HOST CELLS OVEREXPRESSING TRANSLATIONAL FACTORS

§101 §102 §103 §112

DETAILED CORRESPONDENCE Application Status 1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . 2. Applicant’s amendment to the claims filed on 08/10/2026 in response to the Non-Final Rejection mailed on 05/14/2026 is acknowledged. This listing of claims replaces all prior listings of claims in the application. 3. Claims 21-23 are cancelled. 4. New claims 24-32 are added. 5. Claims 1-6, 8-20, and 24-32 are pending. Claims 14-18 stand withdrawn pursuant to 37 CFR 1.142(b). 6. Applicant’s remarks filed on 08/10/2026 in response to the Non-Final Rejection mailed on 05/14/2026 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. Specification 7. The objection to the specification for an embedded hyperlink is withdrawn in view of applicants’ amendment to the specification to remove said hyperlink. Claim Rejections - 35 USC § 112(b) 8. The rejection of claims 1-6, 8-13 and 22-23 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, for lack of antecedent basis is withdrawn in view of applicants’ amendment to the claims to recite “one or more genetic modifications”. 9. The rejection of claims 8 and 13 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, for lack of antecedent basis is withdrawn in view of applicants’ amendment to the claims to remove the phrases “such as” and “preferably”. Claim Rejections - 35 USC § 112(a) 10. The written description rejection of claims 21-23 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, is withdrawn in view of applicants’ amendment to the claims to cancel claims 21-23. 11. The scope of enablement rejection of claims 21-23 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, is withdrawn in view of applicants’ amendment to the claims to cancel claims 21-23. 12. The written description rejection of claims 1-6, 8-13, and 20 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, is maintained for the reasons of record and the reasons set forth below. The rejection has been modified in order to address applicants’ amendment to the claims and to incorporate new claims 24-32. Claims 1-6, 8-13, 20 and 24-32 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. 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. MPEP § 2163 further states that “[s]atisfactory disclosure of a ‘representative number’ depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus…Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are ‘representative of the full variety or scope of the genus,’ or by the establishment of ‘a reasonable structure-function correlation.’ Such correlations may be established ‘by the inventor as described in the specification,’ or they may be ‘known in the art at the time of the filing date.’" The factors considered in the Written Description requirement are (1) level of skill and knowledge in the art, (2) partial structure, (3) physical and/or chemical properties, (4) functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the (5) method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient." MPEP § 2163. As amended, claims 1-6, 8-13, and 24-32 are drawn to a recombinant eukaryotic host cell comprising a heterologous expression cassette expressing a gene of interest (GOI), which host cell is engineered by one or more genetic modifications to increase expression of two or more genes encoding transition initiation factors (TIF genes) of the messenger ribonucleoprotein (mRNP), compared to the host cell prior to the one or more genetic modifications, wherein the TIF genes comprise at least a gene encoding eIF4A and a gene encoding eIF4G, and wherein expression of at least one of the TIF genes is under transcriptional control of a promoter different from the promoter controlling expression of the GOI. As amended, claim 20 is drawn to a polypeptide expression system comprising one or more heterologous expression cassettes expressing two or more TIF genes of the messenger ribnucleoprotein, wherein the TIF genes comprise at least one gene encoding eIF4A and a gene encoding eIF4G, and wherein the polypeptide expression system is a recombinant eukaryotic host cell comprising a heterologous expression cassette comprising a gene of interest (GOI) encoding a protein of interest (POI) with and one or more expression control sequences operably linked to the GOI. In the instant case, the specification discloses an actual reduction to practice of the following representative species of the genus of eukaryotic host cells having increase expression of two or more genes encoding TIF genes as encompassed by the claims (i.e. eukaryotic cells overexpressing eIF4A, eIF4G, eIF4E, PAB1 and RLI1). Other than the disclosed species, the specification fails to provide any other structure of the infinite methods of increasing expression of genes encoding TIF genes as encompassed by the claims. To this end, there is no prior-art or disclosed teaching regarding the structure of the infinite number of mutations, deletions, insertions, modifications by either small molecule, RNAi, genetic modification that results in increased expression of genes encoding TIF, and there is no disclosed or art-recognized correlation between any structure other than the overexpression of the TIF genes to have the desired function. The breadth of the claims encompass any modification to a host cell including modification of any factor that controls the expression of said genes. Given what is known in the art about the likely outcome of substitutions on structure, conservation of structure is not necessarily a surrogate for conservation of function. In this case, there is no disclosed correlation between structure and function. Accordingly, one of skill in the art would not accept the disclosure of eukaryotic cells overexpressing eIF4A, eIF4G, eIF4E, PAB1 and RLI1 as being representative of all genetic modifications to increase expression of TIF genes as encompassed the claims. As such, the specification, taken with the pre-existing knowledge in the art, fails to satisfy the written description requirement of 35 U.S.C. 112(a). RESPONSE TO REMARKS: Beginning on p. 12 of applicants’ remarks, applicants in summary contend that the specification discloses the level of recombinant protein production resulting from the overexpression of different TIF genes. This argument is found to be not persuasive because MPEP 2163.ll.A.3.(a). states "when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the genus]." See Enzo Biochem, S2S F.Sd at 966, 63 USPQ2d at 1615; Noelle V. Ledermon, 355 F.3d 1343,1350, 69 USPQ2d 1508,1514 (Fed. Cir. 2004) (Fed. Cir. 2004)". In the instant case, while the specification discloses eukaryotic cells overexpressing eIF4A, eIF4G, eIF4E, PAB1 and RLI1, the overexpression of these genes is but one of a highly variant genus of “modifications” to a eukaryotic cell that results in the increased expression of the desired genes. The breadth of the claims encompass any modification to a host cell including modification of any factor that controls the expression of said genes.13. The scope of enablement rejection of claims 1-6, 8-13, and 20 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, is maintained for the reasons of record and the reasons set forth below. The rejection has been modified in order to address applicants’ amendment to the claims and to incorporate new claims 24-32. Claims 1-6, 8-13, 20 and 24-32 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 eukaryotic cells overexpressing eIF4A, eIF4G, eIF4E, PAB1 and RLI1, does not reasonably provide enablement for all genetic modifications to increase expression of TIF genes as encompassed by the claims. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims. “The test of enablement is not whether any experimentation is necessary, but whether, if experimentation is necessary, it is undue.” In re Angstadt, 537 F.2d 498, 504, 190 USPQ 214, 219 (CCPA 1976). Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands (858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)) as follows: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. See MPEP § 2164.01(a). The Factors considered to be most relevant to the instant rejection are addressed in detail below. (A) The breadth of the claims: As amended, claims 1-6, 8-13, and 24-32 are drawn to a recombinant eukaryotic host cell comprising a heterologous expression cassette expressing a gene of interest (GOI), which host cell is engineered by one or more genetic modifications to increase expression of two or more genes encoding transition initiation factors (TIF genes) of the messenger ribonucleoprotein (mRNP), compared to the host cell prior to the one or more genetic modifications, wherein the TIF genes comprise at least a gene encoding eIF4A and a gene encoding eIF4G, and wherein expression of at least one of the TIF genes is under transcriptional control of a promoter different from the promoter controlling expression of the GOI. As amended, claim 20 is drawn to a polypeptide expression system comprising one or more heterologous expression cassettes expressing two or more TIF genes of the messenger ribnucleoprotein, wherein the TIF genes comprise at least one gene encoding eIF4A and a gene encoding eIF4G, and wherein the polypeptide expression system is a recombinant eukaryotic host cell comprising a heterologous expression cassette comprising a gene of interest (GOI) encoding a protein of interest (POI) with and one or more expression control sequences operably linked to the GOI. C) The state of the prior art; (D) The level of one of ordinary skill; and (E) The level of predictability in the art: As noted above, the scope of the genetic modifications that result in increased expression of TIF genes is unlimited. According to MPEP 2164.03, “…what is known in the art provides evidence as to the question of predictability” and “[I]f one skilled in the art cannot readily anticipate the effect of a change within the subject matter to which that claimed invention pertains, then there is lack of predictability in the art.” The overexpression of PAB1 in a genetically modified yeast was known in the art as taught by Qi et al. (WO 2019/173204 A1; cited on IDS filed on 03/16/2023). The overexpression of a fusion of PAB1 and eIF4G to increase expression of a gene of interest was known in the art as taught by Guo et al. (EP 3663319; cited on IDS filed on 03/16/2023). (F) The amount of direction provided by the inventor and (G) The existence of working examples: The specification discloses the following working examples of increase expression of genes encoding TIF, i.e. eukaryotic cells overexpressing eIF4A, eIF4G, eIF4E, PAB1 and RLI1. Other than these working examples, the specification fails to disclose any other working examples of genetic modifications that result in the increase expression of TIF genes. Moreover, the specification fails to provide guidance regarding modifications to said agents and loci that maintain the desired activity. In view of the overly broad scope of the claims, the lack of guidance and working examples provided in the specification, the high level of unpredictability, and the state of the prior art, undue experimentation would be necessary for a skilled artisan to make and use the entire scope of the claimed invention. Applicants have not provided sufficient guidance to enable one of ordinary skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claims. The scope of the claims must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1970)). Without sufficient guidance, determination of having the desired biological characteristics is unpredictable and the experimentation left to those skilled in the art is unnecessarily, and improperly, extensive and undue. See In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988). RESPONSE TO REMARKS: Beginning on p. 13 of applicants’ remarks, applicants in summary contend that the specification provides the identification and modification of multiple regulatory regions and such modifications are well known to those skilled in the art. This argument is found to be not persuasive because while applicants point to a generic disclosure of regulatory elements that result in overexpression of the TIF genes, such modification are only among a list of many possible combinations of modifications that can result in the claimed increased expression of two or more genes encoding TIF genes. The amount of experimentation needed to make and test each possible modification as encompassed by the claims would be unnecessarily undue. Claim Rejections - 35 USC § 101 14. The rejection of claims 1-6, 8-13, and 22-23 under 35 U.S.C. 101 because the claimed invention is directed to a nature based product without significantly more is withdrawn in view of applicants’ amendment to the claims to recite “comprising a heterologous expression cassette”, which transform the recombinant eukaryotic cell into something that is markedly different in structure than its natural counterpart. Claim Rejections - 35 USC § 102 15. The rejection of claims 20-21 under 35 U.S.C. 102(a)(1) as being anticipated by Guo et al. (WO 2019/024379 A1, 02/07/2019; cited on PTO-892 mailed on 05/14/2026 with US Patent Application Publication 2021189449 as translation) is withdrawn in view of applicants’ amendment to the claims to recite “wherein the TIG genes comprise at least a gene encoding eIF4A and a gene encoding eIF4G”. Claim Rejections - 35 USC § 103 16. The rejection of claims 2 and 22 under 35 U.S.C. 103 as being unpatentable over Guo et al. (WO 2019/024379 A1, 02/07/2019; cited on PTO-892 mailed on 05/14/2026 with US Patent Application Publication 2021189449 as translation) in view of Qi et al. (WO 2019/173204 A1; cited on IDS filed on 03/16/2023) and Li et al. (The Journal of Biological Chemistry, 2001; cited on PTO-892 mailed on 05/14/2026) is withdrawn in view of applicants’ amendment to claim 2 to recite “comprises at least 85% sequence identity to the full length sequence of…” and to cancel claim 22. 17. The rejection of claims 4 and 22 under 35 U.S.C. 103 as being unpatentable over Guo et al. (WO 2019/024379 A1, 02/07/2019; cited on PTO-892 mailed on 05/14/2026 with US Patent Application Publication 2021189449 as translation) in view of Qi et al. (WO 2019/173204 A1; cited on IDS filed on 03/16/2023) and Li et al. (The Journal of Biological Chemistry, 2001; cited on PTO-892 mailed on 05/14/2026) as applied to claims 1-3, 5-6, 8-13, and 22 above and further in view of Rhoads et al. (US Patent 5646009, 1997; cited on IDS filed on 09/21/2023) and Chen et al. (The Journal of Biological Chemistry, 2006; cited on PTO-892 mailed on 05/14/2026) is withdrawn in view of applicants’ amendment to the claims to recite “comprises at least 85% sequence identity to the full length sequence of…” and to cancel claim 22. 18. The rejection of claims 1, 3, 5-6, and 8-13 under 35 U.S.C. 103 as being unpatentable over Guo et al. (WO 2019/024379 A1, 02/07/2019; cited on PTO-892 mailed on 05/14/2026 with US Patent Application Publication 2021189449 as translation) in view of Qi et al. (WO 2019/173204 A1; cited on IDS filed on 03/16/2023) and Li et al. (The Journal of Biological Chemistry, 2001; cited on PTO-892 mailed on 05/14/2026) is maintained for the reasons of record and the reasons set forth below. The rejection has been modified in order to address applicants’ amendment to the claims and in order to incorporate claims 20 and 24-26, which is necessitated by applicants’ amendment to the claims. Claims 1, 3, 5-6, 8-13, 20, and 24-26 are rejected under 35 U.S.C. 103 as being unpatentable over Guo et al. (WO 2019/024379 A1, 02/07/2019; cited on PTO-892 mailed on 05/14/2026 with US Patent Application Publication 2021189449 as translation) in view of Qi et al. (WO 2019/173204 A1; cited on IDS filed on 03/16/2023) and Li et al. (The Journal of Biological Chemistry, 2001; cited on PTO-892 mailed on 05/14/2026). 19. With respect to claim 1, Guo et al. teach a eukaryotic host cell comprising a polypeptide expression system comprising one or more heterologous expression cassettes expressing PAB1 and eIF4G and wherein expression of at least one of the TIF genes is under transcriptional control of a promoter different from the promoter controlling expression of the gene of interest [see Abstract; paragraphs 0008-0049; 0175]. With respect to claim 3, Guo et al. teach the host cell wherein said TIF genes further comprising PAB1 [see Abstract; paragraphs 0008-0049]. With respect to claim 6, Guo et al. teach the host cell overexpresses eIF4G and PAB1 [see Abstract; paragraphs 0008-0049]. With respect to claim 8, Guo et al. teach the host cell wherein said genetic modifications comprises substitutions and expression control sequences [see Abstract; paragraphs 0008-0049]. With respect to claim 9, Guo et al. teach the host cell wherein the genetic modifications include an increase in the number of the TIF genes resulting in increasing the level or activity of the TIF genes [see Abstract; paragraphs 0008-0049]. With respect to claim 10, Guo et al. teach the host cell wherein the TIF genes are endogenous or heterologous to the host cell see Abstract; paragraphs 0008-0049; 0185]. With respect to claim 11, Guo et al. teach a polypeptide expression system comprising one or more heterologous expression cassettes expressing PAB1 and eIF4G [see Abstract; paragraphs 0008-0049] and comprising an expression cassette comprising a gene of interest encoding a protein of interest with one or more expression control sequences operably linked to the gene of interest [see Abstract; paragraphs 0008-0049; 0175]. With respect to claim 12, Guo et al. teach the host cell wherein at least one of the TIF expression cassettes comprises a constitutive promoter and the gene of interest comprises an inducible promoter [see Abstract; paragraphs 0008-0049; 0175]. With respect to claim 13, Guo et al. teach the host cell which is a yeast cell such as Kluveromyces and Saccharomyces [see paragraph 0023]. With respect to claim 20, Guo et al. teach a polypeptide expression system comprising one or more heterologous expression cassettes expressing PAB1 and eIF4G with one or more expression control sequences operably linked to the gene of interest [see Abstract; paragraphs 0008-0049; 0175]. With respect to claim 24, Guo et al. teach the host cell wherein the expression control sequence is selected from a promoter [see paragraph 0055]. With respect to claim 25, Guo et al. teach the host cell wherein the one or more genetic modifications comprise the integration of a heterologous polynucleotide or expression cassette into the host cell genome [see paragraph 0046]. With respect to claim 26, Guo et al. teach the host cell wherein the yeast cell is Saccharomyces cerevisiae or Kluyveromyces lactis [see paragraph 0048] However, Guo et al. does not teach the host cell wherein the gene encodes a eIF4A and the TIF genes are optimized for expressing the TIF gene in the host cell. Qi et al. teach modified yeast cells overexpressing PAB1 that have been codon optimized for the yeast [see Abstract; paragraphs 05, 069]. Li et al. teach that mRNA translation in eukaryotic cells involves eIFs that include eIF4G and eIF4A, an RNA helicase and that eIF4G forms a 1:1 stoichiometric ratio with eIF4A to initiate mRNA translation [see Abstract; p. 29111; p. 29114, column 2]. Before the effective filing date of the claimed invention, it would have been obvious for one of ordinary skill in the art to combine the teachings of Guo et al., Qi et al. and Li et al. according to the teachings of Qi et al. and Li et al. to included codon optimized genes encoding TIFs in yeast and include eIF4A in the expression system of Guo et al. because Guo et al. teach the expression of eIF4G and PAB1 for improving the expression of recombinant proteins in yeast. Qi et al. also teach codon optimized expression of PAB1 in yeast and Li et al. teach that eIF4A interacts with eIF4G in a 1:1 stoichiometric ratio to initiate mRNA translation. One of ordinary skill in the art desiring to increase recombinant protein expression in yeast host cells would have had a reasonable expectation of success, a reasonable level of predictability to combine the teachings of Guo et al., Qi et al. and Li et al. because Li et al. acknowledges that eIF4A interacts with eIF4G to initiate mRNA translation. One overexpressing eIF4G would desire to include eIF4A in order to maximize recombinant protein expression and production. 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. 20. Claim 2 is newly rejected under 35 U.S.C. 103 as being unpatentable over Guo et al. (WO 2019/024379 A1, 02/07/2019; cited on PTO-892 mailed on 05/14/2026 with US Patent Application Publication 2021189449 as translation) in view of Qi et al. (WO 2019/173204 A1; cited on IDS filed on 03/16/2023) and Li et al. (The Journal of Biological Chemistry, 2001; cited on PTO-892 mailed on 05/14/2026) as applied to claims 1, 3, 5-6, 8-13, 20, and 24-26 above and further in view of GenBank XP_002492821 (GenBank, 2009; examiner cited) and GenBank XP_002489692 (GenBank, 2009; examiner cited). This new grounds of rejection is necessitated by applicants’ amendment to the claims. 21. The relevant teachings of Guo et al., Qi et al. and Li et al. as applied to claims 1, 3, 5-6, 8-13, 20, and 24-26 are set forth above. With respect to claim 2, Guo et al. teach Pichia pastoris as a host cell for recombinant protein expression [see paragraph 0110]. However, the combination of Guo et al., Qi et al. and Li et al. do not teach the host cell wherein the eIF4A comprises at least 85% sequence identity to the full length sequence of SEQ ID NO: 12 and the eIF4G comprises at least 85% sequence to the full length sequence of SEQ ID NO: 34. GenBank XP_002492821 teach a eIF4A from Komagataella phaffi (synonymous to Pichia pastoris) that has 100% sequence identity to SEQ ID NO: 12 [see alignment attached as APPENDIX A]. GenBank XP_002489692 teach a eIF4G from Komagataella phaffi (synonymous to Pichia pastoris) that has 100% sequence identity to SEQ ID NO: 34 [see alignment attached as APPENDIX A]. Before the effective filing date of the claimed invention, it would have been obvious for one of ordinary skill in the art to combine the teachings of Guo et al., Qi et al., Li et al., GenBank XP_002492821, and GenBank XP_002489692 because the combination of Guo et al., Qi et al. and Li et al. teach the overexpression of eIF4A and eIF4G in a eukaryotic host cells such as Pichia pastoris. GenBank XP_002492821, and GenBank XP_002489692 teach eIF4A and eIF4G from Komagataella phaffi (synonymous to Pichia pastoris). One of ordinary skill in the art using Pichia pastoris as a host cell in the recombinant host cells of Guo et al., Qi et al. and Li et al. would look to the teachings of GenBank XP_002492821, and GenBank XP_002489692 with a reasonable expectation of success and a reasonable level of predictability because GenBank XP_002492821, and GenBank XP_002489692 acknowledges eIF4A and eIF4G from Komagataella phaffi (synonymous to Pichia pastoris). 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. 22. Claims 4 and 32 are newly rejected under 35 U.S.C. 103 as being unpatentable over Guo et al. (WO 2019/024379 A1, 02/07/2019; cited on PTO-892 mailed on 05/14/2026 with US Patent Application Publication 2021189449 as translation) in view of Qi et al. (WO 2019/173204 A1; cited on IDS filed on 03/16/2023) and Li et al. (The Journal of Biological Chemistry, 2001; cited on PTO-892 mailed on 05/14/2026) as applied to claims 1, 3, 5-6, 8-13, 20, and 24-26 above and further in view of Rhoads et al. (US Patent 5646009, 1997; cited on IDS filed on 09/21/2023), Chen et al. (The Journal of Biological Chemistry, 2006; cited on PTO-892 mailed on 05/14/2026), GenBank XP_002492821 (GenBank, 2009; examiner cited), GenBank XP_002489692 (GenBank, 2009; examiner cited), GenBank XP_002493215 (GenBank, 2009; examiner cited), GenBank XP_002490979 (GenBank, 2009; examiner cited), and GenBank XP_002490978 (GenBank, 2009; examiner cited). This new grounds of rejection is necessitated by applicants’ amendment to the claims. 23. The relevant teachings of Guo et al., Qi et al. and Li et al. as applied to claims 1, 3, 5-6, 8-13, 20, and 24-26 are set forth above. With respect to claims 4 and 32, Guo et al. teach Pichia pastoris as a host cell for recombinant protein expression [see paragraph 0110]. Guo et al. teach a eukaryotic host cell comprising a polypeptide expression system comprising one or more heterologous expression cassettes expressing PAB1 and eIF4G and wherein expression of at least one of the TIF genes is under transcriptional control of a promoter different from the promoter controlling expression of the gene of interest [see Abstract; paragraphs 0008-0049; 0175]. However, the combination of Guo et al., Qi et al. and Li et al. do not teach the host cell wherein the eIF4A comprises at least 85% sequence identity to the full length sequence of SEQ ID NO: 12, the eIF4G comprises at least 85% sequence to the full length sequence of SEQ ID NO: 34, the eIF4E comprises at least 85% sequence identity to the full length sequence of SEQ ID NO: 1, the PAB1 comprises at least 85% sequence identity to the full length sequence of SEQ ID NO: 45, and the RLI1 comprises at least 85% sequence identity to the full length sequence of SEQ ID NO: 56. Rhoads et al. teach a hybrid vector system encoding and overexpressing a TIF, eIF4E, for improving recombinant protein expression in eukaryotic cells [see Abstract; columns 4-6]. Chen et al. teach that ABCE1 (synonymous to RLI1) is essential to cell division and interacts with translation initiation factors in the assembly of the pre-initiation complex [see Abstract; p. 7456]. GenBank XP_002492821 teach a eIF4A from Komagataella phaffi (synonymous to Pichia pastoris) that has 100% sequence identity to SEQ ID NO: 12 [see alignment attached as APPENDIX A]. GenBank XP_002489692 teach a eIF4G from Komagataella phaffi (synonymous to Pichia pastoris) that has 100% sequence identity to SEQ ID NO: 34 [see alignment attached as APPENDIX A]. GenBank XP_002493215 teach a eIF4E from Komagataella phaffi (synonymous to Pichia pastoris) that has 100% sequence identity to SEQ ID NO: 1 [see alignment attached as APPENDIX A]. GenBank XP_002490979 teach a PAB1 from Komagataella phaffi (synonymous to Pichia pastoris) that has 100% sequence identity to SEQ ID NO: 45 [see alignment attached as APPENDIX A]. GenBank XP_002490978 teach a RLI1 from Komagataella phaffi (synonymous to Pichia pastoris) that has 100% sequence identity to SEQ ID NO: 56 [see alignment attached as APPENDIX A]. Before the effective filing date of the claimed invention, it would have been obvious for one of ordinary skill in the art to combine the teachings of Guo et al., Qi et al., Li et al., Rhoads et al., Chen et al. GenBank XP_002492821, GenBank XP_002489692, GenBank XP_002493215, GenBank XP_002490979, and GenBank XP_002490978 because the combination of Guo et al., Qi et al. and Li et al. teach the overexpression of TIF genes such as eIF4A, eIF4G, and PAB1 in a eukaryotic host cells such as Pichia pastoris. Rhoads et al. teach a hybrid vector system encoding and overexpressing a TIF, eIF4E, for improving recombinant protein expression in eukaryotic cells. Chen et al. teach that ABCE1 (synonymous to RLI1) is essential to cell division and interacts with translation initiation factors in the assembly of the pre-initiation complex. GenBank XP_002492821, GenBank XP_002489692, GenBank XP_002493215, GenBank XP_002490979, and GenBank XP_002490978 teach eIF4A, eIF4G, eIF4E, PAB1, and RLI1 from Komagataella phaffi (synonymous to Pichia pastoris). One of ordinary skill in the art using Pichia pastoris as a host cell in the recombinant host cells of Guo et al., Qi et al. and Li et al. would look to the teachings of Rhoads et al., Chen et al. GenBank XP_002492821, GenBank XP_002489692, GenBank XP_002493215, GenBank XP_002490979, and GenBank XP_002490978 with a reasonable expectation of success and a reasonable level of predictability because Rhoads et al. acknowledges that overexpression of eIF4E improves recombinant protein production in eukaryotic cells and Chen et al. acknowledges the role that RLI1 plays in the formation of the pre-initiation complex for protein translation. GenBank XP_002492821, GenBank XP_002489692, GenBank XP_002493215, GenBank XP_002490979, and GenBank XP_002490978 acknowledge eIF4A, eIF4G, eIF4E, PAB1, and RLI1 from Komagataella phaffi (synonymous to Pichia pastoris). 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. 24. Claims 27-29 are newly rejected under 35 U.S.C. 103 as being unpatentable over Guo et al. (WO 2019/024379 A1, 02/07/2019; cited on PTO-892 mailed on 05/14/2026 with US Patent Application Publication 2021189449 as translation) in view of Qi et al. (WO 2019/173204 A1; cited on IDS filed on 03/16/2023) and Li et al. (The Journal of Biological Chemistry, 2001; cited on PTO-892 mailed on 05/14/2026) as applied to claims 1, 3, 5-6, 8-13, 20, and 24-26 above and further in view of Gomes et al. (Advances in Animal and Veterinary Sciences, 2016; examiner cited). This new grounds of rejection is necessitated by applicants’ amendment to the claims to add new claims 27-29. 25. The relevant teachings of Guo et al., Qi et al. and Li et al. as applied to claims 1, 3, 5-6, 8-13, 20, and 24-26 are set forth above. With respect to claims 27-29, Guo et al. teach a eukaryotic host cell comprising a polypeptide expression system comprising one or more heterologous expression cassettes expressing PAB1 and eIF4G and wherein expression of at least one of the TIF genes is under transcriptional control of a promoter different from the promoter controlling expression of the gene of interest [see Abstract; paragraphs 0008-0049; 0175]. However, the combination of Guo et al., Qi et al., and Li et al. does not teach the host cells of claims 27-29. Gomes et al. teach that the need for novel expression host platforms increases with the number of gene targets for various industrial productions, and teach suitable host system needs to be selected depending on the purpose [see p. 346, column 1]. Gomes et al. teach the host systems include bacterial/mammalian/insect/yeast/plant expression system [see p. 346, column 2]. Gomes et al. teach that filamentous fungal systems such as Trichoderma reesei have tremendous capability to secrete grams of protein [see p. 349, column 2], insect systems such as Sf-9, Sf-21 and high five are widely used in recombinant protein expression [see p. 350, column 1], and mammalian systems such as CHO and HEK 293 cells are commonly used for heterologous protein expression [see p. 351, column 1]. Before the effective filing date of the claimed invention, it would have been obvious for one of ordinary skill in the art to combine the teachings of Guo et al., Qi et al., Li et al., and Gomes et al. to choose the appropriate expression host cell depending on the recombinant protein desired because the combination of Guo et al., Qi et al., and Li et al. teach Guo et al., Qi et al. and Li et al. teach the overexpression of TIF genes such as eIF4A, eIF4G, and PAB1 in a eukaryotic host cells. Gomes et al. teach that filamentous fungal systems such as Trichoderma reesei have tremendous capability to secrete grams of protein, insect systems such as Sf-9, Sf-21 and high five are widely used in recombinant protein expression, and mammalian systems such as CHO and HEK 293 cells are commonly used for heterologous protein expression. One of ordinary skill in the art would have had a reasonable expectation of success and a reasonable level of predictability to combine the teachings of Guo et al., Qi et al., Li et al., and Gomes et al. because Gomes et al. acknowledge various eukaryotic host cell systems capable of expressing heterologous proteins. 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. 26. Claim 30 is newly rejected under 35 U.S.C. 103 as being unpatentable over Guo et al. (WO 2019/024379 A1, 02/07/2019; cited on PTO-892 mailed on 05/14/2026 with US Patent Application Publication 2021189449 as translation) in view of Qi et al. (WO 2019/173204 A1; cited on IDS filed on 03/16/2023) and Li et al. (The Journal of Biological Chemistry, 2001; cited on PTO-892 mailed on 05/14/2026) as applied to claims 1, 3, 5-6, 8-13, 20, and 24-26 above and further in view of Gomes et al. (Advances in Animal and Veterinary Sciences, 2016; examiner cited) and Coca et al. (Plant Molecular Biology, 2004; examiner cited). This new grounds of rejection is necessitated by applicants’ amendment to the claims to add new claim 30. 27. The relevant teachings of Guo et al., Qi et al. and Li et al. as applied to claims 1, 3, 5-6, 8-13, 20, and 24-26 are set forth above. With respect to claim 30, Guo et al. teach a eukaryotic host cell comprising a polypeptide expression system comprising one or more heterologous expression cassettes expressing PAB1 and eIF4G and wherein expression of at least one of the TIF genes is under transcriptional control of a promoter different from the promoter controlling expression of the gene of interest [see Abstract; paragraphs 0008-0049; 0175]. However, the combination of Guo et al., Qi et al., and Li et al. does not teach the host cells of claim 30 wherein the monocotyledonous plant cell is a maize cell, a rice cell, a wheat cell, or a Seteria cell. Gomes et al. teach that the need for novel expression host platforms increases with the number of gene targets for various industrial productions, and teach suitable host system needs to be selected depending on the purpose [see p. 346, column 1]. Gomes et al. teach the host systems include bacterial/mammalian/insect/yeast/plant expression system [see p. 346, column 2]. Gomes et al. teach that plant cells constitute an optimal system to express heterologous proteins that require complicated post-translational modifications [see p. 351, column 2]. Coca et al. teach recombinant expression of a heterologous protein in a transgenic rice plant [see Abstract]. Before the effective filing date of the claimed invention, it would have been obvious for one of ordinary skill in the art to combine the teachings of Guo et al., Qi et al., Li et al., Gomes et al., and Coca et al. to choose the appropriate expression host cell depending on the recombinant protein desired because the combination of Guo et al., Qi et al., and Li et al. teach Guo et al., Qi et al. and Li et al. teach the overexpression of TIF genes such as eIF4A, eIF4G, and PAB1 in a eukaryotic host cells. Gomes et al. teach that that plant cells constitute an optimal system to express heterologous proteins that require complicated post-translational modifications [see p. 351, column 2]. One of ordinary skill in the art would have had a reasonable expectation of success and a reasonable level of predictability to combine the teachings of Guo et al., Qi et al., Li et al., Gomes et al., and Coca et al. because Gomes et al. acknowledge various eukaryotic host cell systems capable of expressing heterologous proteins and Coca et al. acknowledges that rice can be used to express heterologous proteins. 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. 28. Claim 31 is newly rejected under 35 U.S.C. 103 as being unpatentable over Guo et al. (WO 2019/024379 A1, 02/07/2019; cited on PTO-892 mailed on 05/14/2026 with US Patent Application Publication 2021189449 as translation) in view of Qi et al. (WO 2019/173204 A1; cited on IDS filed on 03/16/2023) and Li et al. (The Journal of Biological Chemistry, 2001; cited on PTO-892 mailed on 05/14/2026) as applied to claims 1, 3, 5-6, 8-13, 20, and 24-26 above and further in view of Gomes et al. (Advances in Animal and Veterinary Sciences, 2016; examiner cited) and Bakker et al. (PNAS, 2006; examiner cited). This new grounds of rejection is necessitated by applicants’ amendment to the claims to add new claim 31. 29. The relevant teachings of Guo et al., Qi et al. and Li et al. as applied to claims 1, 3, 5-6, 8-13, 20, and 24-26 are set forth above. With respect to claim 31, Guo et al. teach a eukaryotic host cell comprising a polypeptide expression system comprising one or more heterologous expression cassettes expressing PAB1 and eIF4G and wherein expression of at least one of the TIF genes is under transcriptional control of a promoter different from the promoter controlling expression of the gene of interest [see Abstract; paragraphs 0008-0049; 0175]. However, the combination of Guo et al., Qi et al., and Li et al. does not teach the host cells of claim 31 wherein the dicotyledonous plant cell is a cassava cell, a potato cell, a soybean cell, a tomato cell, a tobacco cell, an alfalfa cell, a Phsycomitrella patens cell, or an Arabidopsis cell. Gomes et al. teach that the need for novel expression host platforms increases with the number of gene targets for various industrial productions, and teach suitable host system needs to be selected depending on the purpose [see p. 346, column 1]. Gomes et al. teach the host systems include bacterial/mammalian/insect/yeast/plant expression system [see p. 346, column 2]. Gomes et al. teach that plant cells constitute an optimal system to express heterologous proteins that require complicated post-translational modifications [see p. 351, column 2]. Bakker et al. teach heterologous expression of a recombinant protein in a tobacco cell [see Abstract]. Before the effective filing date of the claimed invention, it would have been obvious for one of ordinary skill in the art to combine the teachings of Guo et al., Qi et al., Li et al., Gomes et al., and Coca et al. to choose the appropriate expression host cell depending on the recombinant protein desired because the combination of Guo et al., Qi et al., and Li et al. teach Guo et al., Qi et al. and Li et al. teach the overexpression of TIF genes such as eIF4A, eIF4G, and PAB1 in a eukaryotic host cells. Gomes et al. teach that that plant cells constitute an optimal system to express heterologous proteins that require complicated post-translational modifications [see p. 351, column 2]. One of ordinary skill in the art would have had a reasonable expectation of success and a reasonable level of predictability to combine the teachings of Guo et al., Qi et al., Li et al., Gomes et al., and Coca et al. because Gomes et al. acknowledge various eukaryotic host cell systems capable of expressing heterologous proteins and Bakker et al. acknowledges that tobacco cells can be used to express heterologous proteins. 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 Regarding Prior Art Rejections 29. Beginning on p. 16 of applicants’ remarks, applicants in summary contend that Guo’s teachings relate to in vitro protein synthesis system and fails to teach or suggest that overexpression of a PAB1 element and eIF4G element would improve the yield of a protein when expressed by in vivo expression. These arguments are found to be not persuasive for the reasons of record and the reasons set forth below. It is noted that the features upon which applicant relies (i.e., in vivo protein expression) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). The claim requires a recombinant eukaryotic host cell containing modifications to increase expression of TIF genes and does not require an in vivo system. The teachings of Guo in combination with Qi et al. and Li et al. containing genetic modifications in a eukaryotic cell system reasonably read on the claims. Conclusion 30. Status of the claims: Claims 1-6, 8-20, and 24-32 are pending. Claims 1-6, 8-20, and 24-32 are pending. Claims 14-18 stand withdrawn pursuant to 37 CFR 1.142(b). Claims 1-6, 8-13, 20, and 24-32 are rejected. No claims are in condition for an 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 PAUL J HOLLAND whose telephone number is (571)270-3537. The examiner can normally be reached Monday to Friday from 8AM to 5PM. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached at 571-272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. 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If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /PAUL J HOLLAND/Primary Examiner, Art Unit 1656 APPENDIX A GenBank XP_002492821 with SEQ ID NO: 12 Query Match 100.0%; Score 1998; Length 403; Best Local Similarity 100.0%; Matches 403; Conservative 0; Mismatches 0; Indels 0; Gaps 0; Qy 1 MSEGIIEIDTNLIETNYDQVVSTFDELNLKEQILRAVFAYGYEFPSAIQSRAILPIVAGR 60 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1 MSEGIIEIDTNLIETNYDQVVSTFDELNLKEQILRAVFAYGYEFPSAIQSRAILPIVAGR 60 Qy 61 DVLAQAQSGTGKTATFAISALQRLDEKLKAAQVLILAPTRELALQIKKVVLALGMHLNIS 120 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 61 DVLAQAQSGTGKTATFAISALQRLDEKLKAAQVLILAPTRELALQIKKVVLALGMHLNIS 120 Qy 121 VHACIGGVDPALDVKAFNSGVQIVVGTPGRVQDMIERGAFRTENVKMVILDEADEMLSTG 180 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 121 VHACIGGVDPALDVKAFNSGVQIVVGTPGRVQDMIERGAFRTENVKMVILDEADEMLSTG 180 Qy 181 FKEQIYTLFTLLPSTTQVVLLSATMPQEVLEVTTKFMNNPIRILVKKDQLTLEGIKQFYV 240 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 181 FKEQIYTLFTLLPSTTQVVLLSATMPQEVLEVTTKFMNNPIRILVKKDQLTLEGIKQFYV 240 Qy 241 DVGEEQYKFDCLCDLYDSISVTQAVIFCNTRRKVEELTERLTAQKFTVSAIHSELSQTER 300 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 241 DVGEEQYKFDCLCDLYDSISVTQAVIFCNTRRKVEELTERLTAQKFTVSAIHSELSQTER 300 Qy 301 DTIMQEFRTGSSRILISTDLLARGIDVQQVSLVINYDLPSNKENYIHRIGRGGRFGRKGV 360 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 301 DTIMQEFRTGSSRILISTDLLARGIDVQQVSLVINYDLPSNKENYIHRIGRGGRFGRKGV 360 Qy 361 AINFVTSKDVEMMKEIEKFYSTQIDELPSSITDLFETEEVNES 403 ||||||||||||||||||||||||||||||||||||||||||| Db 361 AINFVTSKDVEMMKEIEKFYSTQIDELPSSITDLFETEEVNES 403 GenBank XP_002489692 with SEQ ID NO: 34 Query Match 100.0%; Score 5683; Length 1098; Best Local Similarity 100.0%; Matches 1098; Conservative 0; Mismatches 0; Indels 0; Gaps 0; Qy 1 MSNKNVDTAPDNGSGGSNSPASVPHYPQQHRANYNPHKNHTNHGGNNGGAQGYMQHQQQQ 60 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1 MSNKNVDTAPDNGSGGSNSPASVPHYPQQHRANYNPHKNHTNHGGNNGGAQGYMQHQQQQ 60 Qy 61 QMYYNQMGYPMPYPNAGGNFNQNVYLVPYNTMVPGTPYGAGAPGVPPSYPVSPSPAFASP 120 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 61 QMYYNQMGYPMPYPNAGGNFNQNVYLVPYNTMVPGTPYGAGAPGVPPSYPVSPSPAFASP 120 Qy 121 QKTHVPVSLRTPSGEPINLVPAGQTSSSSSNASPHVKSTSIPPSAVTSPAASIAPTVASP 180 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 121 QKTHVPVSLRTPSGEPINLVPAGQTSSSSSNASPHVKSTSIPPSAVTSPAASIAPTVASP 180 Qy 181 TKAAAGSEDAGKTRDAFKQMVQALAAKKKAAAAAKAEGKTDDKKESVESKPKSAVQPETK 240 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 181 TKAAAGSEDAGKTRDAFKQMVQALAAKKKAAAAAKAEGKTDDKKESVESKPKSAVQPETK 240 Qy 241 PKVEVKLEPKPKVEVKLEPKPKVEIKLEPKPVSEAKPETKTVPEVEEPSTVATIKSESTP 300 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 241 PKVEVKLEPKPKVEVKLEPKPKVEIKLEPKPVSEAKPETKTVPEVEEPSTVATIKSESTP 300 Qy 301 IEELKPKVEVTPEVASKPEQVESAQEPANDVKPSEVSAKEVQESKEESLKQPKEALNDIK 360 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 301 IEELKPKVEVTPEVASKPEQVESAQEPANDVKPSEVSAKEVQESKEESLKQPKEALNDIK 360 Qy 361 STEESNKKFSLPEEESNDHQTLSQIQGVKDTEQSQEFEEPQGTQETQETQETQETAKPLE 420 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 361 STEESNKKFSLPEEESNDHQTLSQIQGVKDTEQSQEFEEPQGTQETQETQETQETAKPLE 420 Qy 421 AQAPQEIQETQEPEEVQEQTPETSETVSSVTEEVSPAPAPGLPLSKFLDRIRKAPAISNP 480 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 421 AQAPQEIQETQEPEEVQEQTPETSETVSSVTEEVSPAPAPGLPLSKFLDRIRKAPAISNP 480 Qy 481 FKHEYSGDFHGPDESLSGLKTIKYDPGFLIQFATFNFHIDEDFINDVGSKVVIPVNTRRD 540 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 481 FKHEYSGDFHGPDESLSGLKTIKYDPGFLIQFATFNFHIDEDFINDVGSKVVIPVNTRRD 540 Qy 541 NFSKSMSTSNFKGSGRNMGSNFRNDFGSRNNSKQGSKKKNKSQKSQSRRGPKYSNEEEPA 600 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 541 NFSKSMSTSNFKGSGRNMGSNFRNDFGSRNNSKQGSKKKNKSQKSQSRRGPKYSNEEEPA 600 Qy 601 EPAVPAELPNRAASKWVPRSLRNKEAEVKTAPDGSIIVSEEDIKRKTKSLLNKLTLEFFD 660 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 601 EPAVPAELPNRAASKWVPRSLRNKEAEVKTAPDGSIIVSEEDIKRKTKSLLNKLTLEFFD 660 Qy 661 DISNDIIALTKQAQWEDDVKTLKQVIESIFAKACDEPYWSSMYAKLCAKMCKDTPPEIKE 720 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 661 DISNDIIALTKQAQWEDDVKTLKQVIESIFAKACDEPYWSSMYAKLCAKMCKDTPPEIKE 720 Qy 721 TNEKGNTFTGGDLVRRVLINRCQTEYQKGWIDQLPTNEDGSPLEPELMSDEYYKQAAAKR 780 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 721 TNEKGNTFTGGDLVRRVLINRCQTEYQKGWIDQLPTNEDGSPLEPELMSDEYYKQAAAKR 780 Qy 781 RGLGLVKFIGQLYQLNLLSDNVIFHCVLGQSKETDNPSEDTMENLVQLLEAVGYRMEMSS 840 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 781 RGLGLVKFIGQLYQLNLLSDNVIFHCVLGQSKETDNPSEDTMENLVQLLEAVGYRMEMSS 840 Qy 841 EPKIRRVLDLAFANIKAIVDANKIPSRIRFMLMDLMDLRRNGWATTEENAGPKTIQEIHL 900 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 841 EPKIRRVLDLAFANIKAIVDANKIPSRIRFMLMDLMDLRRNGWATTEENAGPKTIQEIHL 900 Qy 901 EAEIKRSEEEREKERDRHSRRGRYNDSKPNSRQKSSWGSSVVSPNDIRNAGYVRNSDKSL 960 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 901 EAEIKRSEEEREKERDRHSRRGRYNDSKPNSRQKSSWGSSVVSPNDIRNAGYVRNSDKSL 960 Qy 961 GPVNSFSRGKSSRQASKQSNSDFTSVPITSSGSRTALNHSGDSSTSLNEPQSREYSKKSE 1020 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 961 GPVNSFSRGKSSRQASKQSNSDFTSVPITSSGSRTALNHSGDSSTSLNEPQSREYSKKSE 1020 Qy 1021 SRPAPSNIFAALEDHDHDHEHGHEQEENKHSKDLQNGEAEAPEDDNVGEIAQADENVQGQ 1080 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1021 SRPAPSNIFAALEDHDHDHEHGHEQEENKHSKDLQNGEAEAPEDDNVGEIAQADENVQGQ 1080 Qy 1081 EQEEEREEEREQEEEQEV 1098 |||||||||||||||||| Db 1081 EQEEEREEEREQEEEQEV 1098 GenBank XP_002493215 with SEQ ID NO: 1 Query Match 100.0%; Score 1069; Length 202; Best Local Similarity 100.0%; Matches 202; Conservative 0; Mismatches 0; Indels 0; Gaps 0; Qy 1 MSETENAPHEKSLLDDQVDFTVKHPLNSEWTLWYTKPAVHEQESWSDLLRPIISFNSVEE 60 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1 MSETENAPHEKSLLDDQVDFTVKHPLNSEWTLWYTKPAVHEQESWSDLLRPIISFNSVEE 60 Qy 61 FWGIFNSIPKASDLPVKSDYHLFRDGIKPEWEDERNANGGKLTYQFAYRKVDINELWSRG 120 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 61 FWGIFNSIPKASDLPVKSDYHLFRDGIKPEWEDERNANGGKLTYQFAYRKVDINELWSRG 120 Qy 121 LLSVIGETIQDDDGETEVNGIVLSIRRAALKIALWTKSKDEAVLRPIGERFKKVLKLTAR 180 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 121 LLSVIGETIQDDDGETEVNGIVLSIRRAALKIALWTKSKDEAVLRPIGERFKKVLKLTAR 180 Qy 181 DHIDFQPHKSGAGSKNVPSFSI 202 |||||||||||||||||||||| Db 181 DHIDFQPHKSGAGSKNVPSFSI 202 GenBank XP_002490979 with SEQ ID NO: 45 Query Match 100.0%; Score 3239; Length 626; Best Local Similarity 100.0%; Matches 626; Conservative 0; Mismatches 0; Indels 0; Gaps 0; Qy 1 MSVDTKEVQESLDQLNISESPATAVTEETPATSTEAAEESNESSTQASETLASLYVGELD 60 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1 MSVDTKEVQESLDQLNISESPATAVTEETPATSTEAAEESNESSTQASETLASLYVGELD 60 Qy 61 PTVTESDLYEFFSPIGSVNSIRVCRDAVTKRSLGYGYVNFHSQAAGERALEELNYAEIKG 120 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 61 PTVTESDLYEFFSPIGSVNSIRVCRDAVTKRSLGYGYVNFHSQAAGERALEELNYAEIKG 120 Qy 121 VRCRLMWSQRDPSLRRSGSGNIFIKNLDPAIENKTLHDTFSSFGKVLSCKVATDENGNSK 180 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 121 VRCRLMWSQRDPSLRRSGSGNIFIKNLDPAIENKTLHDTFSSFGKVLSCKVATDENGNSK 180 Qy 181 GFGFVHYESDEAAQAAIENINGMLLNGREIYVGPHLAKKDRESRFQEMIKNYTNVFVKNF 240 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 181 GFGFVHYESDEAAQAAIENINGMLLNGREIYVGPHLAKKDRESRFQEMIKNYTNVFVKNF 240 Qy 241 DTESTEDELRELFESYGPITSIHLQVDSEGHNKGFGFVNFAEHDDAVKAVEALNDKEYKG 300 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 241 DTESTEDELRELFESYGPITSIHLQVDSEGHNKGFGFVNFAEHDDAVKAVEALNDKEYKG 300 Qy 301 KPLYVGRAQKKNERVHELTKKYEADRLEKLQKYQSVNLFIKNLDESIDDARLEEEFKPFG 360 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 301 KPLYVGRAQKKNERVHELTKKYEADRLEKLQKYQSVNLFIKNLDESIDDARLEEEFKPFG 360 Qy 361 TITSAKVMLDENGKSRGFGFVCLSTPEEATKAISEMNQRMVANKPLYVALAQPKAIRRSQ 420 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 361 TITSAKVMLDENGKSRGFGFVCLSTPEEATKAISEMNQRMVANKPLYVALAQPKAIRRSQ 420 Qy 421 LAQQIQARNQMRMQQQAGPGIPNQFVQPIFYGQQPGMLPPGARVPPMGNQIPQFAGMPRP 480 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 421 LAQQIQARNQMRMQQQAGPGIPNQFVQPIFYGQQPGMLPPGARVPPMGNQIPQFAGMPRP 480 Qy 481 GPFPQGQFPRMAPNGQPMPVYGQPVFNGNGPQQRGYYPNNRQNKNRNQKEEGNSLAAILP 540 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 481 GPFPQGQFPRMAPNGQPMPVYGQPVFNGNGPQQRGYYPNNRQNKNRNQKEEGNSLAAILP 540 Qy 541 QLPLEQQKRVLGEELYPKVVATNKTQDPEAAGKITGMILDLDNQEILQLLEDEELFNTHF 600 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 541 QLPLEQQKRVLGEELYPKVVATNKTQDPEAAGKITGMILDLDNQEILQLLEDEELFNTHF 600 Qy 601 NEALQAYEEYKSKTVEQQQQADAQAN 626 |||||||||||||||||||||||||| Db 601 NEALQAYEEYKSKTVEQQQQADAQAN 626 GenBank XP_002490978 with SEQ ID NO: 56 Query Match 100.0%; Score 3122; Length 606; Best Local Similarity 100.0%; Matches 606; Conservative 0; Mismatches 0; Indels 0; Gaps 0; Qy 1 MSEKNTRIAIVSDDRCKPKKCRQECRKSCPVVKTGKLCIEVEAYSKIAFISETLCIGCGI 60 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1 MSEKNTRIAIVSDDRCKPKKCRQECRKSCPVVKTGKLCIEVEAYSKIAFISETLCIGCGI 60 Qy 61 CVKKCPFGAINIINLPTNLEKEVTHRYSANSFKLHRLPTPRPGQVLGLVGTNGIGKSTAL 120 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 61 CVKKCPFGAINIINLPTNLEKEVTHRYSANSFKLHRLPTPRPGQVLGLVGTNGIGKSTAL 120 Qy 121 KILAGKQKPNLGRYDAPPDWEEILKYFRGSELQNYFTKVLEDNIKAIIKPQYVDNLPRAI 180 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 121 KILAGKQKPNLGRYDAPPDWEEILKYFRGSELQNYFTKVLEDNIKAIIKPQYVDNLPRAI 180 Qy 181 KGPVNKVGELLKAKLERKEEGKHIIQVLELKHVLNREVAKLSGGELQRFAIGMTCVQDAN 240 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 181 KGPVNKVGELLKAKLERKEEGKHIIQVLELKHVLNREVAKLSGGELQRFAIGMTCVQDAN 240 Qy 241 VYMFDEPSSYLDVKQRLNAAQIIRSLLHATCYVIVVEHDLSVLDYLSDFVCILYGVPSVY 300 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 241 VYMFDEPSSYLDVKQRLNAAQIIRSLLHATCYVIVVEHDLSVLDYLSDFVCILYGVPSVY 300 Qy 301 GVVTLPASVREGINIFLDGHIPTENLRFRTESLKFKLTDASDSVLIEQSRAFEYPKMVKT 360 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 301 GVVTLPASVREGINIFLDGHIPTENLRFRTESLKFKLTDASDSVLIEQSRAFEYPKMVKT 360 Qy 361 QGDFKLTVNAGDFSDSEIIVMMGENGTGKTTLCKLLAGAIEGDEGTKVPKLNVSMKPQKI 420 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 361 QGDFKLTVNAGDFSDSEIIVMMGENGTGKTTLCKLLAGAIEGDEGTKVPKLNVSMKPQKI 420 Qy 421 APKFTGTVRQLFLKKIRSSFLHPQFNTDVMKPLKVDDVIDQEVQHLSGGELQRVAIVLAL 480 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 421 APKFTGTVRQLFLKKIRSSFLHPQFNTDVMKPLKVDDVIDQEVQHLSGGELQRVAIVLAL 480 Qy 481 GKEADIYLIDEPSAYLDSEQRIICSKVIRRFILHSKKTAFIVEHDFIMATYLADKVMVFE 540 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 481 GKEADIYLIDEPSAYLDSEQRIICSKVIRRFILHSKKTAFIVEHDFIMATYLADKVMVFE 540 Qy 541 GQPSKNAVANRPETLLTGCNRFLKNLNVTFRRDPNSFRPRINKLDSQMDREQKLSGNYFF 600 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 541 GQPSKNAVANRPETLLTGCNRFLKNLNVTFRRDPNSFRPRINKLDSQMDREQKLSGNYFF 600 Qy 601 LENTEL 606 |||||| Db 601 LENTEL 606