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 .
Claim Status
Claims 1-2, 9, 14-15, 17, 39, 48-58, and 60 are pending. Claims 1-2, 9, 15, 17, 39, 48-49, and 52-53 were amended, and claim 60 was added in the response filed 10/13/2025. Claims 15, 49, 51, and 56-57 are withdrawn as directed to a non-elected species. Claims 1-2, 9, 14, 17, 39, 48, 50, 52-55, 58, and 60 are presently considered.
Election/Restrictions
Applicant’s election of Group I (methods) and the species corresponding to Example 7 in the reply filed on 10/13/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Example 7 pertains to a combination therapy of AIBP, APOA-I, and Anti-VEGF Antibody, for the treatment of Choroidal neovascularization1 (CNV) (see Spec. filed 11/18/2022 at ¶[0125]). The originally elected species is understood to be the treatment of a laser-induced CNV mouse model with AIBP, apoA-1, and an anti-VEGF antibody (see Spec. filed 11/18/2022 at ¶¶[0134]-[0135], Figures 15E and 21; see Reply filed 10/13/2025 at 9), via intravitreal injection2. The mouse model is an admitted obvious variant for humans, and therefore the elected species is understood to include both CNV mouse models and human individuals (see Reply filed 10/13/2025 at 8-9). The compounds utilized within the originally elected species of method are understood as follows: ApoA-1 is SEQ ID NO: 33; AIBP is understood to be SEQ ID NO: 14; and the Anti-VEGF agent is understood to be the Anti-VEGF antibody of “AF-493-NA”5.
The Applicant did not identify what claims filed 10/13/2025 read upon the originally elected species (see, e.g., Requirement mailed 7/02/2025 at 6 at 2nd full ¶, noting that the “reply must also identify the claims readable on the elected species, including any claims subsequently added”). To facilitate compact prosecution, Examiner notes that the originally elected species is reasonably inferred to read upon instant claims 1-2, 9, 14, 17, 39, 48, 50, 52-54, 58, and 60.
However, claims 15, 49, 51, and 55-57 do not reasonably read upon the originally elected species. Claim 15 requires one or more additional therapies in addition to those identified at claim 1. Claim 49 requires “the AIBP composition” to further comprise one or more anti-VEGF agents, but the elected species identifies that AIBP is SEQ ID NO: 1 and that only one anti-VEGF antibody is present; therefore the species does not “further comprise” additional anti-VEGF agents. Claim 51 requires specific conditions not identified as present in the originally elected species of laser-induced CNV mouse model (see Spec. filed 11/18/2022 at ¶¶[0134]-[0135], Figures 15E and 21; see Reply filed 10/13/2025 at 9). Claim 55 does not recite AF-493-NA, and Applicant has not identified that AF-493-NA is the same as any enumerated antibody at claim 55. Furthermore, claims 56-57 require small molecule or non-antibody agents rather than an anti-VEGF antibody, and therefore do not read upon the originally elected species.
Following extensive search and examination, the originally elected species has been deemed anticipated and/or obvious in view of the prior art as applied below. Per MPEP § 803.02(III)(A),
Following election, the Markush claim will be examined fully with respect to the elected species and further to the extent necessary to determine patentability. Note that where a claim reads on multiple species, only one species needs to be taught or suggested by the prior art in order for the claim to be anticipated or rendered obvious...
If the Markush claim is not allowable, the provisional election will be given effect and examination will be limited to the Markush claim and claims to the elected species, with claims drawn to species patentably distinct from the elected species held withdrawn from further consideration.
Accordingly, claims 1-2, 9, 14, 17, 39, 48, 50, 52-55, 58, and 60 are rejected in view of the originally elected species and claims that do not read upon the originally elected species are withdrawn.
During the search and examination of the originally elected species, art pertinent to one or more non-elected species at claim 55 was incidentally discovered. Although examination has not been extended beyond the non-elected species identified above per MPEP § 803.02, as a courtesy to the Applicant, claim 55 been examined in view of the art applied below.
Claims 15, 49, 51, and 55-57 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/13/2025.
Claims 1-2, 9, 14, 17, 39, 48, 50, 52-55, 58, and 60 are presently considered.
Priority
The priority claim to US Provisional Application 63/030421 (filed 5/27/2020) is acknowledged.
Information Disclosure Statement
The IDS filed 11/18/2022; 03/17/2023; and 07/16/2024 are each acknowledged and presently considered.
ARVO20196 refers to the Association for Research in Vision and Ophthalmology (ARVO) conference in Canada from April 28 to May 2019, wherein research abstracts were presented (see, e.g., ARVO2019, passim). Fu7 is cited herein to evidence that the abstract “AIBP suppresses choroidal neovascularization (CNV) by enhancing cholesterol efflux” was presented at ARVO2019 between April 28 to May 2019 (see, e.g., Fu at abstract at page 4, noting the disclosure stating “This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 29 - May 2, 2019”). Fu shares named authors in common with the instant Application, and therefore this meeting was known to the inventors at the time of filing. Applicant is advised that any posters, presentations, etc. presented at any conference regarding CNV, AMD, ApoA-I, AIBP, and/or anti-VEGF agent is relevant and material to a determination of patentability, and should be placed on record in an IDS (see, e.g., MPEP § 2001, 37 C.F.R. 1.56).
Applicant should note that one or more documents disclosed on the IDS form submitted on 07/16/2024 were not considered since they did not conform to 37 CFR 1.98(b) by providing a proper date, as 37 CFR 1.98(b) requires that each publication must be identified by publisher, author (if any), title, relevant pages of the publication, and date and place of publication. The date of publication supplied must include at least the month and year of publication, except that the year of publication (without the month) will be accepted if the applicant points out in the information disclosure statement that the year of publication is sufficiently earlier than the effective U.S. filing date and any foreign priority date so that the particular month of publication is not in issue. See MPEP 609.04(a). Here, the earliest priority claim is to US Provisional Application 63/030421, filed 5/27/2020; therefore, all documents published in 2019 or later must be accompanied by both month and date of publication.
References that were not considered have been indicated by strike-though on the attached IDS forms. Although not considered, these documents have been placed in the application file, but the information referred to therein has not been considered as to the merits. Applicant is advised that the date of any re-submission of any item of information contained in this information disclosure statement or the submission of any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the statement, including all certification requirements for statements under 37 CFR 1.97(e). See MPEP § 609.05(a).
Specification
The disclosure is objected to because of the following informalities:
Sequence Listing: The instant disclosure is objected to for not complying with 37 C.F.R. 1.821 as detailed in MPEP §§ 2421–2424. Specifically, the instant application does not comply with 37 C.F.R. 1.821(b)-(e). The instant claims and/or disclosure contain references or disclosures of amino acid sequences that should be accompanied by a sequence listing and identified using "SEQ ID NOs” as prescribed (see, MPEP §§ 2421–2424). Specifically, the pending claims and the original disclosure refer to sequences by SEQ ID NO (e.g., instant claims 1 and 39, Spec. filed 11/18/2022 at ¶¶[0064], [0081], passim), but no corresponding sequence listing has been placed on record.
Drawings
The drawings are objected to under 37 CFR 1.83(a) because they fail to show colors as described in the specification (see, e.g., Spec. filed 11/18/2022 at ¶¶[0032]-[0033], [0130]-[0131], referring to “orange” in Figures 13-14; see id. at ¶¶[0032], [0037] referring to “red” in Figures 14 and 18; see id. at ¶¶[0130]-[0131] referring to “yellow” in Figures 13-14; see id. at ¶¶[0029], [0037] referring to “blue” in Figures 10 and 18; see id. at ¶¶[0029] referring to “green” in Figure 10; these examples are not intended to be exhaustive). Any structural detail that is essential for a proper understanding of the disclosed invention should be shown in the drawing. MPEP § 608.02(d). 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.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Claim Interpretation
For purposes of examination, the claim scope has been interpreted as set forth below per the guidance set forth at MPEP § 2111. If Applicant disputes any interpretation, Applicant is invited to unambiguously identify any alleged misinterpretations or specialized definitions in the subsequent response to the instant action. Applicant is advised that a specialized definition should be properly supported and specifically identified (see, e.g., MPEP § 2111.01(IV), describing how Applicant may act as their own lexicographer).
Claims 1 and 39 are representative of the pending claim scope. The applicable claim interpretation is discussed below.
Regarding the preamble of claims 1 and 39, per MPEP § 2111.02, “where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation”. Here, the body of claims 1 and 39 are each understood to recite a structurally complete invention, and therefore the preamble is deemed fully satisfied by prior art that satisfies the steps and structures recited in the body of the claim (see also MPEP § 2111.04(I), noting that “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure”).
“Comprising” is an open-ended transitional term (see, e.g., MPEP § 2111.03(I)), wherein additional steps or components are not excluded. However, “‘[c]omprising’ is a term of art used in claim language which means that the named elements are essential” (see, e.g., id.; see also Genentech, Inc. v. Chiron Corp., 112 F.3d 495, 501, 42 USPQ2d 1608, 1613 (Fed. Cir. 1997)).
“Treating” is not specifically defined, but is reasonably understood to include all types of treatment, including prophylactic treatment (see, e.g., Spec. filed 11/18/2022 at ¶¶[0008]-[0009], [0011]).
ApoA-I is a protein consisting of SEQ ID NO: 3 (see Spec. filed 11/18/2022 at ¶[0064]), wherein SEQ ID NO: 3 is disclosed as
MKAAVLTLAVLFLTGSQARHFWQQDEPPQSPWDRVKDLATVYVDVLKDSGRDYVSQFEGSALGKQLNLKLLDNWDSVTSTFSKLREQLGPVTQEFWDNLEKETEGLRQEMSKDLEEVKAKVQPYLDDFQKKWQEEMELYRQKVEPLRAELQEGARQKLHELQEKLSPLGEEMRDRARAHVDALRTHLAPYSDELRQRLAARLEALKENGGARLAEYHAKATEHLSTLSEKAKPALEDLRQGLLPVLESFKVSFLSALEEYTKKLNTQ
(see Spec. filed 11/18/2022 at ¶[0064])
“ApoA-I binding protein” (“AIBP”) is understood to be a secreted protein, and is also known in the art as also known as apolipoprotein A-I binding protein, AI-BP, apoA-I binding protein, NAD(P)H-hydrate epimerase, NAXE, NAD(P)HX epimerase, PEBEL, YJEFNl, and APOA1BP (see Spec. filed 11/18/2022 at ¶¶[0050]-[0055]). AIBP is understood to be SEQ ID NO: 1 (see Spec. filed 11/18/2022 at ¶[0081]). However, SEQ ID NO: 1 is referred to as AJ315849.18 (see id.), but the sequence provided at [0081] actually corresponds to NP_658985.29:
MSRLRALLGLGLLVAGSRVPRIKSQTIACRSGPTWWGPQRLNSGGRWDSEVMASTVVKYLSQEEAQAVDQELFNEYQFSVDQLMELAGLSCATAIA KAYPPTSMSRSPPTVLVICGPGNNGGDGLVCARHLKLFGYEPTIYYPKRPNKPLFTALVTQCQKMDIPFLGEMPAEPMTIDELYELVVDAIFGFSFKGDVREPFHSILSVLKGLTVPIASIDIPSGWDVEKGNAGGIQPDLLISLTAPKKSATQFTGRYHYLGGRFVPPALEKKYQLNLPPYPDTECVYRLQ
(see Spec. filed 11/18/2022 at ¶[0081]). The sequences of AJ315849.1 and NP_658985.2 differ because the amino acid bolded above is leucine rather than valine in AJ315849.1. Both sequences are known in the prior art, share 287/288 amino acid resides (>99.6% identity), and both are understood to be an art-recognized human AIBP within the scope of the instant claims (see, e.g., AJ315849 at § “Keywords”; see, e.g., NP_658985.2 at 4 at § “Protein”, referring to it as “apoA-I binding protein”, 3-4 at § Comment). For purposes of applying prior art, the sequence set forth and identified explicitly as “SEQ ID NO: 1” is understood to be the sequence of the AIBP protein (i.e., NP_658985.2).
The “Anti-VEGF agent” of AF-493-NA used in the originally elected species (see, e.g., Spec. filed 11/18/2022 at ¶[0133]) is not provided with a sequence, but is understood to be a mouse antibody (see search notes).
At claim 1 and 39, the reference to a “functionally active fragment or derivative” is not explicitly defined in the specification, but is reasonably interpreted in view of the description of “functional” and “functionally equivalent derivative” (see Spec. filed 11/18/2022 at ¶[0079]), which notes that
Whether or not a given polypeptide or polynucleotide is "functional" may be determined by first selecting an appropriate function to assess. For example, functionality of AIBP variants may be assessed in vitro or in vivo for the ability of the variants to attenuate neovascularization, for example, by improving removal of cholesterol from endothelial cells and/or macrophages, reducing inflammation, and/or restoring macrophages' ability to inhibit angiogenesis. Functionality of AIBP variants may also be assessed in vitro or in vivo for the ability of the variants to increase the efficacy of an anti-VEGF agent in inhibiting angiogenesis. In some cases, a functional molecule may be one that exhibits the desired function to a statistically significant degree (e.g. p<0.05; <0.01; <0.001).
Accordingly, a “functionally active fragment or derivative” is a functional limitation attempting to limit the scope of the claims unspecified structures having unspecified functions that Applicant desires and hopes for the structures to achieve, but fails to provide clear guidance of what structures do or do not satisfy the functional limitation. This has necessitated rejections under 35 USC 112. For purposes of applying prior art, the limitation is presumed to be fully satisfied by all fragments comprising “at least 90” percent identity with SEQ ID NO:1 and any derivative having “1…or more variations” compared to SEQ ID NO: 1.
“Anti-VEGF agent” is understood to include antibodies against VEGF including brolucizumab, pegaptanib (MacugenTM), bevacizumab (Avastin™), conbercept (Lumitin™), ranibizumab (Avastin® and LucentisTM) (see Spec. filed 11/18/2022 at ¶[0061]). The term also includes small molecules such as lapatinib, sunitinib, sorafenib, axitinib, pazopanib, AZ2171 ( cediranib), AAV2-sFLT-1, AAV2-sFLT01, and aflibercept (see Spec. filed 11/18/2022 at ¶[0062]).
“Therapeutically effective amount” is understood in view of the description and is understood to include the range of “about 1 mg/kg” to “about 100 mg/kg” of body weight for AIBP, (see Spec. filed 11/18/2022 at ¶[0095]), 0.6-4.8µg of AIBP with a ratio of AIBP to ApoA-I of 1:4.2 (see Spec. filed 11/18/2022 at ¶[0133]) and 5 ng to 5 mg of anti-VEGF antibody (see Spec. filed 11/18/2022 at ¶¶[0135], [0141]). In the absence of explicitly required amounts, any prior art disclosure disclosing successful or therapeutic results are understood to necessarily and inherently involve a therapeutically effective amount as required by the claims.
An “individual” is understood to include at least humans and mice (see Spec. filed 11/18/2022 at ¶¶[0134]-[0135]).
Claims 9 recites a “wherein” clause that recites an intended or expected result. Per MPEP § 2111.04(I), “Claim scope is not limited by claim language that . . . . does not require steps to be performed, or by claim language that does not limit a claim to a particular structure”, and further states that a “whereby clause” in a claim “is not given weight when it simply expresses the intended result of a process step positively recited”. Here, the “wherein” clause does not unambiguously correspond to a clear structure/function relationship in the original disclosure, and therefore is not a functional limitation. Rather, the “wherein” clause is understood to merely recite an intended or expected result fully satisfied by the positively recited steps and/or structures set forth in the body of the claim. Therefore, the “wherein” clause at claim 9 is understood to be fully satisfied by all prior art embodiments that satisfy the positively recited, active method steps set forth in the body of claim 1.
Claims 14 recites a “wherein” clause that recites an intended or expected result. Per MPEP § 2111.04(I), “Claim scope is not limited by claim language that . . . . does not require steps to be performed, or by claim language that does not limit a claim to a particular structure”, and further states that a “whereby clause” in a claim “is not given weight when it simply expresses the intended result of a process step positively recited”. Here, the “wherein” clause does not unambiguously correspond to a clear structure/function relationship in the original disclosure, and therefore is not a functional limitation. Rather, the “wherein” clause is understood to merely recite an intended or expected result fully satisfied by the positively recited steps and/or structures set forth in the body of the claim. Therefore, the “wherein” clause at claim 14 is understood to be fully satisfied by all prior art embodiments that satisfy the positively recited, active method steps set forth in the body of claim 1.
Claim 50 recites the active method step of “wherein the individual is determined to be at risk of having resistance to one or more anti-VEGF agents”. The specification does not elaborate on how this step is performed, but identifies that patients treated with anti-VEGF agents may “experience a slow loss of efficacy of anti-VEGF agents after repeated administration over time”, and that “a significant number of patients have a poor response or are nonresponsive to standardized treatment with anti-VEGF agents” (see Spec. filed 11/18/2022 at ¶[0003]). In addition, patients having the risk factors identified at [0112] are understood to be “at risk” see Spec. filed 11/18/2022 at ¶[0112], noting that smoking, obesity, pregnancy, race, etc. are “risk factors”). Accordingly, all individuals having or at risk of having CNV are reasonably inferred to be “at risk of having” resistance to one or more anti-VEGF agents; and therefore patients having CNV, AMD, histoplasmosis, angioid streaks, pathological myopia, choroidal ruptures, or are otherwise being treated with anti-VEGF agents are understood to satisfy the limitation of claim 50.
Additional claim interpretations are provided below.
Claim Objections
Claims 1 and 39 are objected to because of the following informalities:
Claims 1 and 39 repeat the phrase “at least 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to SEQ ID NO: 1”; therefore, the claim encompasses all fragments or derivatives that share at least 90% identity with SEQ ID NO: 1. Accordingly, references to “91, 92, 93, 94, 95, 96, 97, 98, or 99%” are not further limiting to the pending claim scope. Redundant and superfluous language should be removed to enhance claim clarity and to minimize potential confusion.
Claims 1 and 39 repeat the phrase “the derivative comprises 1, 2, 3, 4, 5, or more variations compared to SEQ ID NO: 1”; therefore, the claim encompasses all derivatives having “1 or more” variations compared to SEQ ID NO: 1. Accordingly, references to “2, 3, 4, 5” are not further limiting to the pending claim scope. Redundant and superfluous language should be removed to enhance claim clarity and to minimize potential confusion.
Appropriate correction is required.
Claim Rejections
Claim Rejections - 35 USC § 112(b)
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 1-2, 9, 14, 17, 39, 48, 50, 52-55, 58, and 60 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.
Claims 1 and 39 recites the limitation "the N-terminus". There is insufficient antecedent basis for this limitation in the claim. For purposes of applying prior art, a fragment comprising “the N-terminus” is understood any peptide comprising the N-terminal amino acid of SEQ ID NO: 1 (i.e., “M” or Met).
Claims 1 and 39 recites the limitation "the C-terminus". There is insufficient antecedent basis for this limitation in the claim. For purposes of applying prior art, a fragment comprising “the N-terminus” is understood any peptide comprising the C-terminal amino acid of SEQ ID NO: 1 (i.e., “Q”, Gln).
Claims 1 and 39 recite the term “variation” in the phrase “the derivative comprises 1, 2, 3, 4, 5, or more variations compared to SEQ ID NO: 1”. “Variation” is a relative term which renders the claim indefinite. The term “variation” 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. More specifically, it is unclear if a “variation” includes only single-amino acid changes (i.e., one substitution, deletion, or addition of a single amino acid is “1” variation), or if a “variation” includes multiple amino acids altered relative to SEQ ID NO: 1 (i.e., a truncation, deletion, or substitution of 20 contiguous amino acids is “1” variation; i.e., a retroinverso variant, or full-replacement of the backbone is “1” variation, etc.). Accordingly, claims 1 and 39 are rejected as indefinite. For purposes of applying prior art, the claim is broadly understood to include any “derivative comprising 1… or more variations compared to SEQ ID NO: 1”, wherein “or more” is unlimited, and therefore a “derivative” as claimed is required to have 0% sequence identity is required with instant SEQ ID NO: 1.
Claim 2 recites the phrase “associated with age-related macular degeneration” in the phrase “wherein the choroidal neovascularization is associated with age-related macular degeneration”. “Associated with” is a relative term which renders the claim indefinite. The term “Associated with” 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. More specifically, it is unclear if a “associated with” requires (i) that the choroidal neovascularization be “caused by” age-related macular degeneration, (ii) that the choroidal neovascularization be “a risk factor” for developing age-related macular degeneration, (iii) that choroidal neovascularization and age-related macular degeneration are present as comorbidities in a single patient population, or (iv) if the phrase is intended to exclude non-AMD patients having ocular histoplasmosis, angioid streaks, pathological myopia, choroidal ruptures, or other causes of CNV other than AMD and “wet AMD” (see Spec. filed 11/18/2022 at ¶[0003]). For purposes of applying prior art, the claim is broadly understood to include the originally elected species, wherein “laser induced CNV” mouse model is not “caused by” AMD, but the model is explicitly disclosed as “an AMD animal model for anti-VEGF resistance”, presumably because it models the angiogenesis and inflammation of CNV “which may contribute to anti-VEGF resistance” (see Spec. filed 11/18/2022 at ¶[0134]). If the limitation is intended to limit the claim scope to a patient population, Examiner suggests amending claim 2 to simply recite “wherein the individual has age-related macular degeneration”.
Claim 14 recites “the AIBP composition” at line 2. There is insufficient antecedent basis for this limitation in the claim. Although claim 1 recites “AIBP” and “a composition comprising apoA-I binding protein (AIBP)” (see, e.g., instant claim 1), claim 1 does not recite an “AIBP composition” (see, e.g., Nystrom v. TREX Co., Inc., 424 F. 3d 1136, 1143 (Fed. Cir. 2005), explaining that "When different words or phrases are used in separate claims, a difference in meaning is presumed). Accordingly, claim 14 is rejected as indefinite. For purposes of applying prior art and for consideration under 35 USC 112(d), claim 14 is interpreted as meaning “wherein the provision of the composition reduces resistance to anti-VEGF agents”.
Claim 17 refers to a singular agent, namely “the anti-VEGF agent”, which is identified as a singular chemical compound at claim 1 (“an anti-VEGF agent”) and in the specification (see Spec. filed 11/18/2022 at ¶¶[0061]-[0062]), but then appears to attempt to redefine the term “the anti-VEGF agent” to collectively “comprise” “one or more” different and distinct structures (see, e.g., claim 17(a)-17(c)). Accordingly, the usage of “an anti-VEGF agent” to refer to potentially numerous different and distinct anti-VEGF agents, or otherwise to refer to an unknown structural amalgamation of numerous compounds, renders the claim scope indefinite because the meaning of “an anti-VEGF agent” at claim 17 appears inconsistent with the usage of the term at claim 1. Clarification is required. For purposes of applying prior art, claim 17 is understood to refer to “The method of claim 1, wherein the composition …..
Claim 55 refers to “the VEGF agent”. There is insufficient antecedent basis for this limitation in the claim. Claim 55 depends from claim 50, which depends from claim 39. Claim 39 is understood to require a patient population previously treated with or currently undergoing “anti-VEGF therapy” (see claim 39 at lines 1-2), wherein “anti-VEGF therapy” is understood to necessarily and inherently require therapy by administering an anti-VEGF agent. However, Claim 50 defines the patient population as “wherein the individual is determined to be at risk of having resistance to one or more anti-VEGF agents”. Accordingly, the “anti-VEGF agent” utilized in “anti-VEGF therapy” as recited at claim 39 may differ from the “resistance” defined at claim 50. Therefore, it is unclear if claim 55 refers to the “anti-VEGF agent” utilized in “anti-VEGF therapy” as recited at claim 39, or refers to the resistance at claim 50. Accordingly, claim 55 is rejected as indefinite. For purposes of applying prior art, claim 55 is understood to refer to the actively administered anti-VEGF agent required to constitute an “anti-VEGF therapy” as recited at the preamble of claim 39. Accordingly, claim 55 is interpreted as reciting “wherein the anti-VEGF therapy comprises the administration of one or more antibodies selected from…”.
Claim 55 confusing refers to the singular molecule of “the anti-VEGF agent” as an open-ended composition capable of comprising “one or more antibodies” (see, e.g., instant claim 55). As explained above, “anti-VEGF agent” is understood in view of the disclosure and independent claims to refer to a single molecule (see Spec. filed 11/18/2022 at ¶¶[0061]-[0062]). Accordingly, it is unclear if claim 55 contains a typographical error, or is an attempt to redefine “the anti-VEGF agent” as either a (i) potentially multi-component composition or (ii) an unknown amalgamation comprising potentially multiple structures in a single biomolecule conjugated in unspecified manner. Accordingly, claim 55 is rejected as indefinite. For purposes of applying prior art, claim 55 is understood as follows: “wherein the anti-VEGF therapy comprises the administration of one or more antibodies selected from…”
Claims 2, 9, 14, 17, 48, 50, 52-55, 58, and 60 depend directly or indirectly from an indefinite base claim and fail to clarify the indefiniteness of the base claim. Accordingly, these claims are rejected as indefinite for the reasons applicable to the claim upon which they depend, as set forth above.
Accordingly, claims 1-2, 9, 14, 17, 39, 48, 50, 52-55, 58, and 60 are rejected.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 9, 14, 48 are each rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 9 depends from claim 1 and only differs from claim 1 by the recitation of an intended and expected result that would necessarily occur upon the successful completion of the active, “hand-of-man” steps recited in the body of claim 1. Per MPEP § 2111.04(I), “Claim scope is not limited by claim language that . . . . does not require steps to be performed, or by claim language that does not limit a claim to a particular structure”, and further states that a “whereby clause” in a claim “is not given weight when it simply expresses the intended result of a process step positively recited”. Here, the “wherein” clause does not unambiguously correspond to a clear structure/function relationship in the original disclosure, and therefore is not reasonably interpreted as a functional limitation requiring a particular subset of structures within the scope of claim 1. Rather, the “wherein” clause is understood to merely recite an intended or expected result fully satisfied by the positively recited steps and/or structures set forth in the body of the claim. Therefore, the “wherein” clause at claim 9 is understood to be fully satisfied by all prior art embodiments that satisfy the positively recited, active method steps set forth in the body of claim 1. Accordingly, claim 9 is rejected under 35 USC 112(d) for failing to further limit the scope of the claim upon which it depends.
Claim 14 depends from claim 1 and only differs from claim 1 by the recitation of an intended and expected result that would necessarily occur upon the successful completion of the active, “hand-of-man” steps recited in the body of claim 1. Per MPEP § 2111.04(I), “Claim scope is not limited by claim language that . . . . does not require steps to be performed, or by claim language that does not limit a claim to a particular structure”, and further states that a “whereby clause” in a claim “is not given weight when it simply expresses the intended result of a process step positively recited”. Here, the “wherein” clause does not unambiguously correspond to a clear structure/function relationship in the original disclosure, and therefore is not reasonably interpreted as a functional limitation requiring a particular subset of structures within the scope of claim 1. Rather, the “wherein” clause is understood to merely recite an intended or expected result fully satisfied by the positively recited steps and/or structures set forth in the body of the claim. Therefore, the “wherein” clause at claim 14 is understood to be fully satisfied by all prior art embodiments that satisfy the positively recited, active method steps set forth in the body of claim 1. Accordingly, claim 14 is rejected under 35 USC 112(d) for failing to further limit the scope of the claim upon which it depends.
Claim 48 depends from claim 1. Claim 1 recites a method wherein an “anti-VEGF agent” must necessarily and inherently be administered “before, during, or after provision of the AIBP composition” (see claim 1). Accordingly, as currently drafted, claim 48 simply reiterates the total inherent scope of claim 1, but fails to further limit the scope of claim 1 since claim 48 simply reiterates all possible scenarios inherently present at claim 1. Accordingly, claim 48 is rejected under 35 USC 112(d) for failing to further limit the scope of the claim upon which it depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 112(a), Written Description
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-2, 9, 14, 17, 39, 48, 50, 52-55, 58, and 60 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Brief Statement of the Issue(s)
The pending claims are directed to methods, involving the administration of a “therapeutically effective amount” or (“effective amount”) of a composition comprising an two functionally defined components (the fragment or derivative of AIBP, and an “anti-VEGF agent”), wherein the “therapeutically effective amount” is sufficient to treat “choroidal neovascularization” or overcome “resistance to an anti-VEGF therapy” (see claims 1 and 39); however, the description fails to provide a corresponding structure/function relationship for the functionally defined components commensurate in scope with the pending claims, and also fails to provide guidance regarding a “therapeutically effective amount” of such components.
Claim Scope
Claims 1 and 39 are representative of the pending claims scope and recite methods of administering a composition comprising AIBP (or a functionally active fragment or derivative thereof”), ApoA-1, and an anti-VEGF agent.
The phrase “AIBP or a functionally active fragment or derivative thereof” (see, e.g., claims 1 and 39) may potentially include (i) all peptides that share at least 90% identity with SEQ ID NO: 1 (i.e., >>100 trillions species)10, (ii) any peptide comprising “the N-terminus” of SEQ ID NO: 1 (i.e., any peptide comprising Methionine); (iii) any peptide comprising “the C-terminus” of SEQ ID NO: 1 (i.e., any peptide comprising a “Q” or Gln); (iv) any peptide that “comprises 1 . . . or more variations compared to SEQ ID NO: 1” (i.e., any peptide in existence differs by “1 or more variations” from any other peptide).
The phrase “anti-VEGF agent” is a functionally defined term that encompasses any structure (e.g., DNA aptamers, antisense agents, PNA, enzymes, peptides, antibodies, small molecules, etc., etc.) that reduces the activity of VEGF (see Spec. filed 11/18/2022 at ¶¶[0061]-[0062], instant claim 1).
The route of administration is unspecified and therefore encompasses all routes of administration, which include at least the composition may be administered intravitreally, intravenously, intradermally, intramuscularly, intraarterially, intrathecally, subcutaneous, or intraperitoneally (see Spec. filed 11/18/2022 at ¶¶[0100], instant claims 1, 39).
The “effective amount” or “therapeutically effective amount” is not specifically limited with respect to any specific combination of (a) ApoA-I with a (b) AIBP, AIBP fragment, AIBP or derivative, and (c) a particular anti-VEGF agent.
In addition, the applicable claim interpretations have been set forth above under 35 USC 112(b), (d), and in a separate claim interpretation section. Those discussions are incorporated herein.
It is unclear if the claim scope encompass trillions of species or perhaps only a few in view of the functional limitations set forth in the claim(s). Accordingly, the claim scope reasonably appears to be vast and highly varied.
Actual Reduction to Practice
The record appears to disclose one example reading upon the instant claim scope. Specifically, the originally filed disclosure teaches a laser-induced CNV mouse model with the AIBP of SEQ ID NO: 1, apoA-1 of SEQ ID NO: 3, and a single anti-VEGF antibody of AF-493-NA (see Spec. filed 11/18/2022 at ¶¶[0133]-[0135], Figures 15E and 21; see Reply filed 10/13/2025 at 9), wherein the components were administered via intravitreal injection11 at concentrations of 0.6-4.8µg of AIBP with a ratio of AIBP to ApoA-I of 1:4.2 (see Spec. filed 11/18/2022 at ¶[0133]).
Zero examples of the claimed methods utilizing any “fragment” or “derivative” of AIBP were reduced to practice or discussed with specificity.
Zero examples of the claimed methods utilizing any “anti-VEGF agents” within the class of DNA-aptamers, PNAs, antisense agents, antigene agents, small molecules, or non-antibody proteins were reduced to practice.
Zero examples of the claimed methods utilizing any route of administration other than intravitreal administration were reduced to practice.
Zero “therapeutically effective” or “effective” amounts were actually disclosed for any “fragment” or “derivative” of AIBP in combination with any “Anti-VEGF agent” other than AF-493-NA (see Spec. filed 11/18/2022 at ¶¶[0133]-[0135]).
Assessment of whether disclosed species are representative of the claimed genus
MPEP § 2163 states that a “representative number of species” means that the species which are adequately described are representative of the entire genus (see, e.g., MPEP § 2163(II)(3)(a), MPEP §2163.03(V)). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
As noted above, there is substantial variability in the claimed genus, which reads upon trillions of species differing by dosage, dosage frequency, administration route, patient population, AIBP structure (i.e., >>trillions), and Anti-VEGF structures (i.e., potentially infinite), etc.
However, only one example of the >>trillions of claimed species of method were reduced to practice, and zero variability was shown in AIBP structure, Anti-VEGF structures, administration routes, dosage, dosage frequencies, or patient populations.
Although the MPEP does not define what constitutes a sufficient number of representative species, the Courts have indicated that the disclosure of two species within a subgenus did not describe that subgenus. In re Gostelli, 872 F.2d at 1012, 10 USPQ2d at 1618. Similarly, the disclosure of, at best, one species of the claimed invention, does not provide sufficient disclosure to satisfy the written description requirement for the instantly claimed genus.
Identifying characteristics of the genus
In the absence of a reduction to practice of a representative number of species, the written description requirement for a claimed genus may be satisfied by disclosure of relevant, identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.
A simple threshold issue is whether or not an artisan could distinguish functionally active fragments or derivatives from non-functionally active fragments and derivatives, because the Courts have stated
“[r]egardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to the subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods.” University of Rochester v. G.D. Searle Co., 69 USPQ2d 1886 1984 (CAFC 2004) (emphasis added).
Upon reviewing the original disclosure, it is unclear how an artisan would reasonably distinguish infringing (i.e., “functional”) from non-infringing (i.e., non-functional) embodiments because the term “functionally active fragment or derivative” does not correspond to a structure/function relationship of record. Furthermore, the closest description of record is of the terms “functional” and “functionally equivalent derivative” (see Spec. filed 11/18/2022 at ¶[0079]), and the disclosure states
Whether or not a given polypeptide or polynucleotide is "functional" may be determined by first selecting an appropriate function to assess. For example, functionality of AIBP variants may be assessed in vitro or in vivo for the ability of the variants to attenuate neovascularization, for example, by improving removal of cholesterol from endothelial cells and/or macrophages, reducing inflammation, and/or restoring macrophages' ability to inhibit angiogenesis. Functionality of AIBP variants may also be assessed in vitro or in vivo for the ability of the variants to increase the efficacy of an anti-VEGF agent in inhibiting angiogenesis. In some cases, a functional molecule may be one that exhibits the desired function to a statistically significant degree (e.g. p<0.05; <0.01; <0.001).
Accordingly, a “functionally active fragment or derivative” is a functional limitation attempting to limit the scope of the claims unspecified structures having unspecified functions that Applicant desires and hopes to achieve, but fails to meaningfully provide guidance regarding a consensus structure reasonably permitting an artisan to distinguish functional and non-functional sequences from among the >>100’s of trillions of species presently claimed. Accordingly, the original disclosure fails to reasonably inform artisans of what structures do or do not satisfy the functional limitations of the pending claims.
A second, threshold question is whether or not the record reasonably informs artisans of what structures do or do not constitute an “Anti-VEGF agent” as presently claimed. Such language appears to be an attempt to “reach-through” and claim structures not yet discovered based upon a desired function. However, no consensus structure exists for the exemplified Anti-VEGF agents of record (see Spec. filed 11/18/2022 at ¶¶[0061]-[0062]). And no examples of Anti-VEGF agents falling within chemical classes such as DNA aptamers, PNAs, antisense agents, antigene agents, non-antibody proteins, etc. are disclosed or exemplified on record at all, but are presently encompassed by the language of the pending claims. As noted above, the Courts have stated
“[r]egardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to the subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods.” University of Rochester v. G.D. Searle Co., 69 USPQ2d 1886 1984 (CAFC 2004) (emphasis added).
This is pertinent because the “inventor cannot lay claim” to Anti-VEGF agents in the absence of a description sufficient to distinguish infringing compounds from non-infringing compounds. Here, there is no evidence currently of record reasonably identifying that general consensus structures of all possible “Anti-VEGF agents” were known in the prior art.
Accordingly, the functional limitations of the pending claims are only utilized as a vague attempt to capture unknown and undisclosed structures, sufficient to achieve some functional result that Applicant hopes and desires that the disclosed invention is able to achieve. However, the disclosure but does not meaningfully disclose an unambiguous structure/function relationship permitting an artisan to identify, a priori, which exact structures do or do not satisfy the functional limitations at issue.
Predictability in the Art
Although the level of skill in the art is high, the predictability in the art is low due to the complexity of biological systems, biochemistry, clinical variability of patient populations, dosages, dosage frequencies, administration routes, protein conformations, etc., etc. Specifically, an artisan would not be able to predict or identify, a priori, and in the absence of any guidance or consensus structures exactly what compounds would or would not constitute “a functionally active fragment or derivative” of AIBP, or otherwise what structures would be capable of functioning as a “anti-VEGF agent” as required by the claims.
Accordingly, in the absence of sufficient structure/function teachings identifying particular compounds capable of satisfying the functional limitations present in the pending claims, as required to practice the full scope of the claims, an artisan would not reasonably conclude that Applicant possessed the full scope of the broad and highly varied claim scope.
Conclusion
The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate."). The courts have stated that “merely drawing a fence around a perceived genus is not a description of the genus. One needs to show that one has truly invented the genus, i.e., that one has conceived and described sufficient representative species encompassing the breadth of the genus. Otherwise, one has only a research plan, leaving it to others to explore the unknown contours of the claimed genus” (see, e.g., AbbVie v. Janssen, 111 USPQ2d 1780 (Fed. Cir. 2014) at 1789). In addition, the Courts have stated
“[r]egardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to the subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods.” University of Rochester v. G.D. Searle Co., 69 USPQ2d 1886 1984 (CAFC 2004) (emphasis added).
This is pertinent because, in the instant case, Applicants have claimed a broad and highly varied genus comprising an unknown number of species defined by reference to one or more functional limitations; however, the originally filed disclosure has failed to identify any common structure/function relationship sufficient to permit an artisan to identify what structures are included or excluded by the claim scope. This also means that it is prima facie unclear what structures are infringe or do not infringe upon the pending claim scope.
In conclusion, for the reasons discussed above, the skilled artisan would not reasonably conclude that the inventor(s), at the time the application was filed, had possession of the full scope of the claimed invention.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-2, 9, 14, 17, 39, 48, 50, 52-55, 58, and 60 are rejected under 35 U.S.C. 103 as being unpatentable over US2018/0125948A1 (May 10, 2018) in view of ARVO201912 as evidenced by Fu13, and further in view of NP_000030.114 and NP_658985.215.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding rejections and also in a separate section above, and those discussions and interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
Regarding claims 1-2, 39, 60, and treatment of choroidal neovascularization (CNV) in Age-related Macular Degeneration (AMD) patients by intravitreal administration of Anti-VEGF agents, US’948 pertains to “compositions and methods for treating CNV, such as found in the wet form of AMD, in a human subject” (see, e.g., US’948 at ¶[0005]; see also id. at ¶¶[0003]-[0005], [0023]-[0025], [0163]-[0164]; compare id. with instant claims 1-2, 39, and 60). US’948 explains that the routine clinical treatment of CNV in AMD patients included intravitreal administration of anti-VEGF agents (i.e., VEGF inhibitors) (see, e.g., US’948 at ¶¶[0004], [0168]-[0169], [0173]). Regarding instant claims 9, 14, and intended or expected results of positively recited method steps, these claims differ from instant claim 1 by recitation of a “wherein” clause that does not require additional steps to be performed. Per MPEP § 2111.04(I), “Claim scope is not limited by claim language that . . . . does not require steps to be performed, or by claim language that does not limit a claim to a particular structure”, and further states that a “whereby clause” in a claim “is not given weight when it simply expresses the intended result of a process step positively recited”. Accordingly, claims 9 and 14 are understood to be obvious in view of the prior art for the reasons applied to claim 1, above. Regarding instant claim 17(a), 17(d), 55, and the specific anti-VEGF agent utilized in the treatment of CNV, US’948 identifies that the routine clinical treatment of CNV in AMD patients included intravitreal administration of anti-VEGF agents (i.e., VEGF inhibitors) (see, e.g., US’948 at ¶¶[0004], [0168]-[0169], [0173], claims 1 and 6). US’948 identifies multiple anti-VEGF agents known in the prior art, including antibodies targeting VEGF, such as ranibizumab or bevacizumab, proteins such as aflibercept or sFLT01, and generally teaches (see, e.g., US’948 at ¶¶[0020], [0022], [0337]-[0338], claims 1, 6-9, 12, and 16-18; compare id. with instant claims 1-2, 17(a), 39, and 60). Furthermore, US’948 reasonably informs artisans that Anti-VEGF treatment may occur prior to subsequent treatments for CNV, and/or that Anti-VEGF treatments may be made in combination with additional treatments (see, e.g., US’948 at claims 1, 6-9, 12, and 16-18, ¶¶[0086], [0337]-[0338]; compare id. with instant claim 17(d)). Regarding instant claim 39, 50, 53-54, and “anti-VEGF therapy in an individual”, including individuals determined to have a resistance to treatment with one or more VEGF inhibitors, US’948 identifies that “anti-VEGF therapy” was the routine clinical treatment of CNV in AMD patients known in the art, and that such treatment included intravitreal administration of anti-VEGF agents (i.e., VEGF inhibitors) (see, e.g., US’948 at ¶¶[0004], [0086], [0168]-[0169], [0173], claims 1 and 6). Furthermore, US’948 identifies that patient populations resistant to treatment with anti-VEGF agents were already known and recognized in the prior art (see, e.g., US’948 at ¶[0087]). Accordingly, both “anti-VEGF therapy” and methods of identifying patient populations “resistant” to anti-VEGF therapies were known in the prior art, and therefore do not weigh in favor of a determination of non-obviousness. Regarding instant claims 48 and administration of Anti-VEGF agents before or concurrently with additional treatments, US’948 reasonably informs artisans that Anti-VEGF treatment may occur prior to subsequent treatments for CNV, and/or that Anti-VEGF treatments may be made in combination with additional treatments (see, e.g., US’948 at claims 1, 6-9, 12, and 16-18, ¶¶[0086], [0337]-[0338]; compare id. with instant claims 17(d), 48). Regarding instant claims 52-53 and treatment of an individual “when the individual has one or more risk factors for developing resistance to one or more anti-VEGF agents”, the instant disclosure reasonably identifies that “risk factors for developing resistance” as instantly claimed broadly includes simply receiving anti-VEGF treatment for CNV and AMD, or otherwise having CNV (see Spec. filed 11/18/2022 at ¶¶[0003], [0007]; see also Claim interpretation section, above). Here, the prior art teaches that treatment of individuals with CNV and AMD using anti-VEGF agents is routine in the prior art (see, e.g., US’948 at ¶¶[0003]-[0005], [0023]-[0025], [0156]-[0158], [0163]-[0164]). Accordingly, the prior art is understood to necessarily satisfy the patient population limit recited at claim 52. Regarding instant claim 55 and administration of an anti-VEGF agent such as ranibizumab, bevacizumab, or aflibercept, claim 55 has been rejected as indefinite (see rejection above), and is interpreted herein to refer to an agent administered to a patient as part of “anti-VEGF therapy”. US’948 identifies that the routine clinical treatment of CNV in AMD patients included intravitreal administration of anti-VEGF agents (i.e., VEGF inhibitors) (see, e.g., US’948 at ¶¶[0004], [0168]-[0169], [0173], claims 1 and 6), and explicitly identifies the anti-VEGF agents of ranibizumab, bevacizumab, and aflibercept (see, e.g., US’948 at ¶¶[0020], [0022], [0337]-[0338], claims 1, 6-9, 12, and 16-18; compare id. with instant claims 1-2, 17(a), 39, and 60). Regarding instant claim 58, and intended or expected results of positively recited method steps, these claims differ from instant claim 39 and 50 by a recitation of a “wherein” clause that does not require additional steps to be performed, but merely recites a predicted and expected outcome satisfied by the administration of AIBP and an anti-VEGF agent (see, e.g., claim 58, noting that it does not recite ApoA-I). Per MPEP § 2111.04(I), “Claim scope is not limited by claim language that . . . . does not require steps to be performed, or by claim language that does not limit a claim to a particular structure”, and further states that a “whereby clause” in a claim “is not given weight when it simply expresses the intended result of a process step positively recited”. Accordingly, claim 58 is understood to be obvious in view of the prior art for the reasons applied to claims 1 and 38, above, wherein such limitation would necessarily be satisfied upon administration of AIBP, ApoA-I, and one or more anti-VEGF agents to a patient. Regarding claim 60 and the treatment of humans and animal models, US’948 identifies that laser-induced CNV animal models were known in the prior art based upon the known effects of laser photocoagulation (see, e.g., US’948 at ¶¶[0158]-[0160]). However, US’948 reasonably informs artisans that the disclosure and results are applicable to humans (see, e.g., US’948 at ¶¶[0005], [0086]-[0090]).
US’948 differs from the instant claims as follows: Although US’948 identifies that the routine clinical treatment of CNV in AMD patients included intravitreal administration of anti-VEGF agents, US’948 does not explicitly teach or disclose the additional administration of AIBP (instant SEQ ID NO: 1) and apoA-I (i.e., instant SEQ ID NO: 3) to such patients. Therefore, the issue is whether or not it would have been obvious to modify the routine “Anti-VEGF therapy” of the prior art by additionally administering AIBP and apoA-I to patients having CNV, with a reasonable expectation of success.
US’948 establishes the existence of an art-recognized need: US’948 explains that there is an art-recognized treatments involving anti-VEGF agents has limitations, and that there is a need improved treatments (see, e.g., US’948 at ¶¶[0004], [0163]-[0164]). Accordingly, one of skill in the art would be motivated to look for additional treatments permitting the treatment of CNV in AMD patients using reduced amounts of anti-VEGF agents.
ARVO2019 refers to the Association for Research in Vision and Ophthalmology (ARVO) conference in Canada from April 28 to May 2019, wherein research abstracts were presented (see, e.g., ARVO2019, passim). Fu is cited herein to evidence that the abstract “AIBP suppresses choroidal neovascularization (CNV) by enhancing cholesterol efflux” was presented at ARVO2019 between April 28 to May 2019 (see, e.g., Fu at abstract at page 4, noting the disclosure stating “This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 29 - May 2, 2019”). Regarding the instant claims and the administration of AIBP and apoA-I to individuals with CNV, ARVO2019 as evidenced by Fu informed artisans that “intravitreal delivery of AIBP and apoA-I robustly inhibits laser-induced CNV” in a mouse model of pathological angiogenesis (see, e.g., Fu at §§ “Purpose”, “Methods”, and “Results”). Accordingly, the prior art provides clear guidance informing artisans that CNV could be predictably and desirably treated by the intravitreal delivery of human recombinant AIBP and apoA-I (see id). Accordingly, the treatment of CNV by administering the combined agents of AIBP and apoA-I was known in the prior art, shown to be therapeutically effective, and such treatment would therefore be reasonably inferred to be useful in the treatment of CNV in humans, because laser-induced CNV was an art-recognized model for human CNV (see, e.g., US’948 at ¶¶[0158]-[0160]).
Regarding instant SEQ ID NO: 1 and SEQ ID NO: 3: Although ARVO2019 as evidenced by Fu is silent regarding the sequences associated with AIBP and ApoA-I, ARVO2019 as evidenced by Fu identifies that the proteins were “recombinant human AIBP and apoA-I” (see, e.g., Fu at § “Methods”). This is pertinent because an artisan, circa 2019, would readily appreciate that human apoA-I corresponded to the known sequence of NP_000030.1 (compare NP_000030.1 at 1, 3, and 5 with instant SEQ ID NO: 3, showing 100% identity). Furthermore, an artisan, circa 2019, would readily appreciate that human AIBP corresponded to the known sequence of NP_658985.2 (compare NP_658985.2 at 1, 4 at § Protein, and 5 with instant SEQ ID NO: 1, showing 100% identity). Therefore, in view of ARVO2019 as evidenced by Fu, NP_000030.1, and NP_658985.2, and artisan would readily appreciate and understand that the prior art reasonably informed artisans that the administration of human recombinant AIBP and apoA-I corresponding to instant SEQ ID NOs: 1 and 3, could be predictably and desirably administered to treat CNV, with the expectation that such intravitreal treatment would “robustly inhibit” CNV (see, e.g., Fu at §§ “Methods” and “Results”).
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s):
First, the invention is the obvious modification/improvement of the routine “anti-VEGF therapies” utilized in the prior art to treat CNV, such as found in the wet form of AMD, in human subjects, as taught by the primary reference, wherein the modification/improvement of the prior art therapy consists of adding the known technique of treating CNV by administering human human recombinant AIBP and apoA-I as disclosed and suggested in view of ARVO2019 as evidenced by Fu, wherein such modification/improvement would predictably result in a method of treating CNV (such as found in wet AMD) by administering anti-VEGF agents, human AIBP, and human apoA-I, wherein such modification/improvement would be expected and predicted to merely result in the outcome taught by the prior art, namely successful treatment of CNV, while advantageously permitting the use of a reduced amount of anti-VEGF agents (see, e.g., MPEP §§ 2143(I)(C), (D), (G)).
Second, per MPEP § 2144.06(I), "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). Likewise, here, it is obvious to combine known compositions taught for use in the prior art for treatment of CNV to form a third composition comprising each component (i.e., Anti-VEGF agents, human apoA-I, and human AIBP) useful for the very same purpose of treating CNV, because “the idea of combining them flows logically from their having been individually taught in the prior art."
Furthermore, each component was known in the prior art, and would merely be expected to perform its art-recognized and disclosed functions in combination as they do separately.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to combine and administer known components in known treatments to a known patient population via known routes of administration, in order to achieve the results taught and suggested by the prior art (i.e., treatment of CNV) with a reasonable expectation of success.
Accordingly, claims 1-2, 9, 14, 17, 39, 48, 50, 52-55, 58, and 60 are rejected.
Claims 1-2, 9, 14, 17, 39, 48, 50, 52-55, 58, and 60 are rejected under 35 U.S.C. 103 as being unpatentable over US2018/0125948A1 (May 10, 2018), ARVO2019 as evidenced by Fu, NP_000030.1 and NP_658985.2 as applied to claims 1-2, 9, 14, 17, 39, 48, 50, 52-55, 58, and 60 above, and further in view of US20170283502 A1 (Oct. 5, 2017).
Claim interpretation: The applicable claim interpretation has been set forth in a preceding rejections and also in a separate section above, and those discussions and interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
The teachings of US2018/0125948A1 (May 10, 2018), ARVO2019 as evidenced by Fu, NP_000030.1 and NP_658985.2 as applied to claims 1-2, 9, 14, 17, 39, 48, 50, 52-55, 58, and 60, have been set forth above, and those teachings are incorporated into the instant rejection.
The teachings of US’948, ARVO2019 as evidenced by Fu, NP_000030.1 and NP_658985.2, differ from the originally elected species as follows: Although US’948 teaches and discloses anti-VEGF agents, including antibodies such as ranibizumab and bevacizumab (see, e.g., US’948 at ¶¶[0020], [0022], [0337]-[0338]), the combination of references does not teach the anti-VEGF antibody utilized in the originally elected species, namely “AF-493-NA”16.
AF-493-NA is a prior art element: US’502 identifies that, circa 2017, AF-493-NA was a prior art element, namely an art-recognized anti-VEGF antibody (“VEGF neutralizing antibody”), usable in experiments on mice retinas involving intravitreally injections (see, e.g., US’502 at ¶¶[0135], [0265], [0289]). Accordingly, AF-493-NA was a prior art compound, identified as an anti-VEGF antibody and as a VEGF neutralizing antibody. This is pertinent because the primary reference identifies that an “Anti-VEGF” compound includes antibodies (see, e.g., US’948 at ¶¶[0020], [0337]-[0338], noting that the VEGF inhibitor may be “an antibody against VEGF”).
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s):
It would have been obvious to simply substitute one anti-VEGF antibody for another anti-VEGF antibody (e.g., AF-493-NA) into the methods and routine clinical treatment and animal model testing disclosed by the primary reference, because it amounts to the simple substitution of one “antibody against VEGF” for another “antibody against VEGF”, wherein such substitution would yield predictable results, namely an art-recognized equivalent antibody for purposes of binding VEGF following intravitreal injection, which would therefore be predicted and expected to act as an anti-VEGF agent in “anti-VEGF therapy” as taught and disclosed by the primary reference (see, e.g., MPEP § 2143(I)(B), § 2144.06(II); see also MPEP § 2144.07; see also Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327 (1945), at 335, explaining that "[r]eading a list and selecting a known compound to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle", wherein in the instant case reading and selecting a commercially available, art-recognized “antibody against VEGF” to act as an “antibody against VEGF” is likewise obvious).
Furthermore, as explained in the preceding rejection, each component was known in the prior art, and would merely be expected to perform its art-recognized and disclosed functions in combination as they do separately.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to combine and administer known components in known treatments to a known patient population via known routes of administration, in order to achieve the results taught and suggested by the prior art (i.e., treatment of CNV) with a reasonable expectation of success. In addition, it is well-within the ordinary skill in the art to review the prior art for an “antibody against VEGF” and to select prior art compounds identified as an “antibody against VEGF”, with the reasonable expectation that such compounds would act as an “antibody against VEGF”.
Accordingly, claims 1-2, 9, 14, 17, 39, 48, 50, 52-55, 58, and 60 are rejected.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RANDALL L BEANE whose telephone number is (571)270-3457. The examiner can normally be reached Mon.-Fri., 7 AM to 2 PM ET.
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/RANDALL L BEANE/Primary Examiner, Art Unit 1654
1 CNV occurs in “Wet AMD” and other diseases, including ocular histoplasmosis, angioid streaks, pathological myopia, and choroidal ruptures (see, e.g., Spec. filed 11/18/2022 at ¶[0003]).
2 see Spec. filed 11/18/2022 at ¶[0133]; see Reply filed 10/13/2025 at 9.
3 see Spec. filed 11/18/2022 at ¶[0064]; see Reply filed 10/13/2025 at 9.
4 see Spec. filed 11/18/2022 at ¶[0081].
5 see Spec. filed 11/18/2022 at ¶¶[0133], [0135], Figures 15E and 21; see Reply filed 10/13/2025 at 9, noting that no chemical structure or SEQ ID NO was provided for the Anti-VEGF agent, but that the Specification identifies it as AF-493-NA from R&D systems.
6 Association for Research in Vision and Ophthalmology (ARVO) conference in Canada from April 28 to May 2019, Schedule-at-a-glance, 1 page (2019).; hereafter “ARVO2019”.
7 Yingbin Fu et al., AIBP suppresses choroidal neovascularization (CNV) by enhancing cholesterol efflux. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3272, attached as 4 pages, also available at https://iovs.arvojournals.org/article.aspx?articleid=2743154 (last visited 12/5/2025); hereafter “Fu”.
8 AJ315849.1, NCBI.NLM.NIH.GOV, Homo sapiens mRNA for apoA-I binding protein (AIBP gene), NCBI GenBank: AJ315849.1 (PRI 07-OCT-2008), 3 pages also available at https://www.ncbi.nlm.nih.gov/nuccore/AJ315849 (last visited 12/05/2025).
9 NP_658985.2, ncbi.nlm.nih.gov, NAD(P)H-hydrate epimerase precursor [Homo sapiens], NCBI Protein Database Reference Sequence: NP_658985.2 (PRI-28-FEB-2019), 5 pages, also available at https://www.ncbi.nlm.nih.gov/protein/91984773?sat=47&satkey=5072574 (last visited 12/05/2025)
10 SEQ ID NO: 1 is understood to have 288 amino acids. Therefore, 90% identity encompasses species having 28 mutations or substitutions. Considering only the 20 proteinogenic amino acids, this includes at least 1928 species, or >>6.384e+35 different species
11 see Spec. filed 11/18/2022 at ¶[0133]; see Reply filed 10/13/2025 at 9.
12 Association for Research in Vision and Ophthalmology (ARVO) conference in Canada from April 28 to May 2019, Schedule-at-a-glance, 1 page (2019).; hereafter “ARVO2019”.
13 Yingbin Fu et al., AIBP suppresses choroidal neovascularization (CNV) by enhancing cholesterol efflux. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3272, attached as 4 pages, also available at https://iovs.arvojournals.org/article.aspx?articleid=2743154 (last visited 12/5/2025); hereafter “Fu”.
14 NP_000030.1, ncbi.nlm.nih.gov, apolipoprotein A-I isoform 1 preproprotein [Homo sapiens], NCBI Protein Database Reference Sequence: NP_000030.1 (PRI 25-FEB-2019), 5 pages, also available at https://www.ncbi.nlm.nih.gov/protein/4557321?sat=47&satkey=5065307 (last visited 12/05/2025)
15 NP_658985.2, ncbi.nlm.nih.gov, NAD(P)H-hydrate epimerase precursor [Homo sapiens], NCBI Protein Database Reference Sequence: NP_658985.2 (PRI-28-FEB-2019), 5 pages, also available at https://www.ncbi.nlm.nih.gov/protein/91984773?sat=47&satkey=5072574 (last visited 12/05/2025)
16 see Spec. filed 11/18/2022 at ¶¶[0133], [0135], Figures 15E and 21; see Reply filed 10/13/2025 at 9, noting that no chemical structure or SEQ ID NO was provided for the Anti-VEGF agent, but that the Specification identifies it as AF-493-NA from R&D systems.