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 .
Claims 1-13 are under consideration in the instant Office Action.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code, see page 15 of the instant specification. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
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 5-7 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.
Instant claims 5-7 recite the heavy and light chain variable region sequences of the claimed antibody as “… an amino acid sequence of SEQ ID NO:…” It is unclear what is meant by “an amino acid sequence of SEQ ID NO:…” as the use of “an amino acid” broadens the scope of the claim as it does not explicitly define all embodiments of the sequence. For example, this terminology of “an amino acid” can be interpreted as a subset of amino acids contained within the listed sequence identity number or read on the full length of the protein sequence as long as it includes the amino acids set forth in the sequence. Applicant is encouraged to amend the claim language to read as “…comprising SEQ ID NO:…” or “…comprising the amino acid sequence of SEQ ID NO:…” at every iteration to obviate this rejection.
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.
Claims 1-5 and 11-13 are rejected under 35 U.S.C. 103 as being unpatentable over Pardridge et al. (US 2007/0081992 A1, IDS, 5/30/204) and Sawyer et al., WO2017/053794 (IDS, IDS, 5/30/204), in view of Khare (US 2009/0226435 A1, IDS, 5/30/204) and Zhang et al. (US 2012/0195831 A1, IDS, 5/30/204).
Pardridge teaches and claims a recombinant fusion protein comprising “neuregulin” fused to a monoclonal antibody (mAb) backbone (see Pardridge’s claims 16 and 22, for example), thus meeting the limitations of claim 1. Note that Pardridge’s “neuregulin” is equivalent to “neuregulin-1” in the instant claims as evidenced by the instant specification at p.1, [0003], which states, “Neuregulin (NRG; heregulin, HRG), also known as glial growth factor (GGF) and new differentiation factor (NDF), is a type of glycoprotein with a molecular weight of 44 KD” and evidenced by the Wikipedia entry “Neuregulin 1”, retrieved from https://en.wikipedia.org/wiki/Neuregulin_1 on 03/27/2020 (IDS, 5/30/204, #199), which states that that same protein is called Neuregulin-1, see paragraph under the heading “Structure”. Pardridge’s fusion protein comprising full-length NRG-1 meets the limitations of claims 1-2 and 5 because full-length NRG-1 comprises a fragment of the cardioprotective protein neuregulin-1 (NRG-1), wherein the fragment comprises an active fragment and the active domain of NRG-1. Pardridge fails to teach that the monoclonal antibody is monospecific for ErbB3 (HER3), as in claim 1.
Sawyer teaches NRG-1 fragments that are cardioprotective (see abstract, [003],[0049-0050]). Sawyer teaches these NRG1 fragments to include SEQ ID NO:11 (see page 58) which is the same as the instant SEQ ID NO:4 of instant claim 5. Sawyer does not teach that the constructs comprise HER3.
Khare teaches fusion proteins comprising tumor targeting moieties including an antibody to HER3 (see e.g. [0035]) as in instant claim 1. Khare teaches fusion of N or C terminus of the antibody heavy or light chain with the target peptides (see [0041]) as in instant claim 1. Khare teaches genetically engineered fusion molecules with linkers and teach SEQ ID NO: 26 (see [0033]) as a linker which is the same as instant SEQ ID NO: 5 of instant claims 2-3. Khare teaches the Fc regions which is used to define the C-terminal region of an immunoglobulin heavy chain (see [0028]) as in instant claim 4. Khare teaches methods of producing fusion molecules with steps comprising 1) preparing/obtaining targeting moiety; 2) preparing/obtaining a costimulatory molecule and/or a chemokine and/or cytokine; 3) preparing/obtaining a linker; 4) attaching 1) to 2) using said linker to prepare a fusion molecule; and 5) purifying said fusion molecule (see [0042] and [0061]). Khare teaches that the invention uses expression vectors for eukaryotic organisms and Chinese hamster ovary cells (CHO), (see [0043-0044]) as required in instant claims 1 and 11-13. Khare fails to teach that the anti-HER3 antibody is a monoclonal antibody monospecific to HER3.
Zhang teaches monoclonal antibodies, which are monospecific for HER3 and the use of said antibodies in fusion protein constructs (see e.g. [0026], [0045], and [0046]). Zhang does not teach that the constructs comprise NRG-1.
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of Pardridge, Sawyer, Khare and Zhang. The person of ordinary skill in the art would have been motivated to make and use the invention as claimed because Pardridge, Khare and Zhang teach recombinant fusion proteins comprising monoclonal antibodies for treatment of cancers, wherein Pardridge teaches that one can include NRG-1 (see claim 16) and a tumor targeting molecule (see [0150] and [0227]), while Sawyer teaches that the claimed fragment had been previous identified in the art, Khare teaches that such as tumor targeting molecule is an antibody to HER3 (see [0002] and [0035]) and Zhang teaches specific examples a monoclonal antibodies monospecific for HER3 suitable for use in Pardridge’s and Khare’s fusion proteins (see e.g. [0024]-[0027]). One of ordinary skill in the art would be motivated to use the methods of production taught by Khare with a reasonable expectation of success in being capable of using the disclosed method by Khare to produce the required fusion protein. The person of ordinary skill in the art would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references.
Claims 1-8 and 11-13 are rejected under 35 U.S.C. 103 as being unpatentable over Pardridge et al. (US 2007/0081992 A1, IDS, 5/30/204), Sawyer et al., WO2017/053794 (IDS, IDS, 5/30/204), Khare (US 2009/0226435 A1, IDS, 5/30/204) and Zhang et al. (US 2012/0195831 A1, IDS, 5/30/204) as applied to claims 1-5 and 11-13 above, and further in view of Hettmann et al. US2017/002131 (instant PTO-892).
None of the references above teach the required sequences of instant claims 6-8.
Hettmann teaches that the ligand Heregulin (HRG) binds to the extracellular domain of HER3 and activates the receptor-mediated signaling pathway by promoting dimerization with other human epidermal growth factor receptor (HER) family members and transphosphorylation of its intracellular domain (see [0009]). Hettmann teaches an antibody conjugate that encompasses an anti-HER3 antibody with a linker to a compound (see [0053]). Hettmann teaches methods of obtaining monoclonal antibodies which include HER3 antibodies (see [0129], [0138-147]). Hettmann teaches that the antibody drug conjugate comprises the antibody disclosed in SEQ ID NOs: 583 and 584 in the heavy and light chain, respectively (see their claim 12) and are the same sequences of SEQ ID NOs: 2 and 3 of the instant claims 6-8. Hettmann does not teach the NRG-1 fragment of instant claim 1 and SEQ ID NO: 14 of claim 8.
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of Pardridge, Sawyer, Khare, Zhang and Hettmann. The person of ordinary skill in the art would have been motivated to make and use the invention as claimed because Pardridge, Khare and Zhang teach recombinant fusion proteins comprising monoclonal antibodies for treatment of cancers, wherein Pardridge teaches that one can include NRG-1 (see claim 16) and Sawyer teaches that instant fragment of SEQ ID NO:4 of instant claim 5. One of ordinary skill in the art would be motivated to use the specific anti-HER3 taught by Hettmann to produce the instantly claimed NRG1 fusion protein to anti-HER3 antibody which is found in instant SEQ ID NO: 14 with a reasonable expectation of success since Hettmann already teaches using this specific monoclonal anti-HER3 antibody in a product that used a linker to conjugate other products to the antibody. Therefore, one of ordinary skill in the art would be capable of using disclosed production methods as taught Khare and Hettmann to produce the instantly claimed fusion product with a reasonable expectation of success.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-35 of U.S. Patent No. 11,718,652 in view of Khare (US 2009/0226435 A1, IDS, 5/30/204). ‘652 claims methods that use the product that is produced in the method of the instant claims. ‘652 claims NRG-1 fusion protein with HER3 monoclonal antibodies that required the same SEQ ID NOs: 2, 3, 4, 5, 6, 7, 8 and 14. The ‘652 does not claim a method of producing the recombinant fusion protein comprising a fragment of the protein neuregulin-1 (NRG-1) fused to a monospecific ErbB3 (HER3) monoclonal antibody (mAb). Khare teaches methods for producing fusion proteins. Khare teaches fusion proteins comprising tumor targeting moieties including an antibody to HER3 (see e.g. [0035]) as in instant claim 1. Khare teaches fusion of N or C terminus of the antibody heavy or light chain with the target peptides (see [0041]) as in instant claim 1. Khare teaches genetically engineered fusion molecules with linkers and teach SEQ ID NO: 26 (see [0033]) as a linker which is the same as instant SEQ ID NO: 5 of instant claims 2-3. Khare teaches the Fc regions which is used to define the C-terminal region of an immunoglobulin heavy chain (see [0028]) as in instant claim 4. Khare teaches methods of producing fusion molecules with steps comprising 1) preparing/obtaining targeting moiety; 2) preparing/obtaining a costimulatory molecule and/or a chemokine and/or cytokine; 3) preparing/obtaining a linker; 4) attaching 1) to 2) using said linker to prepare a fusion molecule; and 5) purifying said fusion molecule (see [0042] and [0061]). Khare teaches that the invention uses expression vectors for eukaryotic organisms and Chinese hamster ovary cells (CHO), (see [0043-0044]) as required in instant claims 1 and 11-13. Khare fails to teach that the anti-HER3 antibody is a monoclonal antibody monospecific to HER3. Therefore, one of ordinary skill in the art would be motivated to use the methods taught Khare to produce the method of manufacturing the fusion protein of ‘652 with a reasonable expectation of success.
Claims 1-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-38 of U.S. Patent No.11,046,741 in view of Khare (US 2009/0226435 A1, IDS, 5/30/204). ‘741 claims the product that is produced in the method of the instant claims. ‘741 claims NRG-1 fusion protein with HER3 monoclonal antibodies that required the same SEQ ID NOs: 2, 3, 4, 5, 6, 7, 8 and 14. The ‘741 does not claim a method of producing the recombinant fusion protein comprising a fragment of the protein neuregulin-1 (NRG-1) fused to a monospecific ErbB3 (HER3) monoclonal antibody (mAb). Khare teaches methods for producing fusion proteins. Khare teaches fusion proteins comprising tumor targeting moieties including an antibody to HER3 (see e.g. [0035]) as in instant claim 1. Khare teaches fusion of N or C terminus of the antibody heavy or light chain with the target peptides (see [0041]) as in instant claim 1. Khare teaches genetically engineered fusion molecules with linkers and teach SEQ ID NO: 26 (see [0033]) as a linker which is the same as instant SEQ ID NO: 5 of instant claims 2-3. Khare teaches the Fc regions which is used to define the C-terminal region of an immunoglobulin heavy chain (see [0028]) as in instant claim 4. Khare teaches methods of producing fusion molecules with steps comprising 1) preparing/obtaining targeting moiety; 2) preparing/obtaining a costimulatory molecule and/or a chemokine and/or cytokine; 3) preparing/obtaining a linker; 4) attaching 1) to 2) using said linker to prepare a fusion molecule; and 5) purifying said fusion molecule (see [0042] and [0061]). Khare teaches that the invention uses expression vectors for eukaryotic organisms and Chinese hamster ovary cells (CHO), (see [0043-0044]) as required in instant claims 1 and 11-13. Khare fails to teach that the anti-HER3 antibody is a monoclonal antibody monospecific to HER3. Therefore, one of ordinary skill in the art would be motivated to use the methods taught Khare to produce the method of manufacturing the fusion protein of ‘741 with a reasonable expectation of success.
Conclusion
No claims are allowed.
Advisory Information
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/AURORA M FONTAINHAS/Primary Examiner, Art Unit 1675