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 .
Support for the amendments is within the instant application specification.
Applicant’s amendment to the claims filed on 5/7/2026 in response to the Non-Final Rejection mailed on 11/7/2025 is acknowledged. This listing of claims replaces all prior listings of claims in the application.
Claims 11, 13-15, 19-28 are pending.
Claims 1-10, 12, 16-18 are canceled.
Applicant’s remarks filed on 5/7/2026 in response to the Non-Final Rejection mailed on 11/7/2025 have been fully considered and are deemed persuasive to overcome at least one of the rejections and/or objections as previously applied.
The text of those sections of Title 35 U.S. Code not included in the instant action can be found in the prior Office Action.
Withdrawn Rejections
The rejection of claims 11, 13-15, 19-28 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ) is withdrawn in view of Applicant’s amendment of claim 11 to recite ‘wherein the HMGR comprises a full length amino acid sequence having at least 90% amino acid identity with SEQ ID NO:3 or SEQ ID NO: 4 and a conserved domain having an amino acid sequence TAVNGILGRGK (SEQ ID NO:7), the MK comprises a full length amino acid sequence having at least 90% amino acid identity with SEQ ID NO: 1 or SEQ ID NO:2’; claim 22 to recite ‘wherein the HMGR comprises a full length amino acid sequence having at least 95% amino acid identity with SEQ ID NO:3 or SEQ ID NO:4, and the MK comprises a full length amino acid sequence having at least 95% amino acid identity with SEQ ID NO:1 or SEQ ID NO:2’; claim 23 to recite ‘wherein the HMGR comprises a full length amino acid sequence having at least 99"% amino acid identity with SEQ ID NO:3 or SEQ ID NO:4, and the MK comprises a full length amino acid sequence having at least 99% amino acid identity with SEQ ID NO:1 or SEQ ID NO:2.’
The scope of enablement rejection of claims 11, 13-15, 19-28 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ) is withdrawn in view of Applicant’s amendment of claim 11 to recite ‘wherein the HMGR comprises a full length amino acid sequence having at least 90% amino acid identity with SEQ ID NO:3 or SEQ ID NO: 4 and a conserved domain having an amino acid sequence TAVNGILGRGK (SEQ ID NO:7), the MK comprises a full length amino acid sequence having at least 90% amino acid identity with SEQ ID NO: 1 or SEQ ID NO:2’; claim 22 to recite ‘wherein the HMGR comprises a full length amino acid sequence having at least 95% amino acid identity with SEQ ID NO:3 or SEQ ID NO:4, and the MK comprises a full length amino acid sequence having at least 95% amino acid identity with SEQ ID NO:1 or SEQ ID NO:2’; claim 23 to recite ‘wherein the HMGR comprises a full length amino acid sequence having at least 99% amino acid identity with SEQ ID NO:3 or SEQ ID NO:4, and the MK comprises a full length amino acid sequence having at least 99% amino acid identity with SEQ ID NO:1 or SEQ ID NO:2.’
The rejection of claim 23 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph is withdrawn in view of Applicant’s amendment of claim 23 to recite ‘wherein the HMGR comprises a full length amino acid sequence having at least 99% amino acid identity with SEQ ID NO:3 or SEQ ID NO:4, and the MK comprises a full length amino acid sequence having at least 99% amino acid identity with SEQ ID NO:1 or SEQ ID NO:2.’
Maintained 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.
The rejection of claims 11, 13-15, 19-28 under 35 U.S.C. 103 as being unpatentable over Demain et al. (1967, Journal of Bacteriology, https://journals.asm.org/journal/jb on 15 April 2024 by 151.207.250.216, cited on IDS filed 4/8/2022) {herein Demain} in view of Garsin et al (Date Published: April 2010, NIH Public Access, cited on PTO-892 dated 11/7/2025) {herein Garsin}, Harada et al. (JP2009207376A, priority to 03-03-2008, previously cited in PTO-892 filed 9/25/2023; machine translation generated in Espacenet) {herein Harada} and Masinani et al. (WO 02/094868 A2, Date of Publication: 28 November 2002, previously cited in PTO-892 dated 5/7/2024) {herein Masignani} as evidenced by Voynova et al (2003, Journal of Bacteriology, Examiner cited) {herein Voynova}, GenBank WP_012730718.1 (26 May 2013, https://www.ncbi.nlm.nih.gov/protein/WP_012730718.1, previously cited in PTO-892 filed 5/7/2024) {herein Genbank WP_012730718.1}, Gronenberg et al. (2013, SciVerse ScienceDirect, http://dx.doi.org/10.1016/j.cbpa.2013.03.037, previously cited in PTO-892 filed 5/7/2024) {herein Gronenberg} and Andressi et al (2009, NIH Public Access, cited on PTO-892 dated 11/7/2025) {herein Andressi} is maintained. The rejection has been modified in view of Applicant’s amendment of claim 11 to recite ‘wherein the IL is an imidazolium, cholinium, or diethanolamine [DEOA] IL’; amendment of claim 26 to recite ‘wherein the IL is an imidazolium IL’; amendment of claim 27 to recite ‘wherein the IL comprises a cholinium IL.’
Claims 11, 13-15, 19-28 are drawn to a method for a genetically modified bacterial host cell producing tetramethyl pyrazine (TMP), comprising (a) providing a genetically modified Corynebacterium host cell comprising the enzymes: acetyl-CoA acetyltransferase (AtoB), hydroxymethylglutaryl-CoA synthase (HMGS), 3- hydroxy-3-methylglutaryl-CoA reductase (HMGR), mevalonate kinase (MK),and/or phosphomevalonate decarboxylase (PMD); wherein the HMGR comprises a full length amino acid sequence having at least 90% amino acid identity with SEQ ID NO:3 or SEQ ID NO: 4 and a conserved domain having an amino acid sequence TAVNGILGRGK (SEQ ID NO:7), the MK comprises a full length amino acid sequence having at least 90% amino acid identity with SEQ ID NO: 1 or SEQ ID NO:2, and an amino acid sequence RGLGSSAA (SEQ ID NO:5) in a GHMP kinase N domain and/or KLTGXGRGG (SEQ ID NO:6) in a GHMP kinase C domain, wherein X is any naturally occurring amino acid residue, (b) culturing or growing the host cell in a suitable culture or medium comprising an ionic liquid (IL), such that the host cell produces equal to or more than 5 g of TMP per L of the culture or medium in 48 hours; wherein the IL is an imidazolium, cholinium, or diethanolamine [DEOA] IL.
With respect to claims 11, 20, Demain teaches a method wherein a mutant of Corynebacterium glutamicum was found to accumulate tetramethylpyrazine in the presence of thiamine (abstract). Said strain is a mutant of Corynebacterium glutamicum (i.e. genetically modified) as said strain is not wildtype. Accumulation of tetramethylepyrazine is dependent upon the addition of thiamine (vitamin B) in growth media (abstract). Evidentiary reference of Takeno is cited to demonstrate that Corynebacterium natively contains acetyl-CoA transferase, which is the same as the claimed acetyl-CoA acetyltransferase (claim 11) (page 6779, fig 3 legend). As such, it would be obvious to one of ordinary skill in that art that the mutant of Corynebacterium glutamicum, taught by Demain, natively contains acetyl-CoA acetyltransferase sequence since Demain does not teach said enzyme is deleted from the mutant Corynebacterium glutamicum. Regarding the limitation “such that the host cell produces equal to or more than 5 g of TMP per L of the culture or medium in 48 hours,” (claim 11) this language does not require steps to be and is just the characteristic of the microorganism which characteristic could be inherent. Additionally, MPEP 2144.05 states"[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (MPEP 2144.05 IIA)." One of ordinary skill would desire to optimize the amount of TMP depending on the particular application. It would be routine for one to arrive at the amount for the application they intend on using the TMP. Therefore, the above invention would have been prima facie obvious.
With respect to claim 14, Demain teaches a method wherein TMP is separated from culture by filtration and crystallization (page 324, column 1, paragraph 5).
With respect to claim 21, the strain taught by Demain and the strain within the instant application claim 21 are inherently the same as they belong to the same genus and species. Absent evidence otherwise, it would be obvious to one of ordinary skill in the art that Demain could utilize a genetically modified bacterial strain of ATCC 13032 Corynebacterium glutamicum, as said strain is the same genus and species of the mutant strain Corynebacterium glutamicum taught by Demain.
However, Demain does not teach the method of claim 11 of the host cell comprising enzymes hydroxymethylqlutaryl-CoA synthase (HMGS), 3-hydroxy-3-methylqlutaryl-CoA reductase (HMGR), mevalonate kinase (MK), and/or phosphomevalonate decarboxylase (PMD); wherein the HMGR comprises a full length amino acid sequence having at least 90% amino acid identity with SEQ ID NO:3 or SEQ ID NO:4 and a conserved domain having an amino acid sequence TAVNGILGRGK (SEQ ID NO:7), the MK comprises a full length amino acid sequence having at least 90% amino acid identity with SEQ ID NO:1 or SEQ ID NO:2 and an amino acid sequence RGLGSSAA (SEQ ID NO:5) in a GHMP kinase N domain and/or KLTGXGRGG (SEQ ID NO:6) in a GHMP kinase C domain, wherein X is any naturally occurring amino acid residue; (b) culturing or growing the host cell in a suitable culture or medium comprising an ionic liquid (IL), such that the host cell produces equal to or more than 5 g of TMP per L of the culture or medium in 48 hours; wherein the IL is an imidazolium, cholinium, or diethanolamine [DEOA] IL’ (claim 11). The method of claim 13, wherein step (b) further comprises producing isopentenol (claim 13). ( The method of claim 15, further comprises (c) extracting or separating the isopentenol from the rest of the culture or medium, and/or host cell (claim 15). The method of claim 19, wherein the genetically modified bacterial host cell also produces isopentenol (claim 19). The method of claim 11, wherein the HMGR comprises a full length amino acid sequence having at least 95% amino acid identity with SEQ ID NO:3 or SEQ ID NO:4; and the MK comprises a full length amino acid sequence having at least 95% amino acid identity with SEQ ID NO:1 or SEQ ID NO:2 (claim 22). The method of claim 23, wherein the HMGR comprises a full length amino acid sequence having at least 99% amino acid identity with SEQ ID NO: 3 or SEQ ID NO:4, and the MK comprises a full length amino acid sequence having at least 99% amino acid identity with SEQ ID NO:1 or SEQ ID NO:2 (claim 23). The method of claim 24, HMGR comprises SEQ ID NO:3 or SEQ ID NO:4, and the MK comprises SEQ ID NO:1 or SEQ ID NO:2 (claim 24). The method of claim 25, wherein the culture medium comprises 50 mM to 150 mM of the IL (claim 25). The method of claim 26, wherein the IL is an imidazolium (claim 26). The method of claim 27, wherein the IL comprises a cholinium (claim 27). The method of claim 28, wherein the ionic liquid comprises a diethanolamine [DEOA] cation (claim 28)
With respect to claims 11, 25, 26-28, Garsin teaches a method wherein Corynebacterium species are able to utilize ionic liquid culture medium comprised of Iscove's Modified Dulbecco's Medium (IMDM), which contains choline, (page 9, line 10) or Dulbecco's Modified Eagle's Medium (DMEM), which contains imidazolium (page 9, line 11). When choline is dissolved in water, it acts as a cation and is properly called cholinium. In addition, Garsin teaches different forms of ethanolamine can be used in culture media as Corynebacterium species are able to use the different forms of ethanolamine as a sole source of carbon and/or nitrogen (page 1, para 1; page 10, para 1). Examiner takes the position that the teaching of ‘different forms of ethanolamine’ by Garson includes diethanolamine as diethanolamine is a specific type of ethanolamine within the broader family of ethanolamines (amino alcohols). Garsin further discloses the claimed ionic culture medium except for the culture medium comprises 50 mM to 150 mM of the ionic liquid. However, Examiner takes the position that it would have been obvious to one having ordinary skill in the art at the time the invention was made to find the most appropriate concentration of ionic liquid for the culture medium, since it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 105 USPQ 233.
However, Garsin does not teach the method of claim 11 of host cell comprising enzymes wherein the HMGR comprises a full length amino acid sequence having at least 90% amino acid identity with SEQ ID NO:3 or SEQ ID NO: 4 and a conserved domain having an amino acid sequence TAVNGILGRGK (SEQ ID NO:7), the MK comparises a full length amino acid sequence having at least 90% amino acid identity with SEQ ID NO: 1 or SEQ ID NO:2, and an amino acid sequence RGLGSSAA (SEQ ID NO:5) in a GHMP kinase N domain and/or KLTGXGRGG (SEQ ID NO:6) in a GHMP kinase C domain, wherein X is any naturally occurring amino acid residue (claim 11).The method of claim 13, wherein step (b) further comprises producing isopentenol (claim 13). The method of claim 15, further comprises (c) extracting or separating the isopentenol from the rest of the culture or medium, and/or host cell (claim 15). The method of claim 19, wherein the genetically modified bacterial host cell also produces isopentenol (claim 19). The method of claim 22 wherein the HMGR comprises a full length amino acid sequence having at least 95% amino acid identity with SEQ ID NO:3 or SEQ ID NO:4, and the MK comprises a full length amino acid sequence having at least 95% amino acid identity with SEQ ID NO:1 or SEQ ID NO:2 (claim 22). The method of claim 23, wherein the HMGR comprises a full length amino acid sequence having at least 99"% amino acid identity with SEQ ID NO:3 or SEQ ID NO:4, and the MK comprises a full length amino acid sequence having at least 99% amino acid identity with SEQ ID NO:1 or SEQ ID NO:2 (claim 23). The method of claim 24, wherein the HMGR comprises SEQ ID NO:3 or SEQ ID NO:4, and the MK comprises SEQ ID NO:1 or SEQ ID NO:2 (claim 24).
With respect to claims 11, 13, 15, 19, 22-23, Harada teaches a method wherein a recombinant bacterial strain that produces heterologous isoprenoid enzymes such as MK (referred to as MVA kinase by Harada) and HMGR is provided (referred to as HMG-CoA reductase by Harada) (page 4, para 0009, lines 5; pages 11-12, paragraph 0041, lines 456 - 460) in a culture medium comprised of salt as a substrate for the more efficient production of isoprenoids (para 0011). Masignani teaches MK from Staphylococcus aureus is 100% identical to full length MK of SEQ ID NO: 1 within the instant application (Masignani: claim 1; appendix B) and consists of an amino acid sequence RGLGSSAA, which has 100% identity to SEQ ID NO: 5 (appendix B, highlighted) of the instant application (appendix B). Said MK enzyme has been fully characterized as being very effective in catalyzing phosphorylation of mevalonic acid. Supporting the Examiner’s position is the evidentiary reference of Voynova which is cited to demonstrate that S. aureus mevalonate kinase is very effective in catalyzing phosphorylation of mevalonic acid (page 4, column 2, para 1; page 5, column 2, para 1). Since S. aureus MK is well-known and well-characterized to increase isoprenoid production in cells, it would be obvious to one of ordinary skill in the art to use MK from S. aureus for the over-production of isoprenoid TMP in C. glutamicum because one would have a reasonable expectation that said enzyme would optimize the mevalonate (MVA) pathway for Tetramethylpyrazine (TMP) production by circumventing the feedback inhibition and lowering the catalytic rates that often limit native microbial enzymes, thereby leading to significantly higher TMP yields. Furthermore, the evidentiary reference of GenBank WP_012730718.1 is cited to demonstrate that full-length HMGR is 100% identical to the claimed SEQ ID NO: 4 also having a conserved domain of TAVNGILGRGK (SEQ ID NO: 7) (Appendix A). As such, absent evidence otherwise, it is the Examiner’s position that the enzyme HMGR taught by Harada is the same as (100% identical) the instant application SEQ ID NO: 4 with a conserved domain of TAVNGILGRGK (SEQ ID NO: 7) since the enzyme taught by Harada is unmutated. Harada further teaches a method of producing isoprenoids in bacteria and obtaining it from the culture (para 0023). Evidentiary reference of Gronenberg is cited to demonstrate that isopentenol is an isoprenoid derivative (page 17, column 2, paragraph 1). As such, absent evidence otherwise, it is the Examiner’s position that a cell that produces isoprenoids would necessarily also produce isopentenol since isopentenol is a derivative of isoprenoids. Furthermore, Examiner is interpreting the teaching of ‘obtaining isoprenoid from the culture’ to be the separation of isoprenoid from the culture, as recited in the instant application claim 15.
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 Demain of a method of a mutant of Corynebacterium glutamicum to accumulate tetramethylpyrazine in the presence of thiamine (abstract) or combine the teachings of Garsin, Harada and Masignani because Masignani teaches MK is 100% identical to full length MK of SEQ ID NO: 1 within the instant application (Masignani: claim 1; appendix B) and consists of an amino acid sequence RGLGSSAA, which has 100% identity to SEQ ID NO: 5 (appendix B, highlighted) of the instant application (appendix B). Harada teaches a method wherein a recombinant bacterial strain that produces heterologous isoprenoid enzymes such as MK (referred to as MVA kinase by Harada) and HMGR (SEQ ID NO: 4) are provided (referred to as HMG-CoA reductase by Harada) (page 4, para 0009, lines 5; pages 11-12, paragraph 0041, lines 456 - 460) in a culture medium comprised of salt as a substrate for the more efficient production of isoprenoids (para 0011). Whereas, Garsin teaches a method wherein Corynebacterium species in an ionic liquid culture medium comprised Iscove's Modified Dulbecco's Medium (IMDM), contains choline which acts as a cation and is properly called cholinium, (page 9, line 10) or Dulbecco's Modified Eagle's Medium (DMEM), which contains imidazolium (page 9, line 11). In addition, Garsin teaches different forms of ethanolamine can be used in culture media as Corynebacterium species are able to use the different forms of ethanolamine as a sole source of carbon and/or nitrogen (page 1, para 1; page 10, para 1). Examiner takes the position that the teaching of ‘different forms of ethanolamine’ by Garson includes diethanolamine as diethanolamine is a specific type of ethanolamine within the broader family of ethanolamines (amino alcohols).
One of ordinary skill in the art would be motivated to either use the teachings of Demain et al. by itself or combine the teachings of Garsin, Harada and Masignani because Garsin provides the motivation for Demain to utilize an ionic liquid containing different forms of ethanolamine since Garsin teaches Corynebacterium species are able to use the different forms of ethanolamine as a sole source of carbon and/or nitrogen (page 1, para 1). Additionally, since only a select variety of bacteria are able to use ethanolamine as a carbon source (Garsin: abstract) said ionic compound could serve as a means for limiting the growth of contaminants. Furthermore, Demain would be motivated to modify the genetically modified Corynebacteium by adding heterologous isoprenoid enzymes such as MK (SEQ ID NO: 1) (referred to as MVA kinase by Harada) (Masignani: appendix B) and HMGR (referred to as HMG-CoA reductase by Harada) (Harada: pages 11-12, paragraph 0041, lines 456 – 460, appendix A) to the culture medium taught by Garsin because the expression of said genes in heterologous bacteria have been shown to result in the production of Isoprenoids (Harada: para 0001, 0009). Furthermore, since HMGR is from Corynebacterium (SEQ ID NO: 4) (appendix A) one of ordinary skill in the art would expect limited to no deleterious effects from the recombination of the heterologous genes and the appropriate expression of TMP and isopentenol. One of ordinary skill in the art would have a reasonable expectation of success to make and use a culture medium comprising an ionic liquid and a genetically modified bacterial host cell capable of producing tetramethyl pyrazine comprising the enzymes 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), mevalonate kinase (MK) because doing so would result in a culture medium wherein the isoprenoids (HMGR and MK) along with the ionic liquid within the culture medium would serve as a continuous carbon source for the production of TMP, thereby bypassing the need for the continuous replenishment of a carbon source in cultures for the production of TMP.
One of skill in the art would have a reasonable expectation of success to make and use the claimed method for producing TMP because Demain provides the basic method for producing TMP in genetically modified Corynebacterium and its uses and methods of making it. Reference of Garsin provides the teaching of a method wherein Corynebacterium species are able to utilize ionic liquid culture medium comprised of Iscove's Modified Dulbecco's Medium (IMDM), which contains choline, (page 9, line 10) or Dulbecco's Modified Eagle's Medium (DMEM), which contains imidazolium (page 9, line 11) and different forms of ethanolamine can be used in culture media as Corynebacterium species are able to use the different forms of ethanolamine as a sole source of carbon and/or nitrogen (page 1, para 1; page 10, para 1). Of which, Examiner takes the position that the teaching of ‘different forms of ethanolamine’ by Garson includes diethanolamine as diethanolamine is a specific type of ethanolamine within the broader family of ethanolamines (amino alcohols). Harada provides a method for the efficient production of isoprenoids (para 0011) from recombinant bacterial strain that produces heterologous isoprenoid enzymes such as MK (referred to as MVA kinase by Harada) and HMGR (SEQ ID NO: 4) is (referred to as HMG-CoA reductase by Harada) (page 4, para 0009, lines 5; pages 11-12, paragraph 0041, lines 456 - 460) in a culture medium comprised of salt. Whereas, Masignani teaches a method wherein MK is 100% identical to full length MK of SEQ ID NO: 1 within the instant application (Masignani: claim 1; appendix B) and consists of an amino acid sequence RGLGSSAA, which has 100% identity to SEQ ID NO: 5 (appendix B, highlighted) of the instant application (appendix B). Therefore there would be a reasonable expectation of success to arrive at the above invention. 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.
RESPONSE TO REMARKS: Applicant's arguments filed 5/7/2026 have been fully considered but they are not persuasive. Beginning on p. 7 of Applicants’ remarks, Applicants in summary contends that None of the cited references, either alone or combined, do not teach, suggest, or motivate a suitable culture or medium comprising ... an imidazolium, cholinium, or diethanolamine [DEOAl IL.
These arguments are found to be not persuasive. Examiner contends that Garsin provides the motivation for Demain to utilize an ionic liquid containing different forms of ethanolamine since Garsin teaches Corynebacterium species are able to use the different forms of ethanolamine as a sole source of carbon and/or nitrogen (page 1, para 1). As such, Examiner maintains that Demain, in view of Garsin, Harada and Masignani teaches a method for a genetically modified bacterial host cell producing tetramethyl pyrazine (TMP) in imidazolium, cholinium, or diethanolamine [DEOA] ionic liquids.
Conclusion
Status of claims
Claims 11, 13-15, 19-28 are pending.
Claims 1-10, 12, 16-18 are canceled.
Claims 11, 13-15, 19-28 are rejected.
No claims are in condition for allowance.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERICA NICOLE JONES-FOSTER whose telephone number is (571)270-0360. The examiner can normally be reached mf 7:30a - 4:30p.
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/ERICA NICOLE JONES-FOSTER/ /MANJUNATH N RAO/ Examiner, Art Unit 1656 Supervisory Patent Examiner, Art Unit 1656 Appendix A
GenBank WP_012730718.1 alignment with SEQ ID NO: 4 (claims 11, 22, 23) with conserved domain SEQ ID NO: 7 highlighted yellow
Query Match 100.0%; Score 1903; Length 369;
Best Local Similarity 100.0%;
Matches 369; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MSDNLYAPIPMSWIGPVHISGNVVSGETAGWNAEDGTQNQESGASYEAVSIPMATYETPL 60
Db 1 MSDNLYAPIPMSWIGPVHISGNVVSGETAGWNAEDGTQNQESGASYEAVSIPMATYETPL 60
Qy 61 WPSVGRGAKVSRYVEGGIRATLVDERMTRSVYFEAPNAGVALRVATELDRRRDELQAVVA 120
Db 61 WPSVGRGAKVSRYVEGGIRATLVDERMTRSVYFEAPNAGVALRVATELDRRRDELQAVVA 120
Qy 121 HASRFAKLIDLHVQYAGNLLFVRFEFTTGDASGHNMVTLASDNLMPWILQQYPELRYGSI 180
Db 121 HASRFAKLIDLHVQYAGNLLFVRFEFTTGDASGHNMVTLASDNLMPWILQQYPELRYGSI 180
Qy 181 SGNYCSDKKATAVNGILGRGKNVVTEMLIPRNVVEERLKTTPEQIADLNVRKNLVGTTLA 240
Db 181 SGNYCSDKKATAVNGILGRGKNVVTEMLIPRNVVEERLKTTPEQIADLNVRKNLVGTTLA 240
Qy 241 GGLRTANAHYANMLLGFYLATGQDAANIVEGSQGITHAEVRDGDLYFSCNLPNLIVGTVG 300
Db 241 GGLRTANAHYANMLLGFYLATGQDAANIVEGSQGITHAEVRDGDLYFSCNLPNLIVGTVG 300
Qy 301 NGKGQGLEVVEENLRRLGCREDRPAGDNARRLAVLCAASVFCGELSLLAAQTNPGELMAA 360
Db 301 NGKGQGLEVVEENLRRLGCREDRPAGDNARRLAVLCAASVFCGELSLLAAQTNPGELMAA 360
Qy 361 HVKIERKGE 369
Db 361 HVKIERKGE 369
Appendix B
Alignment of SEQ ID NO: 1 with Masignani et al SEQ ID NO: 3294 (claim 1) with SEQ ID NO: 5 highlighted in yellow below.
Query Match 100.0%; Score 1566; Length 306;
Best Local Similarity 100.0%;
Matches 306; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MTRKGYGESTGKIILIGEHAVTFGEPAIA VPFNAGKIKVLIEALESGNYSSIKSDVYDGM 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MTRKGYGESTGKIILIGEHAVTFGEPAIA VPFNAGKIKVLIEALESGNYSSIKSDVYDGM 60
Qy 61 LYDAPDHLKSLVNRFVELNNITEPLAVTIQTNLPPSRGLGSSAAVAVAFVRASYDFLGKS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 LYDAPDHLKSLVNRFVELNNITEPLAVTIQTNLPPSRGLGSSAAVAVAFVRASYDFLGKS 120
Qy 121 LTKEELIEKANWAEQIAHGKPSGIDTQTIVSGKPVWFQKGHAETLKTLSLDGYMVVIDTG 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 LTKEELIEKANWAEQIAHGKPSGIDTQTIVSGKPVWFQKGHAETLKTLSLDGYMVVIDTG 180
Qy 181 VKGSTRQAVEDVHKLCEDPQYMSHVKHIGKLVLRASDVIEHHNFEALADIFNECHADLKA 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 VKGSTRQAVEDVHKLCEDPQYMSHVKHIGKLVLRASDVIEHHNFEALADIFNECHADLKA 240
Qy 241 LTVSHDKIEQLMKIGKENGAIA GKLTGAGRGGSMLLLAKDLPTAKNIVKAVEKAGAAHTW 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 LTVSHDKIEQLMKIGKENGAIA GKLTGAGRGGSMLLLAKDLPTAKNIVKAVEKAGAAHTW 300
Qy 301 IENLGG 306
||||||
Db 301 IENLGG 306
Prosecution Insights