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 1-17 are pending and under consideration.
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 6, and 14-16 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.
Claim 6 contains the trademark/trade name Susvimo®. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a VEGF inhibitor and, accordingly, the identification/description is indefinite.
The term “regulates” in claim 14 is a relative term which renders the claim indefinite. The term “regulates” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Dependent Claims 15-16 are also included in this rejection because the term “regulates” remains undefined.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 7-17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by KR20200040407A (‘407, published April, 2020, IDS)
As to claims 7-8, and 11-12 ‘407 teaches (see claims) methods of administering an antibody, nucleic acids encoding the antibody, or vectors containing the nucleic acid to a subject in need thereof wherein the antibody comprises the CDRs of SEQ ID Nos: 1-6 and comprises a light-chain variable region of SEQ ID NO:7 and a heavy-chain variable region of SEQ ID NO:8. See result set below. The antibody of the prior art is referenced as “2G4”- see Figures 6-7. 2G4 inhibits angiogenesis and targets c-KIT. Further, the current specification teaches (page 27, line 15) that the 2G4 antibody is an exemplary embodiment. Since the product of the prior art is the same as claimed, the in vivo administration of the antibody for therapeutic purposes would naturally inhibit the expression or activity of HIF-1α.
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As to claims 9-10, ‘407 teaches (see claims) that the antibody can be administered as a pharmaceutical composition to treat melanoma of the “eye”. Other diseases include treating vascular diseases such as diabetic retinopathy, macular degeneration, senile macular degeneration, glaucoma, glaucoma retinitis pigmentosa, choroidal neovascularization, immature retinopathy, corneal dystrophy, and retinal interlayer separation. Thus, inhibition of HIF-1α would encompass such tissues as the choroid or retina. This would also include cells selected from the group consisting of optic neurons, retinal Mueller cells, choroidal cells, retinal microvascular endothelial cells (RMECs), retinal pigment epithelial (RPE) cells and photoreceptor cells depending upon the route of administration such as eye drops or intravitreal injection.
As to claims 13-17, drawn to in vivo effects of administering the antibody, such as - inhibition is achieved through SCF/C-kit-induced phosphorylation (Claim 13) or regulation of angiogenic factors or inflammatory factors (Claim 14) such as those listed in Claim 15 (e.g, VEGF, IGFPB-1, angiopoietin-2, CXCL16, etc.), or reduces the up-regulation of the expression of angiogenic factors and/or inflammatory factors (Claim 16), and reduces the proliferation, or migration or tube formation in microvascular cells—such effects are a natural consequence (inherent) of administering the antibody in vivo.
Also, ‘407 teaches (Example 8) inhibition of HUVEC cells with the 2G4 antibodies which demonstrates a reduction in proliferation, or migration or tube formation in microvascular cells and teaches (Example 7) that SCF/c-KIT signaling (via phosphorylation of AKT) was inhibited by the 2G4 antibody.
Claim(s) 7-17 are also rejected under 35 U.S.C. 102(a)(1) as being either anticipated or otherwise available to the public by over Seo et al. (“A Fully Human Monoclonal Antibody Targeting c-KIT is a Potent Inhibitor of Choroidal Neovascularization in Murine Model of Neovascular Age-Related Macular Degeneration”, ARVO Annual Meeting Abstract, June 2021).
Absent evidence to the contrary, the abstract was published prior to applicant’s earliest effective filing date (07/16/2021) or the abstract was presented to the public at the 2021 Annual ARVO meeting which was held virtually May 1-7, 2021.
Seo et al. teach that in hypoxic human vascular endothelial cells, NN2101 completely blocked the SCF-induced activation of cKIT/β-catenin signaling pathways and increase in cell migration, tube formation, and proliferation. In mice with laser-induced CNV (choroidal neovascularization), an intravitreal injection of NN2101 (1.0 µg) significantly alleviated CNV formation with a comparable efficacy of aflibercept (2.5 µg). Seo et al. further teach that NN2101, a fully human monoclonal antibody targeting cKIT, may be a novel promising therapeutic for the treatment of ocular vascular diseases such as neovascular age-related macular degeneration (nAMD) and can enhance the potency of existing anti-vascular endothelial growth factor agents for the treatment of nAMD. The NN2101 antibody is the same as the 2G4 antibody above. Hence, the in vivo effects of administering the antibody would naturally inhibit the expression or activity of HIF-1α along with any other biological effects.
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.
Claim(s) 1-6 is/are rejected under 35 U.S.C. 103 as being unpatentable over KR20200040407A (‘407, published April, 2020, IDS) as applied to claims 7-17 above, and further in view of Yang et al., “Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: a comprehensive review”, Drug Design, Development and Therapy, 1857-1867, 2016.
‘407 teaches as set forth above, however, ‘407 does not teach the same eye patient population.
‘407 does not specifically teach preventing or treating an eye disease “that is refractory or non-responsive to existing eye disease drugs” including existing anti-VEGF drugs such as aflibercept, ranibizumab, bevacizumab, etc. (see claims 5-6).
Yang et al. teach (page 1857) that as of 2016 there were five anti-VEGF agents approved for the treatment of neovascular AMD (see Table 1, page 1858). And although these agents have shown dramatic breakthroughs in neovascular AMD treatment, some patients have a poor or no response to anti-VEGF agents with standardized treatment or experience a slow loss of efficacy of anti-VEGF agents after repeated administration over time. Yang et al. teach (pg 1858, 2nd column) that for these phenomena, researchers have offered various descriptions and explanations about the loss of the drug’s effec-tiveness, such as “incomplete response”, “poor response”, “nonresponse”, “unresponsive”, “tolerance”, “tachyphylaxis”, “treatment resistant”, “resistance to anti-VEGF”, “refractory to anti-VEGF”, and “resistance to anti-VEGF treatment”. The authors state that “Clarifying and consolidating these concepts are of great importance for an effective evaluation of switching to other anti-VEGF drugs, combination therapy, and multi-target treatment.” Further, Yang et al. teach (page 1858, 2nd col) that “Refractory AMD” is a really important concept, which contributes to finding the right time of switching treatments and making clinical decision more scientifically. Further, switching anti-VEGF medications is recommended when there is an acute decrease in the response to a drug. For example, Yang et al. teach (page 1862, 2nd column) that if tachyphylaxis occurs, clinicians should stop the treat-ment for a while or switch to a similar drug with different properties. The majority of these therapies involve switch-ing patients from bevacizumab to ranibizumab, from ranibizumab to bevacizumab, and from bevaci-zumab/ranibizumab to aflibercept.
Thus, one of ordinary skill in the art at the time of filing would consider it prima facie obvious to have included preventing or treating an eye disease “that is refractory or non-responsive to existing eye disease drugs” in the method of KR20200040407A. One would have been motivated to do so because the anti-VEGF antibodies previously known and approved (Yang et al., Table I) all inhibit VEGF-induced neovascularization which is similar to the anti-angiogenic effects of the 2G4 antibody as taught by the ‘407 application and all are designated and/or taught to be used for the treatment of eye diseases. Further, a person of ordinary skill in the art would know from Yang et al. that some patients have a poor or no response to these anti-VEGF agents or experience a slow loss of efficacy after repeated administration over time and that switching between anti-VEGF drugs can be a solution to refractory or non-responsive therapeutic administrations. For example, Yang et al. specifically taught that “Refractory AMD” is a really important concept, which contributes to finding the right time of switching treatments and making clinical decision more scientifically. Thus, in view of the combined teachings, it would be obvious to one of ordinary skill to have used the 2G4 antibody when other similar acting drugs (such as- pegaptanib, bevacizumab, ranibizumab, aflibercept, conbercept) became refractory or non-responsive to treatments of eye diseases.
Claim(s) 1-6 are rejected under 35 U.S.C. 103 as being unpatentable over Seo et al. (“A Fully Human Monoclonal Antibody Targeting c-KIT is a Potent Inhibitor of Choroidal Neovascularization in Murine Model of Neovascular Age-Related Macular Degeneration”, ARVO Annual Meeting Abstract, June 2021) as applied to claims 7-17 above in view of Yang et al., “Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: a comprehensive review”, Drug Design, Development and Therapy, 1857-1867, 2016.
Seo et al. teaches as set forth above, however, Seo et al. does not teach the same eye patient population. Seo et al. specifically references neovascular age-related macular degeneration which encompasses a maculopathy (Claim 3) and is equivalent to wet age-related macular degeneration (Claim 4).
Seo et al. does not specifically teach preventing or treating an eye disease “that is refractory or non-responsive to existing eye disease drugs” including existing anti-VEGF drugs such as aflibercept, ranibizumab, bevacizumab, etc. (see claims 5-6).
Yang et al. teach (page 1857) that as of 2016 there were five anti-VEGF agents approved for the treatment of neovascular AMD (see Table 1, page 1858). And although these agents have shown dramatic breakthroughs in neovascular AMD treatment, some patients have a poor or no response to anti-VEGF agents with standardized treatment or experience a slow loss of efficacy of anti-VEGF agents after repeated administration over time. Yang et al. teach (pg 1858, 2nd column) that for these phenomena, researchers have offered various descriptions and explanations about the loss of the drug’s effec-tiveness, such as “incomplete response”, “poor response”, “nonresponse”, “unresponsive”, “tolerance”, “tachyphylaxis”, “treatment resistant”, “resistance to anti-VEGF”, “refractory to anti-VEGF”, and “resistance to anti-VEGF treatment”. The authors state that “Clarifying and consolidating these concepts are of great importance for an effective evaluation of switching to other anti-VEGF drugs, combination therapy, and multi-target treatment.” Further, Yang et al. teach (page 1858, 2nd col) that “Refractory AMD” is a really important concept, which contributes to finding the right time of switching treatments and making clinical decision more scientifically. Further, switching anti-VEGF medications is recommended when there is an acute decrease in the response to a drug. For example, Yang et al. teach (page 1862, 2nd column) that if tachyphylaxis occurs, clinicians should stop the treat-ment for a while or switch to a similar drug with different properties. The majority of these therapies involve switch-ing patients from bevacizumab to ranibizumab, from ranibizumab to bevacizumab, and from bevaci-zumab/ranibizumab to aflibercept.
Thus, one of ordinary skill in the art at the time of filing would consider it prima facie obvious to have included preventing or treating an eye disease “that is refractory or non-responsive to existing eye disease drugs” in the method of Seo et al. One would have been motivated to do so because the anti-VEGF antibodies previously known and approved (Yang et al., Table I) all inhibit VEGF-induced neovascularization which is similar to the anti-angiogenic effects of the NN2101 antibody and all are designated and/or taught to be used for the treatment of eye diseases. Further, a person of ordinary skill in the art would know from Yang et al. that some patients have a poor or no response to these anti-VEGF agents or experience a slow loss of efficacy after repeated administration over time and that switching between anti-VEGF drugs can be a solution to refractory or non-responsive therapeutic administrations. For example, Yang et al. specifically taught that “Refractory AMD” is a really important concept, which contributes to finding the right time of switching treatments and making clinical decision more scientifically. Thus, in view of the combined teachings, it would be obvious to one of ordinary skill to have used the NN2101 antibody when other similar acting drugs (such as- pegaptanib, bevacizumab, ranibizumab, aflibercept, conbercept) became refractory or non-responsive to treatments of eye diseases.
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 1-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 12540180 (‘180) in view of Yang et al., “Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: a comprehensive review”, Drug Design, Development and Therapy, 1857-1867, 2016.
‘180 issued claims to the antibody itself which is the same antibody used in the currently claimed methods. Patented claims 1, and 3-4 are drawn to the same CDRs and VH and VL regions as used in the current methods. The nucleic acids encoding the antibody and vectors comprising the nucleic acids are also claimed in ‘180 (5-7). The patent teaches that the antibody can be used to treat diseases of the eye such as diabetic retinopathy, retinopathy of prematurity, corneal graft rejection, macular degeneration, neovascular glaucoma, and proliferative retinopathy. (The portion of the specification of the reference that describes subject matter that falls within the scope of a reference claim may be relied upon to properly construe the scope of that claim. In particular, when ascertaining the scope of the reference’s claim(s) to a compound, the examiner should consider the reference’s specification, including all of the compound’s uses that are disclosed. See Sun Pharm. Indus., 611 F.3d at 1386-88, 95 USPQ2d at 1801-02.). Further, issued claim 10 broadly encompasses treating any angiogenic disease with the antibody or nucleic acid encoding the antibody which overlaps with current claims 7-17 or a retinal or macular disease as currently claimed in Claim 2 and would further encompass various ocular diseases such as choroidal angiogenesis (current claim 3) or wet age-related macular degeneration (current claim 4). As to including preventing or treating an eye disease “that is refractory or non-responsive to existing eye disease drugs”, it would be obvious to use the patented antibody as switching between known anti-angiogenic drugs for ocular purposes is well known in view of the teachings of Yang et al. as set forth in the 103/obviousness rejection as set forth above. Thus, there is also overlapping claimed subject matter between the current application and US 12540180.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GARY B NICKOL, Ph.D. whose telephone number is (571)272-0835. The examiner can normally be reached M-F 9AM-5:30PM.
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/GARY B NICKOL/Primary Examiner, Art Unit 1643
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