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 .
Response to Amendment
Applicant’s response, filed 06 October 2025, has been received and entered. Claims 1, 9, 11 and 13 have been amended and claims 2-4, 6-8, 10, 14 and 20-28 have been canceled. Claims 1, 5, 9, 11-13 and 15-19 are currently pending.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Any objection or rejection of record which is not expressly repeated in this action has been overcome by Applicant's response and withdrawn.
Applicant's arguments filed 06 October 2025 have been fully considered but are not found to be persuasive.
Drawings
The drawings were received on 06 October 2025. These drawings are acceptable.
Claim Objections
Claim 1 is objected to because of the following informalities:
Claim 1 recites “the ocular disorder is ischemia-related retinopathies”. This recitation is grammatically incorrect as “ocular disorder” is singular and “retinopathies” is plural. This recitation appears to imply that the ocular disorder would necessarily need to be multiple ischemia-related retinopathies in order to be included in the scope of the claim.
Claim 1 is directed to treating a subject “in need of treatment for pathological angiogenesis”, but the claim does not actually recite those conditions which would be considered “pathological angiogenesis”. The claim limits the subject based on ocular disorder/cell proliferative disorder. While some of the disorders which are recited may be considered conditions of pathological angiogenesis, the claim does not make clear that the condition which is being treated is the condition which the subject possesses. For example, the subject could have “traumatic eye injury” which may have no relation to pathological angiogenesis, but the claim encompasses that subject. That subject could have a cancer which is being treated but also have a traumatic eye injury (loss of an eye, for example) which is not being treated. It is suggested that the claim be reworded such that it is clear what condition is being treated.
For example, claim 1 could recite “a method of inhibiting pathological angiogenesis in a subject in need thereof….wherein the pathological angiogenesis is ….” and where the claim recites the various disorders to be treated.
Claim 1 is also objected to because it recites a lot of verbiage which is not necessary for the understanding of the claim. The claim currently recites “glycosaminoglycan linked … to an anti-vascular endothelial growth factor antibody (anti-VEGF antibody), wherein (a) the anti-VEGF antibody is bevacizumab, (b) the glycosaminoglycan binds vascular endothelial growth factor (VEGF) and the anti-VEGF antibody, and (c) the glycosaminoglycan is heparin”. This recitation amounts to “heparin linked either covalently or non-covalently to bevacizumab”. The use of “(a), (b), (c) is confusing as it implies elements yet there are only two components to the compound being administered.
Claim 1 also could be further clarified as the claim limits “cell proliferative disorder” to cancer in the last paragraph. Limiting the verbiage to cancer would result in clarity of what is being claimed.
Claim 5 also could be edited to more clearly reflect the claimed invention as claim 1 is limited to heparin for the glycosaminoglycan yet claim 5 still refers to the genus.
Appropriate correction is required.
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.
Claim 13 is 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 13 recites “wherein the subject has the cell proliferative disorder” and depends from claim 1. However, there is a lack of antecedent basis for “the cell proliferative disorder” in claim 1. Claim 1 states that “the cell proliferative disorder is a cancer that is breast cancer, kidney cancer, cervical cancer”, etc. Therefore, there is no singular “cell proliferative disorder” and the metes and bounds of the claim cannot be determined.
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, 5, 8-9, 11 and 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO 20174/100470A1 (Healy et al.).
Healy et al. teach a method of treating ocular disease or disorder by direct administration into the eye a conjugate comprising a biologically active polypeptide and a biocompatible polymer (see abstract). Healy et al. teach that the biologically active polypeptide is a VEGF antagonist (see page 2) which can be a soluble receptor, a protein or an antibody specific for VEGF (see [0087], [0095]-[0097]) and specifically teach bevacizumab as an antibody for VEGF (see [0093]). Healy et al. also teach that the polymer can be hyaluronic acid, heparin, chondroitin, chondroitin sulfate, heparin sulfate and copolymers thereof (see page 1). Healy et al. specifically teaches that suitable natural polymers include glycosaminoglycans (see [0079]) and particularly teaches hyaluronic acid and hyaluronic acid derivatives, including sulfated or N-sulfated hyaluronic acid (see [0083]). Healy et al. teach that the polymer and VEGF antagonist are linked covalently (such as by a peptide linker (see [0099])) or via conjugation (see [00100]). Healy et al. teach that the ratio of the polymer to polypeptide ratio can be varied and the ratio range is consistent with that of the instant claims (see [00116]). Healy et al. teach that ocular disorders are treated with the disclosed method including macular degeneration, choroidal neovascularization, macular edema, etc. (see [00126]-[00128]) as well as subjects with pathological angiogenesis in the eye due to an ocular disease or disorder (see [00130]) and that administration can be by any of a number of routes including intravitreal (see [00125)).
While Healy et al. do not reduce to practice an anti-VEGF antibody linked covalently or non-covalently to heparin wherein the antibody is bevacizumab, Healy et al. clearly teach the construct of a VEGF inhibitor linked to a polymer and also teach the specific elements of the construct to be used in the claimed method of treating ocular diseases which are conditions of pathological angiogenesis. One would have had a reasonable expectation of success because Healy et al. reduced to practice a conjugate of soluble VEGF receptor and hyaluronic acid (see [00135]) and demonstrated its effectiveness in inhibiting corneal angiogenesis (see [00137]). Therefore, the claims are obvious over the disclosure of Healy et al. for the reasons set forth above.
Response to Arguments
Applicant argues at page 8 of the response that claim 1 has been amended to recite specific diseases to be treated and that Healy fails to teach, suggest, or motivate one of ordinary skill in the art to teat the recited diseases with the claimed anti-VEGF antibody linked to heparin.
Applicant’s arguments have been fully considered, but are not found persuasive. First, the claim does not actually recite the specific diseases to be treated. Claim 1 is directed to a method of treating a subject in need of treatment for pathological angiogenesis and then recites that the subject has a particular condition. While it may be implied that the “pathological angiogenesis” is related to the condition of the subject, the claim does not expressly state that it is the recited conditions that the subject possesses is that which is being treated for “pathological angiogenesis”.
Next, Healy et al. teach that ocular disorders are treated with the disclosed method including macular degeneration, choroidal neovascularization, macular edema, etc. (see [00126]-[00128]) as well as subjects with pathological angiogenesis in the eye due to an ocular disease or disorder (see [00130]). While Healy et al. may not specifically enumerate the various ocular disorders which cause pathological angiogenesis in the eye, those of ordinary skill in the art before the effective filing date of the claimed invention would have been aware of ocular conditions which include pathological angiogenesis as one of the symptoms and would have been apprised of which ocular diseases/disorders would be responsive to inhibition of VEGF by bevacizumab, absent evidence to the contrary.
Claim(s) 1, 8-9, 11-13 and 15-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Pat. Pub. 2017/0096479A1 (Koenig et al.).
Koenig et al. teach a method of treating disorders of pathological angiogenesis with an anti-VEGF antibody conjugate wherein the disorders are ocular disorders and cell proliferative disorders (see [0004]). Koenig et al. teach conjugation of anti-VEGF antibodies with hyaluronic acid (see [0045]) and with glycosaminoglycans, heparin, heparin sulfate and chondroitin sulfate (see [0484]). Koenig et al. teach that the anti- VEGF antibodies can be covalently conjugated or non-covalently conjugated to the polymer (such as by a biotin-streptavidin linkage) (see [0511]). Koenig et al. teach that the pathological angiogenesis is an ocular disorder or a cell proliferative disorder (see [0036]-[0038]). Koenig et al. teach that the method can further comprise administering a second agent which can be a chemotherapeutic agent (see [0042] and [0192]). Koenig et al. also teaches that administration of the antibody conjugate can be by any number of routes including intravitreally, topically and parenterally (see [0058]). Koenig et al. also teaches a number of different VEGF antagonists (see [0185]) and specifically teach bevacizumab as the anti-VEGF antibody.
While Koenig et al. do not reduce to practice an anti-VEGF antibody linked covalently or non-covalently to heparin wherein the antibody is bevacizumab, Koenig et al. clearly teach the construct of a VEGF antibody conjugated to a polymer and also teach the specific elements of the construct to be used in the claimed method of treating ocular diseases which are conditions of pathological angiogenesis. One would have had a reasonable expectation of success because Koenig et al. reduced to practice a conjugate of an anti-VEGF antibody and hyaluronic acid (see [0620]). Therefore, the claims are obvious over the disclosure of Koenig et al. for the reasons set forth above.
Response to Arguments
Applicant argues at page 12 of the response that Koenig teaches compositions comprising anti-VEGF antibodies which Koenig generated and that the composition can further include a second agent which can be an anti-angiogenic agent which can be an anti-VEGF antibody. Applicant argues that Koenig’s reference to bevacizumab is only in regards to bevacizumab being a VEGF antagonist and the second agent of the composition of paragraph [0044]. Applicant concludes that Koenig does not reasonably teach, suggest, or motivate one of ordinary skill in the art to produce the claimed bevacizumab linked to heparin, or its use in the claimed method.
Applicant’s arguments have been fully considered, but are not found persuasive. Konenig et al. clearly teach a method of treating disorders of pathological angiogenesis with an anti-VEGF antibody conjugate wherein the disorders are ocular disorders and cell proliferative disorders (see [0004]). While the invention of Koenig et al. focuses on the anti-VEGF antibodies which were created/disclosed, the teaching of Koenig et al. regarding conjugation of anti-VEGF antibodies with hyaluronic acid (see [0045]) and with glycosaminoglycans, heparin, heparin sulfate and chondroitin sulfate (see [0484]) is a teaching that is applicable to any anti-VEGF antibody, regardless of whether or not that antibody is one that Koenig et al. generated or if it is an anti-VEGF antibody of the art. While Koenig et al. reference bevacizumab in the context of a second agent, it is clearly an anti-VEGF antibody and would be appropriate for conjugation as set forth in [0045]. With regard to picking and choosing of elements from the specification, one of ordinary skill in the art before the effective filing date of the claimed invention would have selected bevacizumab as the anti-VEGF antibody because it is a commonly used anti-VEGF antibody and possibly one of the most well-known anti-VEGF antibodies in the art. The use of bevacizumab for treating ocular disorders with pathological angiogenesis as well as cancers with pathological angiogenesis is well documented in the art. Therefore, conjugating bevacizumab to heparin would have been prima facie obvious over the teachings of Koenig et al. for the reasons of record.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/Christine J Saoud/Primary Examiner, Art Unit 1645