ID NO: 2 or a binding fragment thereof and the amino acid sequence corresponding to SEQ ID NO: 71 or a binding fragment thereof.
7. The isolated molecule of claim 1, further comprising a linker at the CH3 region of the Fc.
8. The isolated molecule of claim 7, wherein the linker is (GGGGS)n (SEQ ID NO:104)n and wherein n is 1, 2, 3, 4, 5, 6, 7 or 8.
9. The isolated molecule of claim 7, wherein the linker comprises the amino acid sequence GGGGSGGGGSGGGGS (SEQ ID NO:104).
10. An isolated molecule comprising a targeting moiety fused with an immunomodulatory moiety, wherein:
(a) the targeting moiety specifically binds Epidermal Growth Factor Receptor (EGFR); and
(b) the immunomodulatory moiety comprises an amino acid sequence of the extracellular domain of Transforming growth factor-beta receptor (TGF-βR).
Ref APP-18_811627: Claims:
A method of treating a subject having cancer, comprising: administering to the subject therapeutically effective amounts of (a) a fusion protein comprising a targeting moiety fused to an immunomodulatory moiety, wherein: (i) the targeting moiety comprises amino acids 1-119 of SEQ ID NO: 225 and amino acids 1-107 of SEQ ID NO: 226, and (ii) the immunomodulatory moiety comprises a ligand binding fragment of the extracellular domain (ecd) of transforming growth factor β receptor II (TGFβRIIecd) having the amino acid sequence of SEQ ID NO: 6, and (b) pembrolizumab.
administering to the subject therapeutically effective amounts of
(a) a fusion protein comprising a targeting moiety fused to an immunomodulatory moiety, wherein: (i) the targeting moiety comprises amino acids 1-119 of SEQ ID NO: 225 and amino acids 1-107 of SEQ ID NO: 226, and (ii) the immunomodulatory moiety comprises a ligand binding fragment of the extracellular domain (ecd) of transforming growth factor β receptor II (TGFβRIIecd) having the amino acid sequence of SEQ ID NO: 6,
(i) the targeting moiety comprises amino acids 1-119 of SEQ ID NO: 225 and amino acids 1-107 of SEQ ID NO: 226, and
(ii) the immunomodulatory moiety comprises a ligand binding fragment of the extracellular domain (ecd) of transforming growth factor β receptor II (TGFβRIIecd) having the amino acid sequence of SEQ ID NO: 6,
The method of claim 1, wherein the targeting moiety of said fusion protein is an antibody and the immunomodulatory moiety is fused to the C terminus of the heavy chain of the antibody.
The method of claim 1, wherein the targeting moiety of said fusion protein is an antibody and the immunomodulatory moiety is fused to the C terminus of the light chain of the antibody.
The method of claim 3, wherein the fusion protein further comprises a polypeptide linker fused between the targeting moiety and the immunomodulatory moiety.
The method of claim 4, wherein the linker has the amino acid sequence of SEQ ID NO: 4.
The method of claim 5, wherein the fusion protein comprises, from N-terminus to C-terminus, a light chain comprising SEQ ID NO: 75, fused to a linker comprising SEQ ID NO: 4, fused to the TGFβRIIecd comprising SEQ ID NO: 6.
The method of claim 1, wherein the subject is administered said fusion protein prior to, simultaneously with, or following administration of pembrolizumab.
The method of claim 1, wherein said fusion protein is administered by intravenous administration.
The method of claim 1, wherein pembrolizumab is administered by intravenous or subcutaneous administration.
The method of claim 1, wherein the cancer is head and neck cancer (HNSCC).
The method of claim 1, wherein amino acids 1-119 of SEQ ID NO: 225 comprise the VH domain of cetuximab.
The method of claim 1, wherein amino acids 1-107 of SEQ ID NO: 226 comprise the VL domain of cetuximab.