DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Response to Amendment
Applicant’s preliminary amendment filed 22 May 2024 has been received and entered. Claims 1-62 have been canceled and claims 63-85 have been added. Claims 63-85 are currently pending and 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.
The information disclosure statement (IDS) submitted on 03 April 2024 has been considered by the examiner.
Drawings
The drawings were received on 22 May 2024. These drawings are not acceptable.
The drawings are objected to because they do not comply with 37 CFR 1.84(a)(1) and 1.84(l). Both of these sections of 37 CFR 1.84 require the use of solid, black lines. The drawings which have been submitted do not have solid black lines (see screenshot below).
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It is noted that a supplemental drawing file was provided (22 May 2024). However, the same type of file was presented in the most recent parent application (16/593,750) and the patent issued with drawings that did not have solid black lines. Therefore, this submission of a file does not correct the noted issue.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," 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 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) 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 of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is defective. See item 1) a) or 1) b) above.
Applicant’s filing of a substitute specification to include an incorporation statement, filed 22 May 2024, has been entered. However, the file name in the specification does not match the file name in the PTO system. See screenshots below:
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Specifically, the file name in the specification uses a lowercase “L” while the actual file name uses a capital “L”. Because the file name must be identical, correction is required. A substitute specification must be filed to make the correction.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specification
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed. The current claims are directed to methods of treating ocular disorders by administration of a VEGFR-3 ligand binding molecule and a VEGF-A inhibitor.
Applicant is reminded of the proper content of an abstract of the disclosure.
A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art.
If the patent is of a basic nature, the entire technical disclosure may be new in the art, and the abstract should be directed to the entire disclosure. If the patent is in the nature of an improvement in an old apparatus, process, product, or composition, the abstract should include the technical disclosure of the improvement. The abstract should also mention by way of example any preferred modifications or alternatives.
Where applicable, the abstract should include the following: (1) if a machine or apparatus, its organization and operation; (2) if an article, its method of making; (3) if a chemical compound, its identity and use; (4) if a mixture, its ingredients; (5) if a process, the steps.
Extensive mechanical and design details of an apparatus should not be included in the abstract. The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words in length.
See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts.
The abstract of the disclosure is objected to because it contains no information regarding that which is new in the art to which the invention pertains. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
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 63-85 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-44 of U.S. Patent No. 9,745,558 or claims 1-19 of U.S. Pat. No. 11,866,739 and in view of Patel et al. (WO2010127029A1) and Hohman (US2013/0296238A1).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims and the claims of the issued US Patent are both drawn to a method of treating a subject having an ocular disorder associated with neovascularization, the method comprising administering a composition comprising a purified or isolated, soluble, ligand binding polypeptide or ligand polypeptide comprising an amino acid sequence having at least 95% identity to the sequence of amino acids defined by positions 47-115 of SEQ ID NO: 2, with the proviso that positions of the polypeptide corresponding to positions 104-106 of SEQ ID NO: 2 are not identical to N-X-S or N-X-T, wherein the polypeptide binds to at least one ligand polypeptide selected from human VEGF-C, VEGF-D, and PIGF, and a pharmaceutically acceptably diluent, adjuvant, excipient, or carrier. The instant claims recite that the ligand binding polypeptide comprises an amino acid sequence having at least 95% identity to the sequence of amino acids defined by positions 25-210 of SEQ ID NO:2, so it comprises more of SEQ ID NO:2 but does comprise the same region as that of ‘558.
The instant claims further comprise administering a composition comprising a VEGF-A inhibitor product and a pharmaceutically acceptable diluent, adjuvant, excipient, or carrier wherein the two compositions are administered in amounts effective to inhibit neovascularization, vascular endothelial cell proliferation
Before the effective filing date of the claimed invention, it was well known to treatment ocular disorders associated with neovascularization, such as diabetic macular edema (DME), with an inhibitor of VEGF-A. The prior art teaches that such treatments “suffer from two significant shortcomings: they are not effective in all patients, and they must be dosed frequently (at least every four to eight weeks) by a method of administration which many patients find disagreeable.” (Hohman, at [0005]). To address the shortcomings of a VEGF-A inhibitors as a monotherapy, Hohman discloses a method comprising administering to a patient in need of such treatment an inhibitor of VEGFR-2 activation, wherein the compounds of Hohman bind VEGF-B, VEGF-C, VEGF-D, PIGF or PDGF. Hohman further teach wherein the treated patient is refractory to treatment with an inhibitor of VEGF-A, including ranibizumab, bevacizumab, aflibercept, or pegaptanib therapy for age-related macular degeneration, diabetic macular edema, pathological myopia, branch retinal vein occlusion, or central retinal vem occlusion in a patient.
Although Hohman does not disclose the precise compounds recited in the instant claims, it is noted that the compounds of Hohman function in a similar manner as those compounds set forth in the instant claims. For example, the specification as filed teaches that the compounds of the present invention function to inhibit binding of VEGF-C and/or VEGF-D from binding to and stimulating VEGF-2 and/or VEGFR-3, see [00108]. The claims also state that the compounds of the instant invention bind to at least one ligand polypeptide selected from human. VEGF-C, VEGF-D, or PIGF.
Thus, it would have been obvious to a person of ordinary skill in the art, before the effective filing date of the instant invention, to have modified the claims issued in US Patent 9,745,558, to further comprise an additional step of administering to the subject a composition comprising a VEGF-A inhibitor product and a pharmaceutically acceptable diluent, adjuvant, excipient or carrier, wherein the compositions are in amounts effective to inhibit neovascularization, vascular endothelial cell proliferation, vascular permeability, edema, or inflammation in the subject.
Furthermore, the combination of multiple inhibitors of VEGF-signaling for treating eye diseases was known in the prior art as of the effective filing date of the instant invention. Patel et al. (WO2010127029A1) teach treatment of ophthalmological diseases by means of administering VEGF antagonist to an individual.
refractory to treatment with an inhibitor of VEGF-A, including ranibizumab, bevacizumab, ophthalmological diseases by means of administering VEGF antagonist to an individual. Moreover, Patel et al. defines “VEGF” in the following manner: [0095] “The term "VEGF" refers to a vascular endothelial growth factor that induces angiogenesis or an angiogenic process. As used herein, the term "VEGF" includes the various subtypes of VEGF (also known as vascular permeability factor (VPF) and VEGF-A) (see Figure 2(A) and (B)) that arise by, e.g., alternative splicing of the VEGF- A/VPF gene including VEGF.sub.121, VEGF.sub.165 and VEGF.sub. 189.
Further, as used herein, the term "VEGF" includes VEGF-related angiogenic factors such as PIGF (placenta growth factor), VEGF-B, VEGF-C, VEGF-D and VEGF-E, which act through a cognate VEFG receptor (i.e., VEGFR) to induce angiogenesis or an angiogenic process.”
Moreover, Patel et al. states that: [0097] the term "VEGF antagonist" refers to an agent that reduces, or inhibits, either partially or fully, the activity or production of a VEGF.
In one embodiment, Patel et al. teach that inhibitors of VEGF-signaling, such as VEGF receptor-Fc fusion protein, aflibercept and bevacizumab are useful in treating eye disease related conditions (reads on claims 82-90). See claim 1 of this reference:
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As stated above, it would have been obvious to a person of ordinary skill in the art at the effective filing date of the instant invention to have modified the methods set forth in the issued claims of U.S. Pat. No. 9,745,558 or U.S. Pat. No. 11,866,739 to combine an inhibitor of VEGF-C and/or VEGF-D with an inhibitor of VEGF-A in the treatment of ocular disease. One of ordinary skill in the art would have been motivated to make this modification of the patented method of treating an ocular disorder, because the prior art teaches that inhibitors of VEGF-A are also useful for treating ocular disorders, the same purpose as inhibitors of VEGF-C and/or VEGF-D. According to MPEP 2144.06, “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.).
Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Moffat et al. Inhibition of Vascular Endothelial Growth Factor (VEGF)-A Causes a Paradoxical Increase in Tumor Blood Flow and Up-Regulation of VEGF-D. Clin. Cancer Res. (2006); 12(5): 1525-1532.
Ikeda et al. The regulation of vascular endothelial growth factors (VEGF-A, -C, and -D) expression in the retinal pigment epithelium. Experimental Eye Research (2006); 83: 1031-1040.
Tammela et al. Blocking VEGFR-3 suppresses angiogenic sprouting and vascular network formation. Nature (2008); 454: 656-663.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Christine J Saoud whose telephone number is (571)272-0891. The examiner can normally be reached M-F, 8am-4pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Vanessa Ford can be reached at 571-272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Christine J Saoud/Primary Examiner, Art Unit 1645