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 .
Election/Restrictions
Claims 39 and 41 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 5/8/2026.
Claims 46 and 47 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 5/8/2026.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement(s) (IDS) was/were submitted on 5/6/2024 and 5/8/2026 before the mailing of a first office action. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Status
Claims 1-3, 6, 10, 13, 14, 18, 19, 25-27, 32, 34, 37, 39, 41, and 45-47 are pending. Claims 39, 41, 46, and 47 are withdrawn. Claims 1-3, 6, 10, 13, 14, 18, 19, 25-27, 32, 34, 37, and 45 are under examination.
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 3 and 6 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.
Regarding claim 3, claim 3 recites multiple embodiments of the first domain of the polypeptide chain of claim 1 listed with an “and/or” conjunction. It is not clear how the first domain can simultaneously be a variant of domain 2 of VEGFR-1 and also consist of the amino acid sequence of SEQ ID NO: 1 when SEQ ID NO: 1 is domain 2 of VEGFR-1.
Consequently, claim 3 is rejected.
Regarding claim 6, claim 6 recites multiple embodiments of the second domain of the polypeptide chain of claim 1 listed with an “and/or” conjunction. It is not clear how the first domain can simultaneously be a variant of domain 3 of VEGFR-2 and also consist of the amino acid sequence of SEQ ID NO: 2 when SEQ ID NO: 2 is domain 3 of VEGFR-2.
Consequently, claim 6 is rejected.
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 1-3, 6, 10, 13, 14, 18, 19, 25-27, 32, 34, 37, and 45 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.
Regarding claim 1, claim 1 recites: “A polypeptide comprising: (i) a first domain that binds to VEGF; (ii) a second domain that binds to VEGF; and (iii) a third domain that binds to an angiopoietin.”
This claim encompasses multiple open-ended genera; namely, any two domains that bind to VEGF and a third domain that binds to angiopoietin. These domains encompass essentially unlimited sequence space.
In this case, the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. (MPEP § 2163 (II.A.3.a.ii.))
According to MPEP § 2163 (II.A.3.a.ii.), a "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014).
Claim 1 contains no limitations on the domains that must be able to bind to VEGF and angiopoietin. Consequently, the claim is extremely broad.
MPEP § 2163 (II.A.3.a.ii.) states that “for inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are ‘representative of the full variety or scope of the genus,’ or by the establishment of ‘a reasonable structure-function correlation.’”
Even when several species are disclosed, these are not necessarily representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (“The ’128 and ’485 patents, however, only describe species of structurally similar antibodies that were derived from Joe-9. Although the number of the described species appears high quantitatively, the described species are all of the similar type and do not qualitatively represent other types of antibodies encompassed by the genus.”). Thus, when there is substantial variation within the genus, as here, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. Since each genus recited in the instant claims is large, it would be very challenging to describe sufficient species to cover the structures of the entire genus.
In the instant case, Applicant reduces thirteen polypeptides to practice that utilize a subset of these claimed domains. For example, four distinct angiopoietin domains appear to be reduced to practice which are used in various polypeptides.
At the time the invention was made, the level of skill for preparing and screening polypeptides with desired functional properties was high. However, even if a synthesis and selection procedure was, at the time of the invention, sufficient to enable the skilled artisan to identify polypeptides with the recited properties, the written description provision of 35 U.S.C § 112 is severable from its enablement provision. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336 (Fed. Cir. 2010); see also Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1876 (Fed. Cir. 2011) (“The fact that a fully-human antibody could be made does not suffice to show that the inventors of the '775 patent possessed such an antibody.”) Absent the conserved structure provided by the provided species, the skilled artisan generally would not be able to visualize or otherwise predict, a priori, what polypeptide with a particular set of properties would look like structurally.
Applicant provides thirteen exemplary polypeptides that utilize a finite number of VEGF and angiopoietin domains, for example the four angiopoietin domains described above.
The provided examples only represent a limited structural diversity. Since only a limited number of species of peptides are taught within the claimed genus above, the instant claim above fails the written description requirement. A representative number of species has not been taught to describe this genus. Regarding the peptides, a single point mutation can change the biophysical properties of a peptide: “In summary, we have shown that the structural changes in the fibrillar state of the Aβ42 peptide that are observed to occur upon introduction of single point mutations can be accompanied by changes in the dominance of the microscopic processes by which these aggregates are themselves formed.” (Bolognesi et al. ACS Chem Bio 9:2 (2013) page 381 col. 2 para. 3) and “In summary, while ovispirin-1 and novispirin G-10 both had solution structures that were helical and amphipathic in the presence of TFE, a relatively simple change in their primary structure (a single glycine–isoleucine exchange) had profound effects on their respective toxicities for human erythrocytes and epithelial cells.” (Sawai et al. Protein Eng. 15:3 (2002) page 232 col. 1 para. 3).
Furthermore, many sequences allowed by the current scope of the claims, result in non-functional aggregates. Wang (Wang, et al. MAbs. Vol. 1. No. 3. Taylor & Francis, (2009)) discloses a variety of aggregation prone motifs that occur in commercial antibodies (Wang, page 262, Table 2). The scope of the claims currently may incorporate such motifs and result in non-functional aggregates.
Given this unpredictability of protein design, the skilled artisan would not have been in possession of the substantial repertoire of peptide species encompassed by the claimed invention; one of skill in the art would conclude that applicant was not in possession of the structural attributes of a representative number of species possessed by the members of the genus of every peptide molecule recited by claim 1. One of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genus. Therefore, claim 1 is rejected.
Regarding claim 2, claim 1 is rejected as described above. Claim 2 does not reduce the genus size of claim 1. One of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genus.
Therefore, claim 2 is rejected.
Regarding claim 3, claim 1 is rejected as described above. Claim 3 further recites: “The polypeptide of claim 1, wherein the first domain: (i) is derived from VEGF receptor-1 (VEGFR-1 or FLT-1); (ii) comprises domain 2 of VEGFR-1 or a variant thereof; (iii) comprises or consists of an amino acid sequence of SEQ ID NO: 1; and/or (iv) comprises or consists of an amino acid sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identity to SEQ ID NO: 1.”
This claim allows for 0.2*103 = 20 substitutions, which allows for 20^20 genus members, just from the first VEGF binding domain alone. This claim does not sufficiently reduce the size of the claimed genus of claim 1 and one of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genus
Consequently, claim 3 is rejected.
Regarding claim 6, claim 1 is rejected as described above. This claim allows for 0.2*101 = 20 substitutions, which allows for 20^20 genus members, just from the second VEGF binding domain alone. This claim does not sufficiently reduce the size of the claimed genus of claim 1 and one of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genus
Consequently, claim 6 is rejected.
Regarding claim 10, claim 1 is rejected as described above. This claim allows for 0.2*59 = 11 substitutions, which allows for 20^11 genus members, just from the third domain alone. This claim does not sufficiently reduce the size of the claimed genus of claim 1 and one of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genus
Consequently, claim 10 is rejected.
Regarding claim 13, claim 1 is rejected as described above. This claim allows for 0.2*103 = 20 substitutions of SEQ ID NO: 1, which allows for 20^20 genus members, just from the first VEGF binding domain alone. This claim does not sufficiently reduce the size of the claimed genus of claim 1 and one of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genus
Consequently, claim 13 is rejected.
Regarding claim 14, claim 1 is rejected as described above. This claim further limits claim 1 by adding additional regions to the polypeptide and does not reduce the size of the claimed genus. One of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genus
Consequently, claim 14 is rejected.
Regarding claim 18, claim 1 is rejected as described above. This claim allows for 0.2*742 = 148 substitutions of SEQ ID NO: 65, which allows for 20^148 genus members. This claim does not sufficiently reduce the size of the claimed genus of claim 1 and one of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genus.
Consequently, claim 18 is rejected.
Regarding claim 19, claim 1 is rejected as described above. This claim further limits claim 1 by adding additional regions to the polypeptide and does not reduce the size of the claimed genus. One of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genus.
Consequently, claim 19 is rejected.
Regarding claim 25, claim 1 is rejected as described above. Claim 25 introduces an agent conjugated to the polypeptide of claim 1 and does not reduce the size of the claimed genus. One of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genus.
Consequently, claim 25 is rejected.
Regarding claim 26, claim 1 is rejected as described above. A nucleic acid encoding such a huge genus size will have a similar genus size and only thirteen nucleic acid sequences are reduced to practice. One of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genus.
Consequently, claim 26 is rejected.
Regarding claims 27, 32, and 34, these nucleic acid claims have at least the same genus size as claim 26. One of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genus for these claims.
Consequently, claims 27, 32, and 34 are rejected.
Regarding claim 37, this claim allows for 0.2*3672 = 734 substitutions of SEQ ID NO: 65, which allows for 4^148 genus members. The number of nucleic acids reduced to practice and recited by the specification is not representative of the size of this genus. One of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genus.
Consequently, claim 37 is rejected.
Regarding claim 45, claim 1 is rejected as described above. Claim 45 introduces a pharmaceutically acceptable excipient to the polypeptide of claim 1 and does not reduce the size of the claimed genus. One of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genus.
Consequently, claim 45 is rejected.
Claim Rejections - 35 USC § 102
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 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.
Claims 1-3, 6, 10, 13, 14, 18, 25, 26, and 45 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lu et al. US 20170327569, published 11/16/2017.
Regarding claim 1, claim 1 recites: “A polypeptide comprising: (i) a first domain that binds to VEGF; (ii) a second domain that binds to VEGF; and (iii) a third domain that binds to an angiopoietin.”
Claim 1 of Lu discloses:
“ A chimeric molecule comprising:
a. an anti-VEGF antibody or a VEGF receptor-Fc-fusion; and
b. a peptide that binds to angiopoietin 2 (Ang2);
c. wherein the peptide that binds to Ang2 comprises a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO:1; and
d. wherein the chimeric molecule inhibits the binding of VEGF to a VEGF receptor and inhibits binding of Ang2 to an Ang2 receptor.”
Notably, the VEGF receptor-Fc-fusion may be afilbercept, which has an amino acid sequence as shown in Lu SEQ ID NO:5. This Fc-fusion is disclosed as having two VEGF binding domains: “Aflibercept is a recombinant fusion protein consisting of VEGF-binding portions from the extracellular domains of human VEGF receptors 1 and 2, that are fused to the Fc portion of the human IgG1 immunoglobulin.” (Lu, et al., para. [0007] and [0049]).
Consequently, claim 1 is anticipated by Lu et al. and rejected.
Regarding claim 2, claim 1 is anticipated as described above. Claim 2 further recites the case wherein the third domain is at the N- terminus of the first domain and the second domain.
Lu discloses that the Ang-2 (angiopoietin) domain can be fused to the N-terminal of the VEGF binding domain:
“A chimeric molecule, which comprises an antibody and an Ang2 binding peptide, wherein said peptide is fused to the N-terminus or C-terminus of the light chains and/or heavy chains of said antibody, optionally with a peptide linker, wherein the peptide has an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity to a peptide selected from the group consisting of SEQ ID NOS:7-12, and wherein said antibody binds to VEGF.” (Lu et al., claim 17).
Regarding claim 3, claim 1 is anticipated as described above. Lu discloses SEQ ID NO: 6, aligned against Applicant SEQ ID NO: 1 below:
#=======================================
#
# Aligned_sequences: 2
# 1:
# 2:
# Matrix: EBLOSUM62
# Gap_penalty: 10.0
# Extend_penalty: 0.5
#
# Length: 517
# Identity: 103/517 (19.9%)
# Similarity: 103/517 (19.9%)
# Gaps: 414/517 (80.1%)
# Score: 544.0
#
#
#=======================================
1 MVSYWDTGVLLCALLSCLLLTGSSSGSDTGRPFVEMYSEIPEIIHMTEGR 50
||||||||||||||||||||||||
1 --------------------------SDTGRPFVEMYSEIPEIIHMTEGR 24
51 ELVIPCRVTSPNITVTLKKFPLDTLIPDGKRIIWDSRKGFIISNATYKEI 100
||||||||||||||||||||||||||||||||||||||||||||||||||
25 ELVIPCRVTSPNITVTLKKFPLDTLIPDGKRIIWDSRKGFIISNATYKEI 74
101 GLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLSPSHGIELSVGEKLVLNC 150
|||||||||||||||||||||||||||||
75 GLLTCEATVNGHLYKTNYLTHRQTNTIID--------------------- 103
151 TARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDG 200
103 -------------------------------------------------- 103
201 VTRSDQGLYTCAASSGLMTKKNSTFVRVHEKDKTHTCPPCPAPELLGGPS 250
103 -------------------------------------------------- 103
251 VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKT 300
103 -------------------------------------------------- 103
301 KPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA 350
103 -------------------------------------------------- 103
351 KGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN 400
103 -------------------------------------------------- 103
401 NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK 450
103 -------------------------------------------------- 103
451 SLSLSPGKGGGGGAQQEECEWDPWTCEHMGSGSATGGSGSTASSGSGSAT 500
103 -------------------------------------------------- 103
501 HQEECEWDPWTCEHMLE 517
103 ----------------- 103
Consequently, claim 3 is anticipated by Lu et al. and rejected.
Regarding claim 6, claim 1 is anticipated as described above. Lu discloses SEQ ID NO: 6, aligned against Applicant SEQ ID NO: 2 below:
#=======================================
#
# Aligned_sequences: 2
# 1:
# 2:
# Matrix: EBLOSUM62
# Gap_penalty: 10.0
# Extend_penalty: 0.5
#
# Length: 517
# Identity: 101/517 (19.5%)
# Similarity: 101/517 (19.5%)
# Gaps: 416/517 (80.5%)
# Score: 520.0
#
#
#=======================================
1 MVSYWDTGVLLCALLSCLLLTGSSSGSDTGRPFVEMYSEIPEIIHMTEGR 50
0 -------------------------------------------------- 0
51 ELVIPCRVTSPNITVTLKKFPLDTLIPDGKRIIWDSRKGFIISNATYKEI 100
0 -------------------------------------------------- 0
101 GLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLSPSHGIELSVGEKLVLNC 150
|||||||||||||||||||||
1 -----------------------------VVLSPSHGIELSVGEKLVLNC 21
151 TARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDG 200
||||||||||||||||||||||||||||||||||||||||||||||||||
22 TARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDG 71
201 VTRSDQGLYTCAASSGLMTKKNSTFVRVHEKDKTHTCPPCPAPELLGGPS 250
||||||||||||||||||||||||||||||
72 VTRSDQGLYTCAASSGLMTKKNSTFVRVHE-------------------- 101
251 VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKT 300
101 -------------------------------------------------- 101
301 KPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA 350
101 -------------------------------------------------- 101
351 KGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN 400
101 -------------------------------------------------- 101
401 NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK 450
101 -------------------------------------------------- 101
451 SLSLSPGKGGGGGAQQEECEWDPWTCEHMGSGSATGGSGSTASSGSGSAT 500
101 -------------------------------------------------- 101
501 HQEECEWDPWTCEHMLE 517
101 ----------------- 101
Consequently, claim 6 is anticipated by Lu et al. and rejected.
Regarding claim 10, claim 1 is anticipated as described above. Lu discloses SEQ ID NO: 6, which is aligned against Applicant SEQ ID NO: 3 below:
#=======================================
#
# Aligned_sequences: 2
# 1:
# 2:
# Matrix: EBLOSUM62
# Gap_penalty: 10.0
# Extend_penalty: 0.5
#
# Length: 517
# Identity: 14/517 ( 2.7%)
# Similarity: 14/517 ( 2.7%)
# Gaps: 503/517 (97.3%)
# Score: 96.0
#
#
#=======================================
1 MVSYWDTGVLLCALLSCLLLTGSSSGSDTGRPFVEMYSEIPEIIHMTEGR 50
0 -------------------------------------------------- 0
51 ELVIPCRVTSPNITVTLKKFPLDTLIPDGKRIIWDSRKGFIISNATYKEI 100
0 -------------------------------------------------- 0
101 GLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLSPSHGIELSVGEKLVLNC 150
0 -------------------------------------------------- 0
151 TARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDG 200
0 -------------------------------------------------- 0
201 VTRSDQGLYTCAASSGLMTKKNSTFVRVHEKDKTHTCPPCPAPELLGGPS 250
0 -------------------------------------------------- 0
251 VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKT 300
0 -------------------------------------------------- 0
301 KPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA 350
0 -------------------------------------------------- 0
351 KGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN 400
0 -------------------------------------------------- 0
401 NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK 450
0 -------------------------------------------------- 0
451 SLSLSPGKGGGGGAQQEECEWDPWTCEHMGSGSATGGSGSTASSGSGSAT 500
||||||||||||||
1 ---------------QEECEWDPWTCEHM--------------------- 14
501 HQEECEWDPWTCEHMLE 517
14 ----------------- 14
Consequently, claim 10 is anticipated by Lu et al. and rejected.
Regarding claim 13, Applicant SEQ ID NOs 1, 2 and 3 are all part of SEQ ID NO: 7 as shown below:
#=======================================
#
# Aligned_sequences: 2
# 1:
# 2:
# Matrix: EBLOSUM62
# Gap_penalty: 10.0
# Extend_penalty: 0.5
#
# Length: 517
# Identity: 204/517 (39.5%)
# Similarity: 204/517 (39.5%)
# Gaps: 313/517 (60.5%)
# Score: 1064.0
#
#
#=======================================
1 MVSYWDTGVLLCALLSCLLLTGSSSGSDTGRPFVEMYSEIPEIIHMTEGR 50
||||||||||||||||||||||||
1 --------------------------SDTGRPFVEMYSEIPEIIHMTEGR 24
51 ELVIPCRVTSPNITVTLKKFPLDTLIPDGKRIIWDSRKGFIISNATYKEI 100
||||||||||||||||||||||||||||||||||||||||||||||||||
25 ELVIPCRVTSPNITVTLKKFPLDTLIPDGKRIIWDSRKGFIISNATYKEI 74
101 GLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLSPSHGIELSVGEKLVLNC 150
||||||||||||||||||||||||||||||||||||||||||||||||||
75 GLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLSPSHGIELSVGEKLVLNC 124
151 TARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDG 200
||||||||||||||||||||||||||||||||||||||||||||||||||
125 TARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDG 174
201 VTRSDQGLYTCAASSGLMTKKNSTFVRVHEKDKTHTCPPCPAPELLGGPS 250
||||||||||||||||||||||||||||||
175 VTRSDQGLYTCAASSGLMTKKNSTFVRVHE-------------------- 204
251 VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKT 300
204 -------------------------------------------------- 204
301 KPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA 350
204 -------------------------------------------------- 204
351 KGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN 400
204 -------------------------------------------------- 204
401 NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK 450
204 -------------------------------------------------- 204
451 SLSLSPGKGGGGGAQQEECEWDPWTCEHMGSGSATGGSGSTASSGSGSAT 500
204 -------------------------------------------------- 204
501 HQEECEWDPWTCEHMLE 517
204 ----------------- 204
########################################
# Program: needle
# Rundate: Wed 15 Jul 2026 22:29:45
# Commandline: needle
# -auto
# -asequence /var/lib/emboss-explorer/output/729778/.asequence
# -bsequence /var/lib/emboss-explorer/output/729778/.bsequence
# -noendweight
# -brief
# -outfile outfile
# -aformat3 srspair
# Align_format: srspair
# Report_file: outfile
########################################
#=======================================
#
# Aligned_sequences: 2
# 1:
# 2:
# Matrix: EBLOSUM62
# Gap_penalty: 10.0
# Extend_penalty: 0.5
#
# Length: 517
# Identity: 14/517 ( 2.7%)
# Similarity: 14/517 ( 2.7%)
# Gaps: 503/517 (97.3%)
# Score: 96.0
#
#
#=======================================
1 MVSYWDTGVLLCALLSCLLLTGSSSGSDTGRPFVEMYSEIPEIIHMTEGR 50
0 -------------------------------------------------- 0
51 ELVIPCRVTSPNITVTLKKFPLDTLIPDGKRIIWDSRKGFIISNATYKEI 100
0 -------------------------------------------------- 0
101 GLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLSPSHGIELSVGEKLVLNC 150
0 -------------------------------------------------- 0
151 TARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDG 200
0 -------------------------------------------------- 0
201 VTRSDQGLYTCAASSGLMTKKNSTFVRVHEKDKTHTCPPCPAPELLGGPS 250
0 -------------------------------------------------- 0
251 VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKT 300
0 -------------------------------------------------- 0
301 KPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA 350
0 -------------------------------------------------- 0
351 KGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN 400
0 -------------------------------------------------- 0
401 NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK 450
0 -------------------------------------------------- 0
451 SLSLSPGKGGGGGAQQEECEWDPWTCEHMGSGSATGGSGSTASSGSGSAT 500
||||||||||||||
1 ---------------QEECEWDPWTCEHM--------------------- 14
501 HQEECEWDPWTCEHMLE 517
14 ----------------- 14
Lu et al. discloses SEQ ID NO: 6, aligned against Applicant SEQ ID NO: 7 below:
SQ Sequence 491 AA;
Query Match 95.2%; Score 2651; Length 491;
Best Local Similarity 100.0%;
Matches 491; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 27 SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGKRIIWDS 86
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGKRIIWDS 60
Qy 87 RKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLSPSHGIELSVGEKL 146
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLSPSHGIELSVGEKL 120
Qy 147 VLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQ 206
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 VLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQ 180
Qy 207 GLYTCAASSGLMTKKNSTFVRVHEKDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR 266
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GLYTCAASSGLMTKKNSTFVRVHEKDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR 240
Qy 267 TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLN 326
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLN 300
Qy 327 GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPS 386
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPS 360
Qy 387 DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNH 446
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNH 420
Qy 447 YTQKSLSLSPGKGGGGGAQQEECEWDPWTCEHMGSGSATGGSGSTASSGSGSATHQEECE 506
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 YTQKSLSLSPGKGGGGGAQQEECEWDPWTCEHMGSGSATGGSGSTASSGSGSATHQEECE 480
Qy 507 WDPWTCEHMLE 517
|||||||||||
Db 481 WDPWTCEHMLE 491
Due to the comprising transitional phrase, this sequence reads on the polypeptide claimed in claim 13.
Consequently, claim 13 is anticipated by Lu et al. and rejected.
Regarding claim 14, claim 1 is anticipated as described above. Lu discloses that the polypeptide may have linkers:
“ A chimeric molecule, which comprises an antibody and an Ang2 binding peptide, wherein said peptide is fused to the N-terminus or C-terminus of the light chains and/or heavy chains of said antibody, optionally with a peptide linker, wherein the peptide has an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity to a peptide selected from the group consisting of SEQ ID NOS:7-12, and wherein said antibody binds to VEGF.” (Lu et al, claim 17).
Consequently, claim 14 is anticipated by Lu et al. and rejected.
Regarding claim 18, Lu et al. discloses SEQ ID NO: 6, aligned against Applicant SEQ ID NO: 7 below:
SQ Sequence 491 AA;
Query Match 95.2%; Score 2651; Length 491;
Best Local Similarity 100.0%;
Matches 491; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 27 SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGKRIIWDS 86
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGKRIIWDS 60
Qy 87 RKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLSPSHGIELSVGEKL 146
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLSPSHGIELSVGEKL 120
Qy 147 VLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQ 206
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 VLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQ 180
Qy 207 GLYTCAASSGLMTKKNSTFVRVHEKDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR 266
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GLYTCAASSGLMTKKNSTFVRVHEKDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR 240
Qy 267 TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLN 326
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLN 300
Qy 327 GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPS 386
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPS 360
Qy 387 DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNH 446
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNH 420
Qy 447 YTQKSLSLSPGKGGGGGAQQEECEWDPWTCEHMGSGSATGGSGSTASSGSGSATHQEECE 506
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 YTQKSLSLSPGKGGGGGAQQEECEWDPWTCEHMGSGSATGGSGSTASSGSGSATHQEECE 480
Qy 507 WDPWTCEHMLE 517
|||||||||||
Db 481 WDPWTCEHMLE 491
Consequently, claim 18 is anticipated by Lu et al. 2 and rejected.
Regarding claim 25, claim 1 is anticipated as described above. Lu discloses that the polypeptide may comprise additional agents:
“The term “formulation” as used herein refers to the fusion proteins disclosed herein and excipients combined together which can be administered and has the ability to bind to the corresponding receptors and initiate a signal transduction pathway resulting in the desired activity. The formulation can optionally comprise other agents so long as the fusion protein retains the ability to bind the corresponding receptors.” (Lu et al., para. [0106]).
Consequently, claim 25 is anticipated by Lu et al. and rejected.
Regarding claim 26, claim 1 is anticipated as described above. Lu discloses a polynucleotide encoding the polypeptide that reads on Applicant claim 1:
“10. Polynucleotides encoding the chimeric molecules of claim 1.” (Lu et al., claim 10).
Consequently, claim 26 is anticipated by Lu et al. and rejected.
Regarding claim 45, claim 1 is anticipated as described above. Lu discloses the usage of excipients: “The present specification also provides a pharmaceutical composition for the administration to a subject. The pharmaceutical composition disclosed herein may further include a pharmaceutically acceptable carrier, excipient, or diluent.” (Lu et al., para. [0107]).
Consequently, claim 45 is anticipated by Lu et al. and rejected.
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.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Lu, et al. US 20170327569, published 11/16/2017, in view of Gerometta et al. US 9,745,558, published 8/29/2017 and Duivelshof et al. (Duivelshof, et al. Journal of separation science 44.1: 35-62 (2020)).
Regarding claim 19, claim 1 is rejected as described above. Lu does not disclose an additional VEGFR-3 domain.
However, Duivelshof discloses the strategy of increasing avidity for fusion peptides: “Peptibodies are chimeric proteins consisting of a biologically active peptide conjugated to an Fc-domain of IgG [147]. Conjugation to the Fc-domain provides to the active peptide an extended half-life via FcRn-mediated recycling and reduced renal clearance [2]. Moreover, by conjugating multiple peptides to a single Fc-domain the avidity is increased and a higher clinical efficacy can be obtained.” (Duivelshof et al., page 53, col. 2, para. 2).
Such a strategy can be executed with the polypeptide of Lu by adding another VEGF binding domain, such as SEQ ID NO: 3 of Gerometta, aligned against Applicant SEQ ID NO: 56 below.
Gerometta et al. discloses: “In another aspect, the purified or isolated ligand binding molecule comprises amino acids 22-290 of SEQ ID NO: 3, amino acids 23-290 of SEQ ID NO: 3, amino acids 23-537 of SEQ ID NO: 3 or amino acids 22-537 of SEQ ID NO: 3. In still other variations, the molecule comprises an amino acid sequence at least 80%, or at least 85%, or at least 90%, or at least 92%, or at least 95%, or at least 96%, or at least 97%, or at least 98%, or at least 99% identical to either of the foregoing sequences, with the proviso that the sequence of the polypeptide that corresponds to (aligns with) the VEGFR-3 N2 sequon is not a glycosylation sequence.” (Gerometta et al., col. 6, line 50).
Query Match 100.0%; Score 1100; Length 537;
Best Local Similarity 100.0%;
Matches 202; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 YSMTPPTLNITEESHVIDTGDSLSISCRGQHPLEWAWPGAQEAPATGDKDSEDTGVVRDC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 YSMTPPTLNITEESHVIDTGDSLSISCRGQHPLEWAWPGAQEAPATGDKDSEDTGVVRDC 60
Qy 61 EGTDARPYCKVLLLHEVHAQDTGSYVCYYKYIKARIEGTTAASSYVFVRDFEQPFINKPD 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 EGTDARPYCKVLLLHEVHAQDTGSYVCYYKYIKARIEGTTAASSYVFVRDFEQPFINKPD 120
Qy 121 TLLVNRKDAMWVPCLVSIPGLNVTLRSQSSVLWPDGQEVVWDDRRGMLVSTPLLHDALYL 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 TLLVNRKDAMWVPCLVSIPGLNVTLRSQSSVLWPDGQEVVWDDRRGMLVSTPLLHDALYL 180
Qy 181 QCETTWGDQDFLSNPFLVHITG 202
||||||||||||||||||||||
Db 181 QCETTWGDQDFLSNPFLVHITG 202
It would have been obvious to a person of ordinary skill in the art before the effective filing date to add a VEGFR-3 binding domain as disclosed by Gerometta to the polypeptide of Lu to arrive at the claimed invention because Duivelshof discloses that avidity is known strategy for fusion polypeptides.
A person of ordinary skill in the art would be motivated to add this additional domain to increase the avidity to achieve more effective binding of the polypeptide to VEGF targets.
A person of ordinary skill in the art would have a reasonable expectation of success because Gerometta discloses that SEQ ID NO: 3 binds to VEGFR-3 and Duivelshof discloses the strategy of avidity for modulating fusion polypeptide affinity.
Consequently, claim 19 is obvious over Lu et al. in view of Duivelshof et al. and Gerometta et al. and rejected.
Claims 27, 32, and 34 are rejected under 35 U.S.C. 103 as being unpatentable over Lu, et al. US 20170327569, published 11/16/2017, in view of Earley et al. (Earley, et al. Human gene therapy 31.3-4: 151-162 (2020)).
Regarding claim 27, claim 26 is anticipated as described above. Lu does not specifically disclose an AAV vector that comprises the isolated nucleic acid of claim 26.
However, Earley discloses that AAV2 vectors are frequently used for gene delivery: “Currently, recombinant AAV (rAAV) vector production platforms rely on an AAV2 Rep—AAV2 ITR replication and packaging system.” (Earley et al., page 153, col. 1, para. 2).
Furthermore, Earley discloses that AAV vectors with AAV2 ITR regions have a high yield of proteins: “Under the conditions used here, all ITRs tested were capable of promoting transgene expression both in vitro and in vivo. However, we observed three classes of AAV ITR expression in vitro. Class I ITRs (AAV2 and 3) generated the highest level, whereas class II (AAV 4) had intermediate levels, and class III (AAV1 and 6) had the lowest levels. These expression levels were consistent across multiple cell lines.” (Earley, Abstract).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the AAV2 system disclosed by Earley to express the polypeptide encoded by the nucleic acid of Lu to arrive at the claimed invention because Earley discloses that AAV2 is a standard in this area of science.
A person of ordinary skill in the art would be motivated to use AAV2 vectors in order to perform gene delivery as disclosed by Earley.
A person of ordinary skill in the art would have a reasonable expectation of success because Earley discloses that these vectors have a high yield and are frequently used in this role.
Consequently, claim 27 is obvious over Lu et al. in view of Earley et al. and rejected.
Regarding claim 32, Lu discloses a polynucleotide as recited by claim 32 as described above for claim 26 above: “10. Polynucleotides encoding the chimeric molecules of claim 1.” (Lu et al., claim 10).
Furthermore, claim 1 of Lu discloses:
“ A chimeric molecule comprising:
a. an anti-VEGF antibody or a VEGF receptor-Fc-fusion; and
b. a peptide that binds to angiopoietin 2 (Ang2);
c. wherein the peptide that binds to Ang2 comprises a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO:1; and
d. wherein the chimeric molecule inhibits the binding of VEGF to a VEGF receptor and inhibits binding of Ang2 to an Ang2 receptor.”
Notably, the VEGF receptor-Fc-fusion may be afilbercept, which has an amino acid sequence as shown in Lu SEQ ID NO:5. This Fc-fusion is disclosed as having two VEGF binding domains: “Aflibercept is a recombinant fusion protein consisting of VEGF-binding portions from the extracellular domains of human VEGF receptors 1 and 2, that are fused to the Fc portion of the human IgG1 immunoglobulin.” (Lu, et al., para. [0007] and [0049]).
Lu does not disclose the case wherein the nucleic acid is in an AAV vector with ITRs present.
However, Earley discloses that AAV2 vectors are frequently used for gene delivery: “Currently, recombinant AAV (rAAV) vector production platforms rely on an AAV2 Rep—AAV2 ITR replication and packaging system.” (Earley et al., page 153, col. 1, para. 2).
Furthermore, Earley discloses that AAV vectors with AAV2 ITR regions have a high yield of proteins: “Under the conditions used here, all ITRs tested were capable of promoting transgene expression both in vitro and in vivo. However, we observed three classes of AAV ITR expression in vitro. Class I ITRs (AAV2 and 3) generated the highest level, whereas class II (AAV 4) had intermediate levels, and class III (AAV1 and 6) had the lowest levels. These expression levels were consistent across multiple cell lines.” (Earley, Abstract).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the AAV2 system disclosed by Earley to express the polypeptide encoded by the nucleic acid of Lu to arrive at the claimed invention because Earley discloses that AAV2 is a standard in this area of science.
A person of ordinary skill in the art would be motivated to use AAV2 vectors with AAV2 ITRs in order to perform gene delivery as disclosed by Earley.
A person of ordinary skill in the art would have a reasonable expectation of success because Earley discloses that these vectors with AAV2 ITRs have a high yield and are frequently used in this role.
Consequently, claim 32 is obvious over Lu et al. in view of Earley et al. and rejected.
Regarding claim 34, claim 32 is obvious as described above. The AAV vectors disclosed by Earley are AAV2 vectors and Lu discloses that the Ang-2 (angiopoietin) domain can be fused to the N-terminal of the VEGF binding domain:
“A chimeric molecule, which comprises an antibody and an Ang2 binding peptide, wherein said peptide is fused to the N-terminus or C-terminus of the light chains and/or heavy chains of said antibody, optionally with a peptide linker, wherein the peptide has an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity to a peptide selected from the group consisting of SEQ ID NOS:7-12, and wherein said antibody binds to VEGF.” (Lu et al., claim 17).
This claim amounts to placing a nucleic acid that encodes the polypeptide of Lu in the AAV2 cassette of Earley.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the AAV2 system disclosed by Earley to express the polypeptide encoded by the nucleic acid of Lu to arrive at the claimed invention because Earley discloses that AAV2 is a standard in this area of science.
A person of ordinary skill in the art would be motivated to use AAV2 vectors with AAV2 ITRs in order to perform gene delivery as disclosed by Earley.
A person of ordinary skill in the art would have a reasonable expectation of success because Earley discloses that these vectors with AAV2 ITRs have a high yield and are frequently used in this role.
Consequently, claim 34 is obvious over Lu et al. in view of Earley et al. and rejected.
Free of the Prior Art
Regarding claim 37, while not allowable, is free of the prior art for the following reasons. First, no valid prior art nucleic acids read on the sequences of claim 37. Furthermore, the closest reverse translation of Applicant SEQ ID NO: 7 is shown below aligned against the relevant region of SEQ ID NO: 14:
=======================================
#
# Aligned_sequences: 2
# 1:
# 2:
# Matrix: EDNAFULL
# Gap_penalty: 10.0
# Extend_penalty: 0.5
#
# Length: 1569
# Identity: 1164/1569 (74.2%)
# Similarity: 1164/1569 (74.2%)
# Gaps: 137/1569 ( 8.7%)
# Score: 4491.0
#
#
#=======================================
1 catggtgtcttattgggatactggcgtgctgctctgtgccctcctgagtt 50
||||||...||.|||||.||.|||||||||||.||.|||||.|||||.|
1 -atggtgagctactgggacaccggcgtgctgctgtgcgccctgctgagct 49
51 gcctgctcctgactggttcttcttctgggtc--cgatactgggcgcccct 98
|||||||.|||||.|| |..|..|.|.|.| |||.||.||..|.||||
50 gcctgctgctgaccgg--cagcagcagcggcagcgacaccggcagaccct 97
99 tcgtggagatgtactccgagatccctgaaatcattcacatgactgagggt 148
||||||||||||||..|||||||||.||.|||||.||||||||.|||||.
98 tcgtggagatgtacagcgagatccccgagatcatccacatgaccgagggc 147
149 cgggaactggtcatcccatgccgcgtgacctctcccaacattactgtgac 198
.|.||.|||||.|||||.|||.|.||||||...||||||||.||.|||||
148 agagagctggtgatcccctgcagagtgaccagccccaacatcaccgtgac 197
199 cctgaagaaattccctctggacaccctcatcccagatgggaagaggatca 248
|||||||||.|||||.|||||||||||.|||||.||.||.|||||.||||
198 cctgaagaagttccccctggacaccctgatccccgacggcaagagaatca 247
249 tttgggactcaagaaagggttttatcatcagcaacgctacatacaaggag 298
|.||||||...||||||||.||.||||||||||||||.||.|||||||||
248 tctgggacagcagaaagggcttcatcatcagcaacgccacctacaaggag 297
299 attggcctgctcacctgcgaagcaacagtgaacggacacctgtacaagac 348
||.||||||||.||||||||.||.||.||||||||.||||||||||||||
298 atcggcctgctgacctgcgaggccaccgtgaacggccacctgtacaagac 347
349 taattatctcacccatagacagacaaacactatcattgatgtggtcctgt 398
.||.||.||.|||||.||||||||.|||||.|||||.||.|||||.|||.
348 caactacctgacccacagacagaccaacaccatcatcgacgtggtgctga 397
399 caccaagccacggcatcgagctcagcgtcggtgaaaagctggtgctcaat 448
..||.|||||||||||||||||.|||||.||.||.|||||||||||.||.
398 gccccagccacggcatcgagctgagcgtgggcgagaagctggtgctgaac 447
449 tgtacagcccggactgagctgaacgtgggcattgacttcaattgggaata 498
||.||.|||.|.||.|||||||||||||||||.||||||||.|||||.||
448 tgcaccgccagaaccgagctgaacgtgggcatcgacttcaactgggagta 497
499 ccccagctccaagcaccagcataagaaactggtgaaccgcgatctcaaaa 548
|||||||..||||||||||||.|||||.|||||||||.|.||.||.||.|
498 ccccagcagcaagcaccagcacaagaagctggtgaacagagacctgaaga 547
549 cccagtccgg-atctgagatgaagaaatttctgagcaccctcacaatcga 597
|||||..||| |.| |||||||||||.||.|||||||||||.||.|||||
548 cccagagcggcagc-gagatgaagaagttcctgagcaccctgaccatcga 596
598 cggcgtgacacgatccgatcagggactgtatacttgcgccgcttctagtg 647
|||||||||..||..|||.|||||.|||||.||.||||||||....||.|
597 cggcgtgaccagaagcgaccagggcctgtacacctgcgccgccagcagcg 646
648 gcctgatgaccaagaaaaatagcacattcgtcagggtgcacgaaaaggac 697
||||||||||||||||.||.|||||.|||||.||.||||||||.||||||
647 gcctgatgaccaagaagaacagcaccttcgtgagagtgcacgagaaggac 696
698 aaaactcatacctgcccaccttgtccagcaccagagctgctcggaggacc 747
||.||.||.||||||||.||.||.||.||.||.||||||||.||.||.||
697 aagacccacacctgccccccctgccccgcccccgagctgctgggcggccc 746
748 atccgtgttcctgtttccacccaagcccaaagatactctgatgatttcac 797
...||||||||||||.||.|||||||||||.||.||.||||||| |||
747 cagcgtgttcctgttcccccccaagcccaaggacaccctgatga--tca- 793
798 gc---acacccgaagtcacttgcgtggtcgtggacgtgtcccacgaggac 844
|| ||.|||||.||.||.||||||||.|||||||||..||||||||||
794 gcagaacccccgaggtgacctgcgtggtggtggacgtgagccacgaggac 843
845 cccgaagtcaagtttaactggtacgtggacggcgtcgaggtgcataatgc 894
|||||.||.|||||.||||||||||||||||||||.||||||||.||.||
844 cccgaggtgaagttcaactggtacgtggacggcgtggaggtgcacaacgc 893
895 taagacaaaaccccgagaggaacagtacaactctacctatagggtcgtga 944
.|||||.||.|||.|||||||.|||||||||...|||||.||.||.||||
894 caagaccaagcccagagaggagcagtacaacagcacctacagagtggtga 943
945 gtgtcctgacagtgctccaccaggattggctgaacggaaaggagtataag 994
|.||.|||||.|||||.||||||||.|||||||||||.||||||||.|||
944 gcgtgctgaccgtgctgcaccaggactggctgaacggcaaggagtacaag 993
995 tgcaaagtgtctaataaggcactgcctgccccaatcgagaaaacaattag 1044
|||||.|||...||.|||||.|||||.|||||.||||||||.||.||.||
994 tgcaaggtgagcaacaaggccctgcccgcccccatcgagaagaccatcag 1043
1045 taaggccaaagggcagcccagagaacctcaggtgtacactctg-cctcca 1093
.||||||||.||.|||||||||||.||.|||||||||||.||| ||.|||
1044 caaggccaagggccagcccagagagccccaggtgtacaccctgcccccca 1093
1094 tctcgggacgagctcactaagaaccaggtcagtctgacctgtctcgtgaa 1143
.| .|.||||||||.||.|||||||||||.||.||||||||.||.|||||
1094 gc-agagacgagctgaccaagaaccaggtgagcctgacctgcctggtgaa 1142
1144 agggttctatcctagtgatatcgctgtggagtggga-atcaaatggtcag 1192
.||.|||||.||.||.||.|||||.||||||||||| |.| ||.||.|||
1143 gggcttctaccccagcgacatcgccgtggagtgggagagc-aacggccag 1191
1193 ccagagaacaattacaagaccacaccccctgtcctggacagcgatggctc 1242
||.||||||||.|||||||||||.|||||.||.|||||||||||.|||..
1192 cccgagaacaactacaagaccaccccccccgtgctggacagcgacggcag 1241
1243 cttctttctgtattccaagctcaccgtggacaa-atctcgatggcagcag 1291
||||||.|||||...||||||.||||||||||| |.| .|||||||||||
1242 cttcttcctgtacagcaagctgaccgtggacaagagc-agatggcagcag 1290
1292 ggaaacgtctttagttgttca--gtgatgcacgaagccctccataaccac 1339
||.|||||.||.||.|| || |||||||||||.|||||.||.||||||
1291 ggcaacgtgttcagctg--cagcgtgatgcacgaggccctgcacaaccac 1338
1340 tacactcagaaaagcctcagcctcagccctgggaa--------------- 1374
|||||.|||||.|||||.|||||.|||||.||.||
1339 tacacccagaagagcctgagcctgagccccggcaagggcggcggcggcgg 1388
1375 --------atgataa---------ggatatcaagatctacaaagcttat- 1406
|.||..| |||...|..||.||.| .|||..||
1389 cgcccagcaggaggagtgcgagtgggacccctggacctgc-gagcacatg 1437
1407 -----------cgataccgtcgactag----agc-tcgctgatcagcctc 1440
||..||||.||.| || ||| .||| ||||..|
1438 ggcagcggcagcgccaccggcggc-agcggcagcaccgc----cagcagc 1482
1441 gactgtgcct---------------------------------------- 1450
|.|.|.|.|.
1483 ggcagcggcagcgccacccaccaggaggagtgcgagtgggacccctggac 1532
1450 ------------------- 1450
1533 ctgcgagcacatgctggag 1551
This alignment does not meet the required 80% identity requirement and therefore the sequences of this claim cannot be made obvious with the available prior art and scientific knowledge.
Conclusion
No claim is allowed.
Claims 1-3, 6, 10, 13, 14, 18, 19, 25-27, 32, 34, 37, and 45 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to David Paul Bowles whose telephone number is (571)272-0919. The examiner can normally be reached Monday-Friday 8:30-5:00.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko Garyu can be reached on (571) 270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/DAVID PAUL BOWLES/ Examiner, Art Unit 1654
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654
Prosecution Insights