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 .
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) was submitted on 6/21/2023 and 3/27/2026, 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 1-4 and 6-15, filed 3/27/2026 are pending. Claims 1-4 and 6-15 are under examination.
Specification
The specification was previously objected to for usage of a trade name or a mark used in commerce.
Response to Arguments
Applicant’s arguments, see Applicant Reply, page 11, para. 2, filed 3/27/2026, with respect to objections to the specification have been fully considered and are persuasive. The objections to the specification have been withdrawn.
Claim Interpretation
Amended claim 1 recites: “A polypeptide consisting of i) an amino acid sequence as set forth in SEQ ID NO: 1, or ii) an amino acid sequence at least 80% identical to the amino acid sequence as set forth in SEQ ID NO:1. Claim 1 is interpreted such that the phrase “consisting of an amino acid sequence as set forth in SEQ ID NO: 1“ means that a sequence must match SEQ ID NO: 1 and be of the same length in order to read on claim 1 and the phrase “or an amino acid sequence at least 80% identical to the amino acid sequence as set forth in SEQ ID NO: 1” means that a sequence must have at least 80% identity with SEQ ID NO: 1 and does not have to match the length.
This is a consequence of the definition of “sequence identity” as given in para. [0032] of the specification:
“"Sequence identity" or "identity" in the context of two polypeptide sequences refers to the residues in the two sequences that are the same when aligned for maximum correspondence over a specified comparison window. When percentage of sequence identity is used in reference to proteins, it is recognized that residue positions which are not identical often differ by conservative amino acid substitutions, where amino acid residues are substituted for other amino acid residues with similar chemical properties (e.g., charge or hydrophobicity) and therefore do not change the functional properties of the molecule. When sequences differ in conservative substitutions, the percent sequence identity may be adjusted upwards to correct for the conservative nature of the substitution. Sequences that differ by such conservative substitutions are said to have "sequence similarity" or "similarity."
Means for making this adjustment are well known to those of skill in the art. Typically, this involves scoring a conservative substitution as a partial rather than a full mismatch, thereby increasing the percentage sequence identity. Thus, for example, where an identical amino acid is given a score of 1 and a non-conservative substitution is given a score of zero, a conservative substitution is given a score between zero and 1. The scoring of conservative substitutions is calculated, e.g., as implemented in the program PC/GENE (Intelligenetics, Mountain View, Calif).
"Percentage of sequence identity" includes the value determined by comparing two optimally aligned sequences over a comparison window, wherein the portion of the amino acid sequence in the comparison window may comprise additions or deletions (i.e., gaps) as compared to the reference sequence (which does not comprise additions or deletions) for optimal alignment of the two sequences.
The percentage is calculated by determining the number of positions at which the identical amino acid residue occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the window of comparison, and multiplying the result by 100 to yield the percentage of sequence identity.”
Consequently, any prior art sequence need only match the target polypeptide within the analysis window.
Claim Rejections - 35 USC § 112
Claims 8-15 were previously 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.
Response to Arguments
Applicant’s arguments, see Applicant Reply, page 12, para. 1, filed 3/27/2026,, with respect to claims 8-15 have been fully considered and are persuasive. The rejection of claims 8-15 has been withdrawn.
Claims 8-15 were rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Response to Arguments
Applicant’s arguments, see Applicant Reply, page 12, para. 3, filed 3/27/2026,, with respect to claims 8-15 have been fully considered and are persuasive. The rejection of claims 8-15 has been withdrawn.
Maintained 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.
Claim 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ghosh et al. (WO 03/087768, published 10/23/2003).
Ghosh et al. (WO 03/087768, published 10/23/2003) discloses SEQ ID NO: 195, aligned below:
Sequence 3002 AA;
Query Match 100.0%; Score 7272; Length 3002;
Best Local Similarity 100.0%;
Matches 1239; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DVNECLDPTTCISGNCVNTPGSYICDCPPDFELNPTRVGCVDTRSGNCYLDIRPRGDNGD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1618 DVNECLDPTTCISGNCVNTPGSYICDCPPDFELNPTRVGCVDTRSGNCYLDIRPRGDNGD 1677
Qy 61 TACSNEIGVGVSKASCCCSLGKAWGTPCEMCPAVNTSEYKILCPGGEGFRPNPITVILED 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1678 TACSNEIGVGVSKASCCCSLGKAWGTPCEMCPAVNTSEYKILCPGGEGFRPNPITVILED 1737
Qy 121 IDECQELPGLCQGGKCINTFGSFQCRCPTGYYLNEDTRVCDDVNECETPGICGPGTCYNT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1738 IDECQELPGLCQGGKCINTFGSFQCRCPTGYYLNEDTRVCDDVNECETPGICGPGTCYNT 1797
Qy 181 VGNYTCICPPDYMQVNGGNNCMDMRRSLCYRNYYADNQTCDGELLFNMTKKMCCCSYNIG 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1798 VGNYTCICPPDYMQVNGGNNCMDMRRSLCYRNYYADNQTCDGELLFNMTKKMCCCSYNIG 1857
Qy 241 RAWNKPCEQCPIPSTDEFATLCGSQRPGFVIDIYTGLPVDIDECREIPGVCENGVCINMV 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1858 RAWNKPCEQCPIPSTDEFATLCGSQRPGFVIDIYTGLPVDIDECREIPGVCENGVCINMV 1917
Qy 301 GSFRCECPVGFFYNDKLLVCEDIDECQNGPVCQRNAECINTAGSYRCDCKPGYRFTSTGQ 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1918 GSFRCECPVGFFYNDKLLVCEDIDECQNGPVCQRNAECINTAGSYRCDCKPGYRFTSTGQ 1977
Qy 361 CNDRNECQEIPNICSHGQCIDTVGSFYCLCHTGFKTNDDQTMCLDINECERDACGNGTCR 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1978 CNDRNECQEIPNICSHGQCIDTVGSFYCLCHTGFKTNDDQTMCLDINECERDACGNGTCR 2037
Qy 421 NTIGSFNCRCNHGFILSHNNDCIDVDECASGNGNLCRNGQCINTVGSFQCQCNEGYEVAP 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2038 NTIGSFNCRCNHGFILSHNNDCIDVDECASGNGNLCRNGQCINTVGSFQCQCNEGYEVAP 2097
Qy 481 DGRTCVDINECLLEPRKCAPGTCQNLDGSYRCICPPGYSLQNEKCEDIDECVEEPEICAL 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2098 DGRTCVDINECLLEPRKCAPGTCQNLDGSYRCICPPGYSLQNEKCEDIDECVEEPEICAL 2157
Qy 541 GTCSNTEGSFKCLCPEGFSLSSSGRRCQDLRMSYCYAKFEGGKCSSPKSRNHSKQECCCA 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2158 GTCSNTEGSFKCLCPEGFSLSSSGRRCQDLRMSYCYAKFEGGKCSSPKSRNHSKQECCCA 2217
Qy 601 LKGEGWGDPCELCPTEPDEAFRQICPYGSGIIVGPDDSAVDMDECKEPDVCKHGQCINTD 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2218 LKGEGWGDPCELCPTEPDEAFRQICPYGSGIIVGPDDSAVDMDECKEPDVCKHGQCINTD 2277
Qy 661 GSYRCECPFGYTLAGNECVDTDECSVGNPCGNGTCKNVIGGFECTCEEGFEPGPMMTCED 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2278 GSYRCECPFGYTLAGNECVDTDECSVGNPCGNGTCKNVIGGFECTCEEGFEPGPMMTCED 2337
Qy 721 INECAQNPLLCAFRCVNTYGSYECKCPVGYVLREDRRMCKDEDECEEGKHDCTEKQMECK 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2338 INECAQNPLLCAFRCVNTYGSYECKCPVGYVLREDRRMCKDEDECEEGKHDCTEKQMECK 2397
Qy 781 NLIGTYMCICGPGYQRRPDGEGCVDENECQTKPGICENGRCLNTRGSYTCECNDGFTASP 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2398 NLIGTYMCICGPGYQRRPDGEGCVDENECQTKPGICENGRCLNTRGSYTCECNDGFTASP 2457
Qy 841 NQDECLDNREGYCFTEVLQNMCQIGSSNRNPVTKSECCCDGGRGWGPHCEICPFQGTVAF 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2458 NQDECLDNREGYCFTEVLQNMCQIGSSNRNPVTKSECCCDGGRGWGPHCEICPFQGTVAF 2517
Qy 901 KKLCPHGRGFMTNGADIDECKVIHDVCRNGECVNDRGSYHCICKTGYTPDITGTSCVDLN 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2518 KKLCPHGRGFMTNGADIDECKVIHDVCRNGECVNDRGSYHCICKTGYTPDITGTSCVDLN 2577
Qy 961 ECNQAPKPCNFICKNTEGSYQCSCPKGYILQEDGRSCKDLDECATKQHNCQFLCVNTIGG 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2578 ECNQAPKPCNFICKNTEGSYQCSCPKGYILQEDGRSCKDLDECATKQHNCQFLCVNTIGG 2637
Qy 1021 FTCKCPPGFTQHHTSCIDNNECTSDINLCGSKGICQNTPGSFTCECQRGFSLDQTGSSCE 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2638 FTCKCPPGFTQHHTSCIDNNECTSDINLCGSKGICQNTPGSFTCECQRGFSLDQTGSSCE 2697
Qy 1081 DVDECEGNHRCQHGCQNIIGGYRCSCPQGYLQHYQWNQCVDENECLSAHICGGASCHNTL 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2698 DVDECEGNHRCQHGCQNIIGGYRCSCPQGYLQHYQWNQCVDENECLSAHICGGASCHNTL 2757
Qy 1141 GSYKCMCPAGFQYEQFSGGCQDINECGSAQAPCSYGCSNTEGGYLCGCPPGYFRIGQGHC 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2758 GSYKCMCPAGFQYEQFSGGCQDINECGSAQAPCSYGCSNTEGGYLCGCPPGYFRIGQGHC 2817
Qy 1201 VSGMGMGRGNPEPPVSGEMDDNSLSPEACYECKINGYPK 1239
|||||||||||||||||||||||||||||||||||||||
Db 2818 VSGMGMGRGNPEPPVSGEMDDNSLSPEACYECKINGYPK 2856
Regarding claim 1, because of the current claim interpretation of claim 1, claim 1 is anticipated by Ghosh and claim 1 is rejected.
Response to Arguments
Applicant's arguments filed 3/27/206 have been fully considered but they are not persuasive.
Applicant’s Reply, page 12, para. 7 asserts:
“As discussed during the interview, SEQ ID NO: 195 of Ghosh is the full length fibrillin sequence having 3002 amino acid residues. In contrast, SEQ ID NO: 1 of the present invention has 1239 amino acid residues. As discussed above, claim 1 is amended to clarify that the polypeptide consists of an amino acid sequence at least 80% identical to the amino acid sequence as set forth in SEQ ID NO: 1. While the length of such a polypeptide does not have to be exactly the same as SEQ ID NO: 1, it cannot be so different (larger or smaller) such that there is no longer at least 80% sequence identity. The sequence disclosed by Ghosh is significantly larger such that the entire polypeptide does not have at least 80% sequence identity to SEQ ID NO: 1.
Even though the full length fibrillin protein "comprises" a sequence that has 100% sequence identity to SEQ ID NO:1, the full length protein is 3002 amino acid residues and thus the protein does not "consist of" an amino acid sequence at least 80% identical to SEQ ID NO:1. Instead, the full length protein has an additional ~1500 amino acid residues which would be excluded by the closed "consisting of' language of claim 1. Thus, Ghosh does not anticipate claim 1.
Reconsideration and withdrawal of this rejection is thus respectfully requested.“
As discussed above in the claim interpretation section, the relevant identity is in the comparison window as defined by the specification. Consequently, the polypeptide of Ghosh “consists of” Applicant’s polypeptide with 100% identity.
Maintained 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.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Ghosh et al. (WO 03/087768, published 10/23/2003) in view of Biro et al. (Biro, et al. Biochemical and biophysical research communications 306.2: 408-415 (2003)).
Regarding claim 2, claim 1 is rejected as described above. Ghosh does not specifically disclose a nucleic acid encoding the polypeptide. However, Biro et al. discloses that: “The origin and development of the genetic code are not well understood. The 20 amino acids and the start and stop signals are coded redundantly by 64 codons. The amino acids (a.a.) may be classified according to basic physico-chemical properties, important ones being size, charge, and hydrophobicity. The four nucleic acids (n.a.) are either purines or pyrimidines and they form 64 different, simple patterns in the codons.” (Biro et al., page 408, col. 1, para. 1). Biro also discloses a copy of the codon to amino acid table. (Biro et al., page 410, Tables 1 and 2).
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 codon table disclosed by Biro to determine a nucleic acid sequence to encode for the protein disclosed by Ghosh. A person of ordinary skill in the art would do this in order to create an expression vector in order to express said protein. A person of ordinary skill in the would have a reasonable expectation of success because Biro describes how nucleic acid codons code for amino acids (Biro et al., page 410, Tables 1 and 2). Consequently, claim 2 is obvious over Ghosh and Biro and rejected.
Claims 3 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Ghosh et al. (WO 03/087768, published 10/23/2003) and Biro et al. (Biro, et al. Biochemical and biophysical research communications 306.2: 408-415 (2003) as applied to claim 2 above, and further in view of Hunt (Hunt, Ian. Protein expression and purification 40.1: 1-22 (2005)).
Regarding claim 3, claim 2 is rejected as described above. Ghosh and Biro do not explicitly disclose a vector. However, Hunt describes the usage of vectors for the expression of proteins of interest: “In most laboratories where protein preparation is performed, whether for small-scale protein production for exploratory research or in a drug discovery context for
target validation, large-scale expression (to facilitate high-throughput screening) or structural biology campaigns, the two main workhorses for the expression of recombinant proteins are undoubtedly Escherichia coli and baculovirus-mediated insect cell expression.” (Hunt, page 1, col. 1, para. 1). Hunt describes the preparation of vectors for this purpose: “Briefly, Gateway technology utilises a recombination process first observed in lambda phage to facilitate transfer of heterologous DNA sequences between two vectors. The reaction is catalysed by a mixture of enzymes that bind to specific signal sequences (called att sites) and covalently recombine the DNA into novel forms [3]. In Gateway, two recombination reactions constitute the basis of the cloning strategy.” (Hunt, page 3, col. 1, para. 2 and Hunt page 4, fig. 2)
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to put the nucleic acid of Ghosh and Biro into an expression vector system disclosed by Hunt and arrive at the claimed invention. A person of ordinary skill in the art would do this in order to create a system to express the protein encoded by the nucleic acid of Ghosh and Biro. A person of ordinary skill in the art would have a reasonable expectation of success because Hunt describes that this technology is routinely used in laboratories above (Hunt, page 1, col. 1, para. 1). Consequently, claim 3 is obvious over Ghosh and Biro as applied to claim 2, further in view of Hunt and rejected.
Regarding claim 4, claim 3 is rejected as described above. Hunt discloses the usage of a promoters to control protein expression in eukaryotic insect cells: “Several baculovirus expression systems are commercially available to drive recombinant protein expression. In the vast majority of instances, the gene of interest is cloned into a transfer vector which contains the sequences that flank the polyhedrin gene in the baculovirus genome. The viral genome and transfer vector are then co-transfected into the insect cell and the gene inserts into the virus genome via homologous recombination under the control of the strong late viral polyhedrin promoter ” (Hunt, page 10, col. 1, para. 3).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to put the nucleic acid of Ghosh and Biro into an expression vector system with a promoter for eukaryotic expression as disclosed by Hunt and arrive at the claimed invention. A person of ordinary skill in the art would do this in order to create a system to express the protein encoded by the nucleic acid of Ghosh and Biro in a eukaryotic system. A person of ordinary skill in the art would have a reasonable expectation of success because Hunt describes Hunt describes how these systems are commercially available and routinely used (Hunt, page 10, col. 1, para. 3). Consequently, claim 4 is obvious over Ghosh et al. and Biro et al. as applied to claim 2, further in view of Hunt and rejected.
Claims 6 is rejected under 35 U.S.C. 103 as being unpatentable over Ghosh et al. (WO 03/087768, published 10/23/2003) in view of Chaudhari et al., (Chaudhari, et al. Int J Adv Pharm Biol Chem 1.1: 21-34 (2012)).
Regarding claim 6, claim 1 is rejected as described above. Ghosh does not disclose a pharmaceutically acceptable carrier. However, Chaudhari discloses that: “Many dosage forms formulated today are complex system containing many other components along with the active pharmaceutical ingredient (API); these compounds are generally added along with the active pharmaceutical ingredients…” (Chaudhari, page 21, col. 1, para. 1). Chaudhari also discloses numerous pharmaceutical carriers and excipients in Table 1 and reasons for using said carriers and excipients. (Chaudhari et al., page 28, Table 1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the polypeptide of Ghosh with the pharmaceutical carriers and excipients of Chaudhari and arrive at the claimed invention. A person of ordinary skill in the art would do this in order to gain the benefits described in Chaudhari such as enhanced stability and improved bioavailability (Chaudhari et al., page 21, col. 1, para. 1). A person would have a reasonable expectation of success because Chaudhari describes their importance to drug products in general (Chaudhari, et al. page 21, Abstract). Consequently, claim 6 is obvious over Ghosh et al. in view of Chaudhari et al. and rejected.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Ghosh et al. (WO 03/087768, published 10/23/2003) and Chaudhari et al., (Chaudhari, et al. Int J Adv Pharm Biol Chem 1.1: 21-34 (2012) as applied to claim 6 above, and further in view of Laurent (Laurent, Stéphane. Pharmacological research 124: 116-125 (2017)).
Regarding claim 7, Ghosh and Chaudhari do not explicitly disclose the usage of an antihypertensive agent. However, Laurent discloses the usage of antihypertensive agents wherein some agents have vasodilating activity and some do lack this activity (Laurent, page 118, Table 1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the polypeptide of Ghosh and Chaudhari with the antihypertensive agent of Laurent. A person of ordinary skill in the art would do this in order to gain the benefits described in Laurent of said antihypertensive agent (Laurent, page 118, Table 1). A person of ordinary skill in the art would have a reasonable expectation of success because Laurent describes how these drugs are used in a complementary manner: “In conclusion, the various mechanisms of action of the pharmacological classes of antihypertensive drugs described in this review show their complementarity for treating hypertension, well known as a mosaic of pathophysiological disturbances.” (Laurent, page 123, col. 2, para. 7). Consequently, claim 7 is obvious over Ghosh et al. and Chaudhari et al. as applied to claim 6 above, further in view of Laurent and rejected.
Response to Arguments
Applicant's arguments filed 3/27/2026 have been fully considered but they are not persuasive.
Applicant’s Reply, page 13, para. 5 asserts:
“Claim 2 was rejected as being unpatentable over Ghosh et al. (WO 03/087768) in view of Biro et al. (Biochemical and biophysical research communications, 2003). This rejection is traversed.
As discussed above, Ghosh does not anticipate the claimed invention. Ghosh also does not make the claimed invention obvious as Ghosh does not teach or suggest the specific fibrillin fragment which has pro-angiogenic and vessel normalization properties. Biro does not compensate for the deficiencies of Ghosh as this reference was only relied upon for teaching how to determine a nucleic acid sequence.
Therefore, the claimed invention is not obvious over any combination of the cited references. Reconsideration and withdrawal of this rejection is thus respectfully requested.
Claims 3 and 4 were rejected as being unpatentable over Ghosh et al. (WO 03/087768) in view of Biro et al. (Biochemical and biophysical research communications, 2003), further in view of Hunt (Protein expression and purification, 2005). This rejection is traversed.
As discussed above, Ghosh and Biro would not make the claimed invention obvious as neither reference teaches or suggests the specific fibrillin fragment which has pro-angiogenic and vessel normalization properties. Hunt does not compensate for the deficiencies of Ghosh and Biro as this reference was only relied upon for teaching the use of vectors.
Therefore, the claimed invention is not obvious over any combination of the cited references. Reconsideration and withdrawal of this rejection is thus respectfully requested.
Claim 6 was rejected as being unpatentable over Ghosh et al. (WO 03/087768) in view of Chaudhari et al. (Int JAdv Pharm Biol Chem, 2012). This rejection is traversed.
As discussed above, Ghosh does not make the claimed invention obvious as Ghosh does not teach or suggest the specific fibrillin fragment which has pro-angiogenic and vessel normalization properties. Chaudhari does not compensate for the deficiencies of Ghosh as this reference was only relied upon for teaching pharmaceutically acceptable carriers.
Therefore, the claimed invention is not obvious over any combination of the cited references. Reconsideration and withdrawal of this rejection is thus respectfully requested.
Claim 7 was rejected as being unpatentable over Ghosh et al. (WO 03/087768) in view of Chaudhari et al. (Int J Adv Pharm Biol Chem, 2012) and Laurent (Pharmacological research, 2017). This rejection is traversed.
As discussed above, Ghosh and Chaudhari do not make the claimed invention obvious as these references do not teach or suggest the specific fibrillin fragment which has pro-angiogenic and vessel normalization properties. Laurent does not compensate for the deficiencies of Ghosh and Chaudhari as this reference was only relied upon for teaching an antihypertensive agent.
Therefore, the claimed invention is not obvious over any combination of the cited references. Reconsideration and withdrawal of this rejection is thus respectfully requested.
As described above, Ghosh anticipates the second clause “ii)” of claim 1. Consequently there are no deficiencies to remedy as far as the sequence for the art supplied in these rejections. No other arguments are offered as to why these references do not render these claims rejected.
New Rejection - Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 2, 6, and 7 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because the claimed invention is directed to a product of nature without significantly more. The claim(s) recite(s) SEQ ID NO: 1, which matches a fragment of a naturally occurring protein.
Regarding claim 1, claim 1 recites: “A polypeptide consisting of i) an amino acid sequence as set forth in SEQ ID NO: 1, or ii) an amino acid sequence at least 80% identical to the amino acid sequence as set forth in SEQ ID NO:1.”
Ghosh et al. (WO 03/087768, published 10/23/2003) discloses SEQ ID NO: 195, aligned below:
Sequence 3002 AA;
Query Match 100.0%; Score 7272; Length 3002;
Best Local Similarity 100.0%;
Matches 1239; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DVNECLDPTTCISGNCVNTPGSYICDCPPDFELNPTRVGCVDTRSGNCYLDIRPRGDNGD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1618 DVNECLDPTTCISGNCVNTPGSYICDCPPDFELNPTRVGCVDTRSGNCYLDIRPRGDNGD 1677
Qy 61 TACSNEIGVGVSKASCCCSLGKAWGTPCEMCPAVNTSEYKILCPGGEGFRPNPITVILED 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1678 TACSNEIGVGVSKASCCCSLGKAWGTPCEMCPAVNTSEYKILCPGGEGFRPNPITVILED 1737
Qy 121 IDECQELPGLCQGGKCINTFGSFQCRCPTGYYLNEDTRVCDDVNECETPGICGPGTCYNT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1738 IDECQELPGLCQGGKCINTFGSFQCRCPTGYYLNEDTRVCDDVNECETPGICGPGTCYNT 1797
Qy 181 VGNYTCICPPDYMQVNGGNNCMDMRRSLCYRNYYADNQTCDGELLFNMTKKMCCCSYNIG 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1798 VGNYTCICPPDYMQVNGGNNCMDMRRSLCYRNYYADNQTCDGELLFNMTKKMCCCSYNIG 1857
Qy 241 RAWNKPCEQCPIPSTDEFATLCGSQRPGFVIDIYTGLPVDIDECREIPGVCENGVCINMV 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1858 RAWNKPCEQCPIPSTDEFATLCGSQRPGFVIDIYTGLPVDIDECREIPGVCENGVCINMV 1917
Qy 301 GSFRCECPVGFFYNDKLLVCEDIDECQNGPVCQRNAECINTAGSYRCDCKPGYRFTSTGQ 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1918 GSFRCECPVGFFYNDKLLVCEDIDECQNGPVCQRNAECINTAGSYRCDCKPGYRFTSTGQ 1977
Qy 361 CNDRNECQEIPNICSHGQCIDTVGSFYCLCHTGFKTNDDQTMCLDINECERDACGNGTCR 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1978 CNDRNECQEIPNICSHGQCIDTVGSFYCLCHTGFKTNDDQTMCLDINECERDACGNGTCR 2037
Qy 421 NTIGSFNCRCNHGFILSHNNDCIDVDECASGNGNLCRNGQCINTVGSFQCQCNEGYEVAP 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2038 NTIGSFNCRCNHGFILSHNNDCIDVDECASGNGNLCRNGQCINTVGSFQCQCNEGYEVAP 2097
Qy 481 DGRTCVDINECLLEPRKCAPGTCQNLDGSYRCICPPGYSLQNEKCEDIDECVEEPEICAL 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2098 DGRTCVDINECLLEPRKCAPGTCQNLDGSYRCICPPGYSLQNEKCEDIDECVEEPEICAL 2157
Qy 541 GTCSNTEGSFKCLCPEGFSLSSSGRRCQDLRMSYCYAKFEGGKCSSPKSRNHSKQECCCA 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2158 GTCSNTEGSFKCLCPEGFSLSSSGRRCQDLRMSYCYAKFEGGKCSSPKSRNHSKQECCCA 2217
Qy 601 LKGEGWGDPCELCPTEPDEAFRQICPYGSGIIVGPDDSAVDMDECKEPDVCKHGQCINTD 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2218 LKGEGWGDPCELCPTEPDEAFRQICPYGSGIIVGPDDSAVDMDECKEPDVCKHGQCINTD 2277
Qy 661 GSYRCECPFGYTLAGNECVDTDECSVGNPCGNGTCKNVIGGFECTCEEGFEPGPMMTCED 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2278 GSYRCECPFGYTLAGNECVDTDECSVGNPCGNGTCKNVIGGFECTCEEGFEPGPMMTCED 2337
Qy 721 INECAQNPLLCAFRCVNTYGSYECKCPVGYVLREDRRMCKDEDECEEGKHDCTEKQMECK 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2338 INECAQNPLLCAFRCVNTYGSYECKCPVGYVLREDRRMCKDEDECEEGKHDCTEKQMECK 2397
Qy 781 NLIGTYMCICGPGYQRRPDGEGCVDENECQTKPGICENGRCLNTRGSYTCECNDGFTASP 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2398 NLIGTYMCICGPGYQRRPDGEGCVDENECQTKPGICENGRCLNTRGSYTCECNDGFTASP 2457
Qy 841 NQDECLDNREGYCFTEVLQNMCQIGSSNRNPVTKSECCCDGGRGWGPHCEICPFQGTVAF 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2458 NQDECLDNREGYCFTEVLQNMCQIGSSNRNPVTKSECCCDGGRGWGPHCEICPFQGTVAF 2517
Qy 901 KKLCPHGRGFMTNGADIDECKVIHDVCRNGECVNDRGSYHCICKTGYTPDITGTSCVDLN 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2518 KKLCPHGRGFMTNGADIDECKVIHDVCRNGECVNDRGSYHCICKTGYTPDITGTSCVDLN 2577
Qy 961 ECNQAPKPCNFICKNTEGSYQCSCPKGYILQEDGRSCKDLDECATKQHNCQFLCVNTIGG 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2578 ECNQAPKPCNFICKNTEGSYQCSCPKGYILQEDGRSCKDLDECATKQHNCQFLCVNTIGG 2637
Qy 1021 FTCKCPPGFTQHHTSCIDNNECTSDINLCGSKGICQNTPGSFTCECQRGFSLDQTGSSCE 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2638 FTCKCPPGFTQHHTSCIDNNECTSDINLCGSKGICQNTPGSFTCECQRGFSLDQTGSSCE 2697
Qy 1081 DVDECEGNHRCQHGCQNIIGGYRCSCPQGYLQHYQWNQCVDENECLSAHICGGASCHNTL 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2698 DVDECEGNHRCQHGCQNIIGGYRCSCPQGYLQHYQWNQCVDENECLSAHICGGASCHNTL 2757
Qy 1141 GSYKCMCPAGFQYEQFSGGCQDINECGSAQAPCSYGCSNTEGGYLCGCPPGYFRIGQGHC 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2758 GSYKCMCPAGFQYEQFSGGCQDINECGSAQAPCSYGCSNTEGGYLCGCPPGYFRIGQGHC 2817
Qy 1201 VSGMGMGRGNPEPPVSGEMDDNSLSPEACYECKINGYPK 1239
|||||||||||||||||||||||||||||||||||||||
Db 2818 VSGMGMGRGNPEPPVSGEMDDNSLSPEACYECKINGYPK 2856
Ghosh discloses that this is a polypeptide from human heart mitochondria: “Mitochondrial targets for drug screening assays and for therapeutic intervention in the treatment of diseases associated with altered mitochondrial function are provided. Complete amino acid sequences [SEQ ID NOS:1-3025] of polypeptides that comprise the human heart mitochondrial proteome are provided, using fractionated proteins derived from highly purified mitochondrial preparations, to identify previously unrecognized mitochondrial molecular components.” (Ghosh et al., Abstract).
As described by the claim interpretation and 102 rejection section above, this polypeptide reads on Applicant claim 1.
Step 2A, prong two:
This judicial exception is not markedly different from the nature-based product as shown above in the sequence alignment.
Step 2B:
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claim is directed to only a polypeptide.
Consequently, claim 1 is rejected.
Regarding claim 2, claim 2 recites: “A nucleic acid molecule encoding the polypeptide as defined in claim 1.”
Such a nucleic acid would necessarily need to exist within human mitochondria for the polypeptide from claim 1 to exist.
Step 2A, prong two:
This judicial exception is not markedly different from the nature-based product as shown above in the sequence alignment.
Step 2B:
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claim is directed to only a nucleic acid.
Consequently, claim 2 is rejected.
Regarding claim 6, claim 1 is rejected as described above. Claim 6 recites: “A pharmaceutical composition comprising an effective amount of one or more polypeptides according to claim 1 and at least one pharmaceutically acceptable carrier and/or vehicle.”
The polypeptide of claim 1 is a natural product as described above. The issue in question with claim 6 is the presence of a pharmaceutically acceptable carrier.
Step 2A, prong two:
This judicial exception is not markedly different from the nature-based product as shown above in the sequence alignment.
Step 2B:
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception.
MPEP 2106.05(d) states: “If the additional element (or combination of elements) is a specific limitation other than what is well-understood, routine and conventional in the field, for instance because it is an unconventional step that confines the claim to a particular useful application of the judicial exception, then this consideration favors eligibility. If, however, the additional element (or combination of elements) is no more than well-understood, routine, conventional activities previously known to the industry, which is recited at a high level of generality, then this consideration does not favor eligibility.”
In this case, the additional element is a pharmaceutically acceptable carrier.
Chaudhari et al. (Chaudhari, et al. "Pharmaceutical excipients: a review." Int J Adv Pharm Biol Chem 1.1: 21-34 (2012)) discloses that this is a well-understood and routine addition: “Excipients play an important role in formulating a dosage form. These are the ingredients which along with active pharmaceutical ingredients make up the dosage forms. Excipients act as protective agents, bulking agents and can also be used to improve bioavailability of drugs in some instances, the following review discusses the various types and sources of excipients along with their uses, and these can be used for different activities. Specific excipients are best suited for a particular dosage form; the select ion criterion for excipients and various interact ions that an excipient can undergo during its course of stay in formulation has been discussed in this review. Some excipient interact ions can be detrimental and need to be avoided. This has been detailed out in the interact ion sect ion. Excipients as like other active pharmaceutical ingredients need to be stabilized and standardized; the following review gives brief information about standardization and stabilization process along with the safety evaluation parameters of the excipients.” (Chaudhari et al., Abstract).
Consequently, claim 6 is rejected.
Regarding claim 7, claim 6 is rejected as described above. Claim 7 recites: “The pharmaceutical composition of claim 6, further comprising an anticoagulant, an anti-thrombotic agent, an anti-platelet agent, a fibrinolytic agent, a hypolipidemic agent, an antihypertensive agent, and/or an anti-ischemic agent.”
Step 2A, prong two:
This judicial exception is not markedly different from the nature-based product as shown above in the sequence alignment.
Step 2B:
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception.
MPEP 2106.05(d) states: “If the additional element (or combination of elements) is a specific limitation other than what is well-understood, routine and conventional in the field, for instance because it is an unconventional step that confines the claim to a particular useful application of the judicial exception, then this consideration favors eligibility. If, however, the additional element (or combination of elements) is no more than well-understood, routine, conventional activities previously known to the industry, which is recited at a high level of generality, then this consideration does not favor eligibility.”
In this case, the additional element is an anticoagulant, an anti-thrombotic agent, an anti-platelet agent, a fibrinolytic agent, a hypolipidemic agent, an antihypertensive agent, and/or an anti-ischemic agent.”
Laurent et al. (Laurent, Stéphane. Pharmacological research 124: 116-125 (2017)) discloses that usage of an antihypertensive agent is routine and well-understood: ““In conclusion, the various mechanisms of action of the pharmacological classes of antihypertensive drugs described in this review show their complementarity for treating hypertension, well known as a mosaic of pathophysiological disturbances.” (Laurent, page 123, col. 2, para. 7).
Claim 7 is rejected.
New Rejection- Claim Rejections - 35 USC § 112
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 8-15 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating retinal vasculature with human fragment 1487-2725, does not reasonably provide enablement for treating any possible ischemic disorder or vascular disease with a polypeptide comprising the amino acid sequence as set forth in SEQ ID NO: 1. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a), the Federal Circuit developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any necessary experimentation required by the specification is "reasonable" or is "undue." Consistent with Amgen Inc. et al. v. Sanofi et al., 598 U.S. 594, 2023 USPQ2d 602 (2023), the Wands factors continue to provide a framework for assessing enablement in a utility application or patent, regardless of technology area. Guidelines for Assessing Enablement in Utility Applications and Patents in View of the Supreme Court Decision in Amgen Inc. et al. v. Sanofi et al., 89 FR 1563 (January 10, 2024). These factors include, but are not limited to:
The breadth of the claims;
Amended claim 8 recites: “A method of treating ischemia or ischemic diseases or vascular diseases in a subject in need thereof, comprising administering to the subject an effective amount of one or more polypeptides comprising the amino acid sequence as set forth in SEQ ID NO: 1.”
This is broad in two ways. First the genus of any possible ischemic disease or vascular disease is very broad. Second, the polypeptide comprising SEQ ID NO: 1 is open-ended and is a potentially size-unlimited genus.
The nature of the invention;
The invention is a method of treating vascular diseases or ischemic diseases with a fragment of human fibrillin-1.
The state of the prior art;
Mariko et al. (Mariko, et al. American Journal of Physiology-Cell Physiology 299.5: C977-C987 (2010)) discloses that different fragments of fibrillin-1 possess different properties when introduced as a therapeutic:
“Here, we have shown that aortic microfibrils induced a substantial dose-dependent elevation of cytoplasmic and nuclear free calcium levels in endothelial cells. In particular, the rise in nuclear calcium level is known to modulate the activity of transcription factors and stimulate gene expression and cell proliferation (57) and may explain, at least in part, the increased cell proliferation triggered by microfibrils. To know which component of microfibrils was responsible for this effect, we studied the action of two RGD-containing overlapping fragments of their main component fibrillin-1, i.e., fragments PF9 and PF14. Although PF14 contains a wider sequence than PF9 on the NH2-terminal side of the RGD, both fragments promote in vitro adhesion of fibroblasts (5, 6) and, according to the present experiments and previous results (70), endothelial cells. However, only PF14, not PF9, induced a substantial dose-dependent [Ca2+]i increase in HUVECs, although lower than the rise induced by aortic microfibrils. The different responses induced by PF9 and PF14 confirm the importance of the amino acids on the NH2-terminal side of the RGD sequence of PF14 for cell recognition and/or function, as suggested previously (6, 40).” (Mariko et al., page C984, col. 2, para. 3).
Zeyer et al. (Zeyer, et al. Mutation Research/Reviews in Mutation Research 765: 7-18 (2015)) discloses a large number of mutations that occur before position 1487 in Table 2, excerpt below:
PNG
media_image1.png
962
587
media_image1.png
Greyscale
(Zeyer et al., page 12, Table 2).
There is some suggestion of fibrillin-1 as a future therapy for altering arterial wall phenotype by Mariko et al. 2 (Mariko, et al. The Journal of pathology 224.1: 33-44.) (2011):
“The above findings clearly indicate that fibrillin-1 is an important structural and instructive determinant of arterial wall morphogenesis, mechanical compliance, and tissue homeostasis. It is conceivable to argue that some of these functions are accounted for by the role of microfibrils in regulating cell performance through the interaction of fibrillin-1 with cell surface receptors, such as integrins and heparan sulphate proteoglycans, and latent TGFβ complexes. For example, fibrillin-1 triggers integrin-mediated signalling, which may regulate the adhesion and spreading of vascular smooth muscle cells (VSMCs) that could be required for the proper organization of aortic tissue during development 43, 44. Furthermore, improper activation of TGF signalling, as a result of impaired sequestration of latent complexes in the extracellular matrix, could also promote changes in VSMC phenotype. Moreover, it has recently been shown that fibrillin-1 fragments and microfibrils, which can pass through the basement membrane and anchor the endothelial cells to the internal elastic lamina 45, trigger integrin-mediated calcium signalling in endothelial cells 46, whose dysfunction has clearly been involved in the pathogenesis of Marfan syndrome 41, 47.” (Mariko et al. 2, page 42, col. 1, para. 5).
(D) The level of one of ordinary skill;
A person of ordinary skill in the art in the field of protein therapeutic design is usually at least a Master’s level education.
(E) The level of predictability in the art;
Protein-protein interactions are generally unpredictable. 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 et al., page 262, Table 2). The scope of the claims currently may incorporate such motifs and result in non-functional aggregates.
(F) The amount of direction provided by the inventor and the existence of working examples and the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Applicant provides one main example: human fragment 1487-2725.
Regarding claim 8, claim 8 recites: “A method of treating ischemia or ischemic diseases or vascular diseases in a subject in need thereof, comprising administering to the subject an effective amount of one or more polypeptides comprising the amino acid sequence as set forth in SEQ ID NO: 1.
Addressing the treating of any possible ischemia, ischemic diseases, or vascular diseases, Mariko discloses that various fragments of fibrillin-1 have different properties and therapeutic potential. Mariko 2 discloses the usage of fibrillin-1 in only general terms. The prior art does not disclose specific details of how fibrillin-1 or fibrillin-1 fragments interact with specific disease states.
Addressing the breadth of the claimed protein sequence, many of the claimed proteins will incorporate deleterious residues as disclosed by Zeyer. Furthermore, it is unpredictable as to what the effects of additional residues not enumerated by Zeyer will be to the function of the disclosed human fragment 1487-2725.
It would require undue experimentation to test all the claimed the protein sequences against all the claimed disease states to ensure efficacy for the method.
Claim 8 is rejected.
Regarding claim 9, claim 8 is rejected as described above. Claim 9 further recites the method of claim 8, wherein said ischemic diseases are peripheral ischemic diseases, ischemic heart diseases, retinopathies, age-related macular degeneration (AMD), hemangiomas, varicose veins, aneurysms and cerebrovascular diseases/malformations, or inflammation or diabetes-induced vascular disease.
This genus of diseases is smaller than the genus of claim 8, but these diseases would still require undue experimentation to test against the broad genus of claimed sequences.
Claim 9 is rejected.
Regarding claim 10, claim 9 is rejected as described above. Claim 10 further recites the method of claim 9, wherein said peripheral ischemic diseases are peripheral arterial diseases, peripheral occlusive arterial disease, lower limb artery ischemic diseases, distal limb ischemic diseases, thromboembolic disorders, venous thrombosis, deep vein thrombosis, thrombophlebitis, arterial embolism, or wound healing.
This genus of diseases is smaller than the genus of claim 9, but these diseases would still require undue experimentation to test against the broad genus of claimed sequences.
Claim 10 is rejected.
Regarding claim 11, claim 9 is rejected as described above. Claim 11 further recites the method of claim 9, wherein said ischemic heart diseases are cardiovascular diseases coronary arterial disease, coronary arterial thrombosis, myocardial infarction, angina pectoris, acute coronary syndrome, atrial fibrillation, ischemic sudden death, or transient ischemic attack.
This genus of diseases is smaller than the genus of claim 9, but these diseases would still require undue experimentation to test against the broad genus of claimed sequences.
Claim 11 is rejected.
Regarding claim 12, claim 8 is rejected as described above. Claim 12 further recites the method of claim 8, wherein said ischemic diseases are diabetic retinopathy, ocular ischemia, ischemic cerebrovascular diseases, cerebral arterial thrombosis, cerebral embolism, kidney embolism, pulmonary embolism, and ischemia and/or thrombosis resulting from (a) prosthetic valves or other implants, (b) indwelling catheters, (c) stents, (d) cardiopulmonary bypass, (e) hemodialysis, or (f) other procedures in which blood is exposed to an artificial surface that promotes thrombosis.
This genus of diseases is smaller than the genus of claim 8, but these diseases would still require undue experimentation to test against the broad genus of claimed sequences.
Claim 12 is rejected.
Regarding claim 13-15, these are ultimately dependent upon claim 8 and they do not reduce the genus size of proteins or diseases and therefore are also rejected.
Claims 13-15 are rejected.
Conclusion
No claim is allowed.
Claims 1-4 and 6-15 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.
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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.
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/DAVID PAUL BOWLES/ Examiner, Art Unit 1654
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654
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