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 .
Claims 1-20 are pending and examined on the merits.
Election/Restrictions
Applicant’s election of Group I (claims 1-19) in the reply filed on 8/14/2026 is acknowledged. Because Applicant did not distinctly and specifically point out any errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Applicant’s election of the following species in the reply filed on 8/14/2026 is acknowledged. Because Applicant did not distinctly and specifically point out any errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
A. Claim 1: SEQ ID NO: 92.
B. Claim 2: substitution positions 105/256/433/453/853.
C. Claim 3: substitution positions 75/437.
D. Claim 4: substitution positions 178/618.
E. Claim 5: substitution position 885.
F. Claim 6: substitution positions 79/329.
G. Claim 7: substitution position 75.
H. Claim 8: substitution positions 79/437/458
I. Claim 9: substitution positions 66/111 /114/181/185/374/603/604/897.
J. Claim 10: substitution positions 66/97/180/437/613.
K. Claim 11: substitution positions 66/111.
L. Claim 12: substitution positions 66/111 /601 /604/623/726/853.
M. Claim 13: engineered cytochrome P450-BM3 variants set forth in Table 13.1.
N. Claim 13: SEQ ID NO: 680.
Based on the election of SEQ ID NO:92 or SEQ ID NO:680 by the applicant, all claims that are drawn to or read on SEQ IDNO:92 and any of the elected amino acid positions that read on SEQ ID NO:92 are now under consideration. To that extent claims 1, 3, 13-19 which read on SEQ ID NO:92 or SEQ ID NO:680 are now under examination.
Claims 2, 4-12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 8/14/2026.
Claims 1-19 are pending.
Claim 2, 4-12, 20 stands withdrawn pursuant to 37 CFR 1.142(b).
Claims 1, 3, 13-19 are pending and examined on the merits.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 9/18/2024 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
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 1, 3, 13-19 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. Claims are examined to the extent that they read on elected species SEQ ID NO: 92.
MPEP 2163.II.A.2.(a).i) states, “Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention”.
For claims drawn to a genus, MPEP § 2163 states 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 applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
Claims 1, 3, 13-19 are drawn to an engineered cytochrome P450-BM3 variant comprising a polypeptide sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more sequence identity to SEQ ID NO: 92 or SEQ IDNO:680 or a functional fragment thereof, wherein the polypeptide sequence of said engineered cytochrome P450-BM3 variant comprises at least one substitution or substitution set and wherein the amino acid positions of said polypeptide sequence are numbered with reference to SEQ ID NO: 92. The structure and function of an engineered cytochrome P450-BM3 variant’s functional fragment thereof is a large number of sequences as a ‘functional fragment thereof’ (a fragment) only needs to be comprised of 2 contiguous bases. It is recommended that Applicant amend the claim to add a functional limitation.
In this case, the specification discloses the following representative species of an engineered cytochrome P450-BM3 variant are encompassed by the claims (i.e. an engineered cytochrome P450-BM3 variant comprising a polypeptide sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% to SEQ ID NO: 92 (claim 1)). Other than the above disclosed species, there is no prior-art or disclosed teaching as to the large number of engineered cytochrome P450-BM3 variants “functional fragment” thereof. The breadth of the claims encompass a large number of sub-sequences of engineered cytochrome P450-BM3 comprising SEQ ID NO:92
An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004). Here, the disclosure fails to teach which combinations of amino acids out of the numerous possibilities encompass a functional fragment thereof for the production of an engineered cytochrome P450-BM3 variant.
Accordingly, one of skill in the art would not accept the disclosure of SEQ ID NO: 92 as being representative of all engineered cytochrome P450-BM3 variant “functional fragment” thereof as encompassed by the claims. As such, the specification, taken with the pre-existing knowledge in the art of engineered cytochrome P450-BM3 variants, fails to satisfy the written description requirement of 35 U.S.C. 112, first paragraph.
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 13, 15 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claims 13, 15 are rejected as they read on the elected species SEQ ID NO: 92
Claim 13 attempts to incorporate by reference the engineered cytochrome P450-BM3 variants recited in various Tables including Table 13.1 of the specification. However, as clearly noted in M.P.E.P. 2173.05(s), this kind of reference to table or figures is only permitted when there is no way to clearly describe the content of the table or figure in words within the claim. It is not, however, permitted merely for Applicant’s convenience.
The 20 different engineered cytochrome P450-BM3 variants of Table 13.1 and their SEQ ID NOs can be listed in the claim in order to overcome the instant rejection.
Regarding claim 15, the phrase "improved activity on a substrate", in line 3, renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. It is unclear if the claim encompasses the claimed polypeptide in claims 1, 14. It is suggested that Applicant amend the claim to include comparison claim limitations. Appropriate correction is suggested.
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.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 13-19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Osbourne et al (US 2017/0247667 A1, Date Published: Aug. 31, 2017, cited on IDS dated 9/18/2024) {herein Osbourne ‘667}. Claims 1, 13-19 are rejected as they read on the elected species SEQ ID NO: 92.
Claims 1, 13-19 are drawn to an engineered cytochrome P450-BM3 variant comprising a polypeptide sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more sequence identity to SEQ ID NO: 92, or SEQ ID NO:680or a functional fragment thereof, wherein the polypeptide sequence of said engineered cytochrome P450-BM3 variant comprises at least one substitution or substitution set and wherein the amino acid positions of said polypeptide sequence are numbered with reference to SEQ ID NO: 92.
With respect to claims 1, 13-19, Osbourne ‘667 teaches a composition comprising P450-BM3 variant with at least one substitution that exhibits improved activity over a wide range of substrates (abstract, para 0004, appendix A). Said variant is 99% identical to the instant application SEQ ID NO: 92 (appendix A). —Furthermore, Osbourne ‘667 provides expression vectors comprising at least one polynucleotide sequence (para 0007). Said polynucleotide sequence is operably linked with at least one regulatory sequence suitable for expression of the polynucleotide sequence in a suitable host cell (para 0007).
For the reasons stated herein, the teachings of Osbourne ‘667 anticipates claims 1, 13-19.
Claims 1, 3, 13-19 are rejected under 35 U.S.C. 102a1 as being anticipated by Arnold et al (US Patent No. US7,524,664 B2, Date of Patent: Apr. 28, 2009). Claims 1, 3, 13-19 are rejected as they read on the elected species SEQ ID NO: 92 or SEQ ID NO:680
Claims 1, 3, 13-19 are drawn to an engineered cytochrome P450-BM3 variant comprising a polypeptide sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more sequence identity to SEQ ID NO: 92 or SEQ ID NO:680, or a functional fragment thereof, wherein the polypeptide sequence of said engineered cytochrome P450-BM3 variant comprises at least one substitution or substitution set and wherein the amino acid positions of said polypeptide sequence are numbered with reference to SEQ ID NO: 92.
With respect to claims 1, 3, 13-19, Arnold teaches cytochrome P45O BM-3 from Bacillus megaterium was engineered using a combination of directed evolution and site directed mutagenesis to hydroxylate linear alkanes regio- and enantio selectively using atmospheric dioxygen as an oxidant (abstract). The polynucleotide of the P450 mutant was screened (column 12, lines 30-35). Said sequence may be optimized in which the specific region optimized is replaced with a synthetically mutagenized oligonucleotide (column 12, lines 51-56). Said mutant was cloned into a parent strain for protein synthesis (column 12, lines 30-41). Said engineered P450 is 97.7% identical to the instant application SEQ ID NO: 92 (appendix B). Furthermore, said P450 mutant has a mutation at amino acid position 75 (appendix B). In addition, said mutant is highly active for alkane substrates and supports thousands of product turnovers (abstract).
For the reasons stated herein, the teachings of Arnolf anticipates claims 1, 3, 13-19.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Osbourne et al (US 2017/0247667 A1, Date Published: Aug. 31, 2017, cited on IDS dated 9/18/2024) {herein Osbourne ‘667} in view of Osbourne et al (US 9,708,587 B2, Date of Publication: Jul. 18, 2017, Examiner cited) {herein Osbourne ‘587}. Claim 13 is rejected as it reads on the elected species SEQ ID NO: 680.
Claims 13 is drawn to the engineered cytochrome P450-BM3 variant of Claim 1, wherein said engineered cytochrome P450-BM3 variant comprises a polypeptide sequence that:(a) is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the sequence of at least one engineered cytochrome P450-BM3 variant set forth in Table 2.2, 4.1, 5.1, 5.2, 6.1, 7.1, 7.3, 8.1, 9.1, 10.1, 11.2, 12.1, 12.2, 12.3, 13.1, and 14.1; (b) is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to SEQ ID NO: 680; (c) comprises a sequence set forth in SEQ ID NO: 680; (d) is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the sequence of at least one engineered cytochrome P450-BM3 variant set forth in the even numbered sequences of SEQ ID NO680; and/or (e) comprises a polypeptide sequence forth in at least one of the even numbered sequences of SEQ ID NO: 680.
The teachings of Osbourne ‘667 as applied to claims 1, 14-19.
However, Osbourne ‘667 does not teach the engineered cytochrome P450-BM3 variant of Claim 1, wherein said engineered cytochrome P450-BM3 variant comprises a polypeptide sequence that:(a) is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% (b) is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to SEQ ID 680; (c) comprises a sequence set forth in SEQ ID NO: 680; (d) is at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to the sequence of at least one engineered cytochrome P450-BM3 variant set forth in the even numbered sequences of SEQ ID NO: 680; and/or (e) comprises a polypeptide sequence forth in at least one of the even numbered sequences of SEQ ID NO: 680 (claim 13).
With respect to claim 13, Osbourne ‘587 teaches a composition comprising P450-BM3 variant that has at least 96.8% sequence identity to the instant application SEQ ID NO: 680 that exhibits improved activity over a wide range of substrates (appendix C, abstract; column 1, lines 54-59).
Before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to apply the teachings of Osbourne et al ‘667 of a composition comprising P450-BM3 variant with at least one substitution that exhibits improved activity over a wide range of substrates (abstract, para 0004, appendix A) or combine the teachings of Osbourne et al ‘587 because Osbourne ‘587 teaches a composition comprising P450-BM3 variant that has at least 96.8% sequence identity to the instant application SEQ ID NO: 680 that exhibits improved activity over a wide range of substrates (appendix F, abstract; column 1, lines 54-59).
One of ordinary skill in the art would be motivated to either use the teachings of Osbourne ‘667 or combine the teachings of Osbourne ‘587 because Osbourne ‘587 provides the motivation for Osbourne ‘667 to combine SEQ ID NO: 6 (99.3% sequence identity to the instant application SEQ ID NO: 92) with SEQ ID NO: 58 (96.8% sequence identity to the instant application SEQ ID NO: 680), the cytochrome P450 monoxygenase taught by Osbourne ‘587, as one of ordinary skill in the art would expect said composition to provide higher levels of enzymatic activity over a wide range of substrates than if SEQ ID NO: 6 (99.3% sequence identity to the instant application SEQ ID NO: 92) were solely expressed. MPEP 2144.06.I states “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious).” One of ordinary skill in the art knowing the benefit of cytochrome P450 monoxygenase for the manipulation of biotechnological processes would have a reasonable expectation of success that combining the P40 enzyme taught by Osbourne ‘667 with the P40 enzyme taught by Osbourne ‘587 would result in improved activity than if the P40 enzymes were expressed solely because Osbourne ‘667 teaches the combination of analogous mutations/positions should impart improvements in P450 enzymes (para 0118).
One of skill in the art would have a reasonable expectation of success to make and use the claimed cytochrome P450 monoxygenase variants because Osbourne ‘667 provides the basic enzyme and its uses and methods of making it. Whereas Osbourne ‘587 provides the teaching of a composition comprising P450-BM3 variant that has at least 96.8% sequence identity to the instant application SEQ ID NO: 680 that exhibits improved activity over a wide range of substrates (appendix B, abstract; column 1, lines 54-59). Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 3, 13-19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-4, 13, 21-22, 24-26 U.S. Patent Application No. US 18516054 (054’) which are commonly owned and have seven common inventors and filed before the instant application. Although the claims at issue are not identical, they are not patentably distinct from each other because claims1, 3-4, 13, 21-22, 24-26 of 054’ are drawn to a an engineered cytochrome P450-BM3 variant comprising a polypeptide sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more sequence identity to SEQ ID NO: 92 or 680 , or a functional fragment thereof, wherein the polypeptide sequence of said engineered cytochrome P450-BM3 variant comprises at least one substitution or substitution set and wherein the amino acid positions of said polypeptide sequence are numbered with reference to SEQ ID NO: 92 or 680.
The instant application claims 1, 16 are not patentably distinct from claim 1 of ‘054 because claim 1 of ‘054 recites ‘an engineered cytochrome P450-BM3 variant comprising a polypeptide sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more sequence identity to SEQ ID NO: 36, 4, 66, 72, 198, 226, 244, 286, 358, 410, 534, 734, 748, 828, 968, 984, 1160, or 1266, or a functional fragment thereof, wherein the polypeptide sequence of said engineered cytochrome P450-BM3 variant comprises at least one substitution or substitution set and wherein the amino acid positions of said polypeptide sequence are numbered with reference to SEQ ID NO: 36, 4, 66, 72, 198, 226, 244, 286, 358, 410, 534, 734, 748, 828, 968, 984, 1160, or 1266’ which is not patentably distinct from the instant application claims 1, 16 since the instant application SEQ ID NO: 92 is 99% identical to SEQ ID NO: 36 of ‘054 (appendix D).
The instant application claim 3 is not patentably distinct from claim 3 of ‘054 because claim 3 of ‘054 recites ‘the engineered cytochrome P450-BM3 variant of claim 1, wherein said polypeptide sequence has at least 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more sequence identity to SEQ ID NO: 36, and wherein the polypeptide sequence of said engineered cytochrome P450-BM3 variant comprises at least one substitution or substitution set at one or more positions in said polypeptide sequence selected from 75, 75/374, 75/374/458/726, 75/374/726, 75/458, 75/458/726, 75/726, 111/114, 111/603/604/623/853, 111/623, 374/726, and 726, wherein the amino acid positions of said polypeptide sequence are numbered with reference to SEQ ID NO: 36’ which is not patentably distinct from the instant application claim 3 since the instant application SEQ ID NO: 92 is 99% identical to SEQ ID NO: 36 of ‘054 (appendix D).
The instant application claim 13 is not patentably distinct from claim 13 of ‘054 because claim 13 of ‘054 recites ‘the engineered cytochrome P450-BM3 variant of claim 1, wherein said polypeptide sequence has at least 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more sequence identity to SEQ ID NO: 734, and wherein the polypeptide sequence of said engineered cytochrome P450-BM3 variant comprises at least one substitution or substitution set at one or more positions in said polypeptide sequence selected from 24, 53, 75, 78, 82, 88, 150, 180, 183, 257, 270, 410/497/557/576/ 814, 410/497/573/576, 410/497/814, 410/557/924, 437, and 497/557, wherein the amino acid positions of said polypeptide sequence are numbered with reference to SEQ ID NO: 734’ which is not patentably distinct from the instant application claim 13 since elected species SEQ ID NO: 680 of the instant application is 96% identical to SEQ ID NO: 734 of ‘054 (appendix E).
The instant application claim 18 is not patentably distinct from claim 4 of ‘054 because claim 4 of ‘054 recites ‘the engineered cytochrome P450-BM3 variant of claim 1, wherein said polypeptide sequence has at least 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more sequence identity to SEQ ID NO: 734, and wherein the polypeptide sequence of said engineered cytochrome P450-BM3 variant comprises at least one substitution or substitution set at one or more positions in said polypeptide sequence selected from 24, 53, 75, 78, 82, 88, 150, 180, 183, 257, 270, 410/497/557/576/ 814, 410/497/573/576, 410/497/814, 410/557/924, 437, and 497/557 358, 437, and 438, wherein the amino acid positions of said polypeptide sequence are numbered with reference to SEQ ID NO: 66’ which is not patentably distinct from the instant application claim 18 since the instant application SEQ ID NO: 92 is 99% identical to SEQ ID NO: 36 of ‘054 (appendix D).The instant application claim 13 is not patentably distinct from claim 13 of ‘054 because claim 13 of ‘054 recites ‘the engineered cytochrome P450-BM3 variant of claim 1, wherein said polypeptide sequence has at least 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more sequence identity to SEQ ID NO: 734, and wherein the polypeptide sequence of said engineered cytochrome P450-BM3 variant comprises at least one substitution or substitution set at one or more
positions in said polypeptide sequence selected from 24, 53, 75, 78, 82, 88, 150, 180, 183, 257, 270, 410/497/557/576/814, 410/497/573/576, 410/497/814, 410/557/924, 437, and 497/557, wherein the amino acid positions of said polypeptide sequence are numbered with reference to SEQ ID NO:
734’ which is not patentably distinct from the instant application claim 13 since elected species SEQ ID NO: 680 of the instant application is 96% identical to SEQ ID NO: 734 of ‘054 (appendix E).
The instant application claim 14 is not patentably distinct from claim 21 of ‘054 because claim 21 of ‘054 recites ‘the engineered cytochrome P450-BM3 variant of claim 1, wherein said engineered cytochrome P450-BM3 variant comprises at least one improved property, as compared to a wild-type
Bacillus megaterium cytochrome P450- BM3 or engineered P450-BM3 variant’ which is not patentably distinct from the instant application claim 14 since the instant application SEQ ID NO: 92 is 99% identical to SEQ ID NO: 36 of ‘054 (appendix D).
The instant application claim 15 is not patentably distinct from claim 22 of ‘054 because claim 22 of ‘054 recites ‘the engineered cytochrome P450-BM3 variant of claim 21, wherein said improved property comprises a property selected from the properties consisting of (a) an improved activity on a substrate, (b) improved thermostability, (c) increased activity on a substrate after preincubation
at 42.5°C and (d) improved stereoselectivity toward one or more diastereomer products’ which is not patentably distinct from the instant application claim 15 since the instant application SEQ ID NO: 92 is 99% identical to SEQ ID NO: 36 of ‘054 (appendix D).
The instant application claim 17 is not patentably distinct from claims 24-25 of ‘054 because claims 24-25 of ‘054 recites ‘a polynucleotide sequence encoding at least one engineered cytochrome P450-BM3 variant of claim 20, said polynucleotide sequence comprises at least 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more sequence identity to SEQ ID NOS: 3, 35, 65, 71,197,225,243,285,357, 40, 533,733,747,827, 967, 983, 1159, or 1265, wherein the polynucleotide sequence of said engineered cytochrome P450-BM3 variant comprises at least one substitution at one or more positions’ (claim 24) and ‘an expression vector comprising at least one polynucleotide sequence of claim 24’ (claim 25) which is not patentably distinct from the instant application claim 17 since SEQ ID NO 3 of ‘054 is the polynucleotide sequence of SEQ ID NO: 36 of ‘054 which is 99% identical to the instant application SEQ ID NO: 92 (appendix D).
The instant application claim 19 is not patentably distinct from claim 26 of ‘054 because claim 26 of ‘054 recites ‘a host cell comprising at least one polynucleotide sequence of claim 24. which is not patentably distinct from the instant application claim 17’ which is not patentably distinct from the instant application claim 19 since the instant application SEQ ID NO: 92 is 99% identical to SEQ ID NO: 36 of ‘054 (appendix D).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Status of Claims
Claims 1, 3, 13-19 are pending.
Claims 2, 4-12, 20 stands withdrawn pursuant to 37 CFR 1.142(b).
Claims 1, 3, 13-19 are rejected.
No claims are in condition for allowance.
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/ERICA NICOLE JONES-FOSTER/Examiner, Art Unit 1656
/MANJUNATH N RAO/Supervisory Patent Examiner, Art Unit 1656
Appendix A
Osbourne et al ‘667 SEQ ID NO: 6 #2 (STIC Search result # 151) vs Instant Application SEQ ID NO: 92
Query Match 99.3%; Score 5425; Length 1049;
Best Local Similarity 99.5%;
Matches 1044; Conservative 0; Mismatches 5; Indels 0; Gaps 0;
Qy 1 MTIKEMPQPKTFGELKNLPLLNTDKPVQALMRIADELGEIFKFEAPGSVTRFLSSQRLIK 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MTIKEMPQPKTFGELKNLPLLNTDKPVQALMRIADELGEIFKFEAPGSVTRFLSSQRLIK 60
Qy 61 EACDESRFDKNLSQALKFARDFLGDGLFTSWTHEPNWKKAHNILGPSFSQRAMKRYHAMM 120
|||||||||||||||||||||||||||||||||||||||||||| |||||||||||||||
Db 61 EACDESRFDKNLSQALKFARDFLGDGLFTSWTHEPNWKKAHNILLPSFSQRAMKRYHAMM 120
Qy 121 VDIAVQLVQKWERLNADEHIEVSEDMTRLTLDTIGLCGFNYRFNSFYRDQPHPFIVSMVR 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 VDIAVQLVQKWERLNADEHIEVSEDMTRLTLDTIGLCGFNYRFNSFYRDQPHPFIVSMVR 180
Qy 181 ALDEVMNKLQRANPDDPAYDENKRQCQEDIKVMNDYVDKIIADRKARGEQSHDLLTQMLN 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 ALDEVMNKLQRANPDDPAYDENKRQCQEDIKVMNDYVDKIIADRKARGEQSHDLLTQMLN 240
Qy 241 GKDPETGEPLDDGNIRYQIITFLIAGHETTSGLLSFALYFLVKNPHVLQKVAEEAARVLV 300
||||||||||||||| ||||||||||||||||||||||||||||||||||||||||||||
Db 241 GKDPETGEPLDDGNISYQIITFLIAGHETTSGLLSFALYFLVKNPHVLQKVAEEAARVLV 300
Qy 301 DPVPSYKQVKQLKYVGMVLNEALRLWPTAPAFSLYAKEDTVLGGEYPLTKGDEVMVLIPQ 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 DPVPSYKQVKQLKYVGMVLNEALRLWPTAPAFSLYAKEDTVLGGEYPLTKGDEVMVLIPQ 360
Qy 361 LHRDKTIWGDDVEEFRPERFENPSAIPQHAFKPFGNGQRACIGQQFALHEATLVLGMMLK 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 LHRDKTIWGDDVEEFRPERFENPSAIPQHAFKPFGNGQRACIGQQFALHEATLVLGMMLK 420
Qy 421 HFDFEDHTNYELVIKETLTLKPEGFVVKAKSKGIPLGGIPSPSTEQSAKKVRKKAENAHN 480
|||||||||||| ||||||||||||||||||| |||||||||||||||||||||||||||
Db 421 HFDFEDHTNYELDIKETLTLKPEGFVVKAKSKKIPLGGIPSPSTEQSAKKVRKKAENAHN 480
Qy 481 TPLLVLYGSNAGTAEGTARDLADIAMSKGFAPQVATLDSHAGNLPREGAVLIVTASYNGH 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 TPLLVLYGSNAGTAEGTARDLADIAMSKGFAPQVATLDSHAGNLPREGAVLIVTASYNGH 540
Qy 541 PPDNAKQFVDWLDQASADEVKGVRYSVFGCGDKNWAATYQKVPAFIDETLAAKGAENIAD 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 PPDNAKQFVDWLDQASADEVKGVRYSVFGCGDKNWAATYQKVPAFIDETLAAKGAENIAD 600
Qy 601 RGEADASDDFEGTYEEWRDHMWSDVAAYFNLDIENSEDNKSTLSLQFVDSAADMPLAKMH 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 RGEADASDDFEGTYEEWRDHMWSDVAAYFNLDIENSEDNKSTLSLQFVDSAADMPLAKMH 660
Qy 661 GAFSTNVVASKELQQPGSARSTRHLEIELPKEASYQEGDHLGVIPRNYEGIVNRVTARFG 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 GAFSTNVVASKELQQPGSARSTRHLEIELPKEASYQEGDHLGVIPRNYEGIVNRVTARFG 720
Qy 721 LSASQQIRLEAEEEKLAHLPLAKTVSVEELLQYVELQDPVTRTQLRAMAAKTVCPPHKVE 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 LSASQQIRLEAEEEKLAHLPLAKTVSVEELLQYVELQDPVTRTQLRAMAAKTVCPPHKVE 780
Qy 781 LEALLEKQAYKEQVLAKRLTMLELLEKYPACEMKFSEFIALLPSIRPRYYSISSSPRVDE 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 LEALLEKQAYKEQVLAKRLTMLELLEKYPACEMKFSEFIALLPSIRPRYYSISSSPRVDE 840
Qy 841 KQASITVSVVSGPAWSGYGEYKGIASNYLAELQEGDTITCFISTPQSEFTLPKDPETPLI 900
|||||||||||| |||||||||||||||||||||||||||||||||||||||||||||||
Db 841 KQASITVSVVSGEAWSGYGEYKGIASNYLAELQEGDTITCFISTPQSEFTLPKDPETPLI 900
Qy 901 MVGPGTGVAPFRGFVQARKQLKEQGQSLGEAHLYFGCRSPHEDYLYQEELENAQSEGIIT 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 MVGPGTGVAPFRGFVQARKQLKEQGQSLGEAHLYFGCRSPHEDYLYQEELENAQSEGIIT 960
Qy 961 LHTAFSRMPNQPKTYVQHVMEQDGKKLIELLDQGAHFYICGDGSQMAPAVEATLMKSYAD 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 LHTAFSRMPNQPKTYVQHVMEQDGKKLIELLDQGAHFYICGDGSQMAPAVEATLMKSYAD 1020
Qy 1021 VHQVSEADARLWLQQLEEKGRYAKDVWAG 1049
|||||||||||||||||||||||||||||
Db 1021 VHQVSEADARLWLQQLEEKGRYAKDVWAG 1049
Appendix B
Arnold et al SEQ ID NO: 44 (STIC Search Result No. 45) vs Instant Application SEQ ID NO: 92 (L75W)
Query Match 97.7%; Score 5336; Length 1048;
Best Local Similarity 98.0%;
Matches 1027; Conservative 5; Mismatches 16; Indels 0; Gaps 0;
Qy 2 TIKEMPQPKTFGELKNLPLLNTDKPVQALMRIADELGEIFKFEAPGSVTRFLSSQRLIKE 61
||||||||||||||||||||||||||||||:||||||||||||||| |||:|||||||||
Db 1 TIKEMPQPKTFGELKNLPLLNTDKPVQALMKIADELGEIFKFEAPGCVTRYLSSQRLIKE 60
Qy 62 ACDESRFDKNLSQALKFARDFLGDGLFTSWTHEPNWKKAHNILGPSFSQRAMKRYHAMMV 121
|||||||||||||| |||||| ||||||||||| ||||||||| |||||:||| ||||||
Db 61 ACDESRFDKNLSQAWKFARDFAGDGLFTSWTHEINWKKAHNILLPSFSQQAMKGYHAMMV 120
Qy 122 DIAVQLVQKWERLNADEHIEVSEDMTRLTLDTIGLCGFNYRFNSFYRDQPHPFIVSMVRA 181
||||||||||||||||||||||||||||||||||||||||||||||||||||||:|||||
Db 121 DIAVQLVQKWERLNADEHIEVSEDMTRLTLDTIGLCGFNYRFNSFYRDQPHPFIISMVRA 180
Qy 182 LDEVMNKLQRANPDDPAYDENKRQCQEDIKVMNDYVDKIIADRKARGEQSHDLLTQMLNG 241
|||||||||||||||||||||||||||||||||| ||||||||||||||| |||||||||
Db 181 LDEVMNKLQRANPDDPAYDENKRQCQEDIKVMNDLVDKIIADRKARGEQSDDLLTQMLNG 240
Qy 242 KDPETGEPLDDGNIRYQIITFLIAGHETTSGLLSFALYFLVKNPHVLQKVAEEAARVLVD 301
|||||||||||||| |||||||||||||||||||||||||||||||||||||||||||||
Db 241 KDPETGEPLDDGNISYQIITFLIAGHETTSGLLSFALYFLVKNPHVLQKVAEEAARVLVD 300
Qy 302 PVPSYKQVKQLKYVGMVLNEALRLWPTAPAFSLYAKEDTVLGGEYPLTKGDEVMVLIPQL 361
||||||||||||||||||||||||||||||||||||||||||||||| ||||||||||||
Db 301 PVPSYKQVKQLKYVGMVLNEALRLWPTAPAFSLYAKEDTVLGGEYPLEKGDEVMVLIPQL 360
Qy 362 HRDKTIWGDDVEEFRPERFENPSAIPQHAFKPFGNGQRACIGQQFALHEATLVLGMMLKH 421
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 HRDKTIWGDDVEEFRPERFENPSAIPQHAFKPFGNGQRACIGQQFALHEATLVLGMMLKH 420
Qy 422 FDFEDHTNYELVIKETLTLKPEGFVVKAKSKGIPLGGIPSPSTEQSAKKVRKKAENAHNT 481
||||||||||| ||||||||||||||||||| ||||||||||||||||||||||||||||
Db 421 FDFEDHTNYELDIKETLTLKPEGFVVKAKSKKIPLGGIPSPSTEQSAKKVRKKAENAHNT 480
Qy 482 PLLVLYGSNAGTAEGTARDLADIAMSKGFAPQVATLDSHAGNLPREGAVLIVTASYNGHP 541
||||||||| ||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 PLLVLYGSNMGTAEGTARDLADIAMSKGFAPQVATLDSHAGNLPREGAVLIVTASYNGHP 540
Qy 542 PDNAKQFVDWLDQASADEVKGVRYSVFGCGDKNWAATYQKVPAFIDETLAAKGAENIADR 601
||||||||||||||||||||||||||||||||||| ||||||||||||||||||||||||
Db 541 PDNAKQFVDWLDQASADEVKGVRYSVFGCGDKNWATTYQKVPAFIDETLAAKGAENIADR 600
Qy 602 GEADASDDFEGTYEEWRDHMWSDVAAYFNLDIENSEDNKSTLSLQFVDSAADMPLAKMHG 661
|||||||||||||||||:||||||||||||||||||||||||||||||||||||||||||
Db 601 GEADASDDFEGTYEEWREHMWSDVAAYFNLDIENSEDNKSTLSLQFVDSAADMPLAKMHG 660
Qy 662 AFSTNVVASKELQQPGSARSTRHLEIELPKEASYQEGDHLGVIPRNYEGIVNRVTARFGL 721
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 AFSTNVVASKELQQPGSARSTRHLEIELPKEASYQEGDHLGVIPRNYEGIVNRVTARFGL 720
Qy 722 SASQQIRLEAEEEKLAHLPLAKTVSVEELLQYVELQDPVTRTQLRAMAAKTVCPPHKVEL 781
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 DASQQIRLEAEEEKLAHLPLAKTVSVEELLQYVELQDPVTRTQLRAMAAKTVCPPHKVEL 780
Qy 782 EALLEKQAYKEQVLAKRLTMLELLEKYPACEMKFSEFIALLPSIRPRYYSISSSPRVDEK 841
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 EALLEKQAYKEQVLAKRLTMLELLEKYPACEMKFSEFIALLPSIRPRYYSISSSPRVDEK 840
Qy 842 QASITVSVVSGPAWSGYGEYKGIASNYLAELQEGDTITCFISTPQSEFTLPKDPETPLIM 901
||||||||||| ||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 QASITVSVVSGEAWSGYGEYKGIASNYLAELQEGDTITCFISTPQSEFTLPKDPETPLIM 900
Qy 902 VGPGTGVAPFRGFVQARKQLKEQGQSLGEAHLYFGCRSPHEDYLYQEELENAQSEGIITL 961
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 VGPGTGVAPFRGFVQARKQLKEQGQSLGEAHLYFGCRSPHEDYLYQEELENAQSEGIITL 960
Qy 962 HTAFSRMPNQPKTYVQHVMEQDGKKLIELLDQGAHFYICGDGSQMAPAVEATLMKSYADV 1021
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 HTAFSRMPNQPKTYVQHVMEQDGKKLIELLDQGAHFYICGDGSQMAPAVEATLMKSYADV 1020
Qy 1022 HQVSEADARLWLQQLEEKGRYAKDVWAG 1049
||||||||||||||||||||||||||||
Db 1021 HQVSEADARLWLQQLEEKGRYAKDVWAG 1048
Appendix C
Osbourne et al ‘587 SEQ ID NO: 58 (STIC Search Result No: 1) vs Instant Application SEQ ID NO: 680
Query Match 96.8%; Score 5294; Length 1049;
Best Local Similarity 97.3%;
Matches 1021; Conservative 4; Mismatches 24; Indels 0; Gaps 0;
Qy 1 MTIKEMPQPKTFGELKNLPLLNTDKPVQALMRIADELGEIFKFEAPGSVTRFLSSQRLIK 60
||||||||||||||||||||||||||||||||||||||||||||||| |||:||||||||
Db 1 MTIKEMPQPKTFGELKNLPLLNTDKPVQALMRIADELGEIFKFEAPGCVTRYLSSQRLIK 60
Qy 61 EACDESRFDKNLSQGLKFARDFLGDGLFTSWTHEPNWKKAHNILGPSFSQLAMGRYHAMM 120
|||||||||||||| ||||||| |||| |||||||||||||||| ||||| || ||||||
Db 61 EACDESRFDKNLSQALKFARDFAGDGLVTSWTHEPNWKKAHNILLPSFSQQAMKRYHAMM 120
Qy 121 VDIAVQLVQKWERLNADEHIEVSEDMTRLTLDTIGLCGFNYRFNSFYRDQPHPFIVSVEG 180
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||:
Db 121 VDIAVQLVQKWERLNADEHIEVSEDMTRLTLDTIGLCGFNYRFNSFYRDQPHPFIVSMVR 180
Qy 181 ALDEVMNKLQRANPDDPAYDENKRQCQEDIKVMNDYVDKIIADRKARGEQSHDLLTQMLN 240
||||||||||||||||||||||||||||||||||| ||||||||||||||||||||||||
Db 181 ALDEVMNKLQRANPDDPAYDENKRQCQEDIKVMNDLVDKIIADRKARGEQSHDLLTQMLN 240
Qy 241 GKDPATGEPLDDGNIRYQILTFLIAGHETTSGLLSFALYFLVKNPHVLQKVAEEAARVLV 300
|||| |||||||||| |||:||||||||||||||||||||||||||||||||||||||||
Db 241 GKDPETGEPLDDGNISYQIITFLIAGHETTSGLLSFALYFLVKNPHVLQKVAEEAARVLV 300
Qy 301 DPVPSYKQVKQLKYVGMVLNEALRLWPTAPAFSLYAKEDTVLGGEYPLTKGDEVMVLIPQ 360
|||||||||||||||||||||||||||||||||||||||||||||||| |||||||||||
Db 301 DPVPSYKQVKQLKYVGMVLNEALRLWPTAPAFSLYAKEDTVLGGEYPLEKGDEVMVLIPQ 360
Qy 361 LHRDKTIWGDDVEEFRPERFENPSAIPQHAFKPFGNGQRACIGWQFALHEATLVLGMMLK 420
||||||||||||||||||||||||||||||||||||||||||| ||||||||||||||||
Db 361 LHRDKTIWGDDVEEFRPERFENPSAIPQHAFKPFGNGQRACIGQQFALHEATLVLGMMLK 420
Qy 421 HFDFEDHTNYELVIKEKLTLKPEGFVVKAKSKGIPLGLIPSPSTEQSAKKVRKKAENAHN 480
|||||||||||| ||| ||||||||||||||| |||| ||||||||||||||||||||||
Db 421 HFDFEDHTNYELDIKETLTLKPEGFVVKAKSKKIPLGGIPSPSTEQSAKKVRKKAENAHN 480
Qy 481 TPLLVLYGSNAGTAEGTARDLADIAMSKGFAPQVATLDSHAGNLPREGAVLIVTASYNGH 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 TPLLVLYGSNAGTAEGTARDLADIAMSKGFAPQVATLDSHAGNLPREGAVLIVTASYNGH 540
Qy 541 PPDNAKQFVDWLDQASADEVKGVRYSVFGCGDKNWAATYQKVPAFIDETLAAKGAENIAD 600
|||||||||||||||||||||||||||||||||||| |||||||||||||||||||||||
Db 541 PPDNAKQFVDWLDQASADEVKGVRYSVFGCGDKNWATTYQKVPAFIDETLAAKGAENIAD 600
Qy 601 RGEADASDDFEGAYEEWSDHMWSDVAAYFNLDIENSEDNKSTLSLQFVDSAADMPLAKMH 660
|||||||||||| |||| :|||||||||||||||||||||||||||||||||||||||||
Db 601 RGEADASDDFEGTYEEWREHMWSDVAAYFNLDIENSEDNKSTLSLQFVDSAADMPLAKMH 660
Qy 661 GAFSTNVVASKELQQPGSARSTRHLEIELPKEASYQEGDHLGVIPRNYEGIVNRVTARFG 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 GAFSTNVVASKELQQPGSARSTRHLEIELPKEASYQEGDHLGVIPRNYEGIVNRVTARFG 720
Qy 721 LSASQQIRLEAEEEKLAHLPLAKTVSVEELLQYVELQDPVTRTQLRAMAAKTVCPPHKVE 780
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 LDASQQIRLEAEEEKLAHLPLAKTVSVEELLQYVELQDPVTRTQLRAMAAKTVCPPHKVE 780
Qy 781 LEALLEKQAYKEQVLAKRLTMLELLEKYPACEMKFSEFIALLPSIRPRYYSISSSPRVDE 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 LEALLEKQAYKEQVLAKRLTMLELLEKYPACEMKFSEFIALLPSIRPRYYSISSSPRVDE 840
Qy 841 KQASITVSVVSGPAWSGYGEYKGIASNYLAELQEGDTITCFISTDQSEFTLPKDPETPLI 900
|||||||||||| ||||||||||||||||||||||||||||||| |||||||||||||||
Db 841 KQASITVSVVSGEAWSGYGEYKGIASNYLAELQEGDTITCFISTPQSEFTLPKDPETPLI 900
Qy 901 MVGPGTGVAPFRGFVQARKQLKEQGQSLGEAHLYFGCRSPHEDYLYQEELENAQSEGIIT 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 MVGPGTGVAPFRGFVQARKQLKEQGQSLGEAHLYFGCRSPHEDYLYQEELENAQSEGIIT 960
Qy 961 LHTAFSRMPNQPKTYVQHVMEQDGKKLIELLDQGAHFYICGDGSQMAPAVEATLMKSYAD 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 LHTAFSRMPNQPKTYVQHVMEQDGKKLIELLDQGAHFYICGDGSQMAPAVEATLMKSYAD 1020
Qy 1021 VHQVSEADARLWLQQLEEKGRYAKDVWAG 1049
|||||||||||||||||||||||||||||
Db 1021 VHQVSEADARLWLQQLEEKGRYAKDVWAG 1049
Appendix D
Instant Application SEQ ID NO: 92 ABSS alignment with US 18516054 SEQ ID NO: 36
PNG
media_image1.png
916
421
media_image1.png
Greyscale
Appendix E
Instant Application SEQ ID NO: 680 ABSS alignment with US 18516054 SEQ ID NO: 734
PNG
media_image2.png
909
416
media_image2.png
Greyscale
Prosecution Insights