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 .
DETAILED ACTION
This application is a 371 of PCT/FR2020/052282.
The response filed on May 6, 2026 has been entered.
Election/Restrictions
Applicant elected with traverse of Group I with a species election of SEQ ID NO:2 as the ID78713 gene encoding SEQ ID NO:3 in the reply filed on January 23, 2025.
Claims 25-31 and 34 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on January 23, 2025.
Status of Claims
Claims 17-19, 25-31, and 33-40 are pending.
Claims 25-31 and 34 are withdrawn.
Claims 17-19, 33, and 35-40 are under examination.
Response to Arguments
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 17-19, 33, and 35-40 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bodie (US 9,587,242 – form PTO-892), GL985066 (GenBank Database. July 25, 2016 – form PTO-892), and G0RL27_HYPJQ (UniPRotKB/TrEMBL Datablase. June 7, 2017 – form PTO-892),
MPEP 2111.01 states that ''[d]uring examination, the claims must be interpreted as broadly as their terms reasonably allow.'' MPEP 2113 states that “ [P]product by process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps. [E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production.”. In the instant case, the structure of the claimed Trichoderma reesei implied is the same whether the Trichoderma reesei is obtained from use of the invalidation cassette comprising a nucleotide sequence of SEQ ID NO:1 or is obtained from mutagenesis, as long as the resulting product has the structural limitations recited in the claim, a Trichoderma reesei, wherein the ID78713 gene of SEQ ID NO:2 has been invalidated. Therefore, the claims encompass a Trichoderma reesei comprising an invalidated ID78713 gene, wherein the ID78713 gene comprises the nucleotide sequence of SEQ ID NO:2 and encodes a protein having the amino acid sequence of SEQ ID NO:3.
Regarding claim 17, Bodie discloses a genetically modified fungus, Trichoderma reesei, wherein its Gas 1/Gel 1 gene encoding β-(1,3)-glucanosyltransferase of SEQ ID NO:1 has been invalidated (claims 1-2, Column 2, lines 14-21 and lines 43-50, Column 12 line 45 through Column 14, and Example 1).
Regarding claim 18, the genetically modified Trichoderma reesei of Bodie has a reduced viscosity compared to the Trichoderma reesei not comprising the invalidated Gas 1/Gel 1 gene (Column 1, lines 58-60, Column 8, lines 41-51, Column 11, lines 25-36, and Column 24 lines 36-57). Bodie discloses that filamentous fungi are well-suited for large scale production of enzymes and other protein for industrial, pharmaceutical, animal health and food and beverage application (Column 1, lines 34-44). Bodie discloses that filamentous fungi having reduced viscosity has an advantageous in large-scale production of enzymes or proteins because the higher the viscosity of the broth, the less uniform the distribution of oxygen and nutrients, and the more energy required to agitate the culture and the viscosity of the broth becomes sufficiently high to significantly interfere with the dissolution of oxygen and nutrients, thereby adversely affecting the growth of the fungi (Column 1, lines 45-54).
Regarding claims 19 and 33, the Gas 1/Gel 1 gene has been inactivated by mutagenesis in the genetically modified Trichoderma reesei of Bodie (claim 5 and Column 2, lines 14-26).
Bodie does not disclose a Trichoderma reesei comprising an invalidated gene having the nucleic acid sequence of SEQ ID NO:2 and encoding a protein having the amino acid sequence of SEQ ID NO:3.
Regarding claims 17 and 35-40, G0RL27_HYPJQ discloses a Trichoderma reesei β-(1,3)-glucanosyltransferase (ORF Name TRIREDRAFT_78713) having 100% sequence identity to SEQ ID NO:3 of the instant application (see page 2 and the sequence alignment below). Said β-(1,3)-glucanosyltransferase is encoded by a gene having the accession number GL985066. GL985066 discloses a gene having 100% sequence identity to the ID78713 gene of SEQ ID NO:2 of the instant application (see page 3 and the sequence alignment below).
Therefore, in combining the above references, it would have been obvious to one having ordinary skill in the art before the time the claimed invention was effectively filed to substitute the invalidation of the Trichoderma reesei Gas-1/Gel-1 gene encoding a β-(1,3)-glucanosyltransferase (SEQ ID NO:1) of Bodie with another Trichoderma reesei β-(1,3)-glucanosyltransferase gene. The rationale to support a conclusion that the claims would have been obvious is that the substitution of one known element (invalidation of a β-(1,3)-glucanosyltransferase in a filamentous fungi) for another yields predictable results to one of ordinary skill in the art. One having ordinary skill in the art would have been motivated to do so in order to further reduce viscosity in Trichoderma reesei. One of ordinary skill in the art would have had a reasonable expectation of success since Bodie teaches invalidating genes encoding β-(1,3)-glucanosyltransferase in Trichoderma reesei to reduce is viscosity thereby improving large-scale production of enzymes and proteins, G0RL27_HYPJQ teaches a Trichoderma reesei β-(1,3)-glucanosyltransferase, and GL985066 teaches a gene encoding said Trichoderma reesei β-(1,3)-glucanosyltransferase of G0RL27_HYPJQ.
Therefore, the above references render claims 17-19, 33, and 35-40 prima facie obvious.
Applicant's arguments filed May 6, 2026 have been fully considered but they are not persuasive.
Applicant summarizes the teachings of the cited references as: Bodie refers to a strain of Trichoderma reesei wherein the gene gas1 is invalidated and this strain 77B7Δgas1 has a reduction in broth viscosity compared to the parent Morph 77B7 (see column 24 of Bodie, emphasis added). GL985066 and GORL27_HYPJQ describe the protein and gene of SEQ ID NO:3 and SEQ ID NO:2 of the present invention.
Applicant argues that the divulgation of these sequences does not presuppose the effect of their invalidation since GL985066 and GORL27_HYPJQ simply refer to sequences in a database. Applicant argues that there is no disclosure, nor incentive, that the invalidation of the gene of SEQ ID NO:2 would achieve a reduced-viscosity phenotype. Applicant argues that there is no characteristic in the documents GL985066 and GORL27_HYPJQ suggesting that the invalidation of the gene of SEQ ID NO:2 or a gene encoding a protein of SEQ ID NO:3 would produce a morphology change in Trichoderma reesei that results in a reduced viscosity phenotype.
This is not found persuasive.
MPEP 2143.02. I. states that "[c]onclusive proof of efficacy is not required to show a reasonable expectation of success." There is no requirement that a prior art reference teach working examples, experiments, and results to support a prima facie case of obviousness”. MPEP 2144.I. states that the “rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law.”. In the instant case, with the disclosure of Bodie at hand, one of ordinary skill in the art would have recognized to invalidate genes encoding a β-(1,3)-glucanosyltransferase in T. reesei other than those expressly disclosed by Bodie. One having ordinary skill in the art would have been motivated to do so in order to further reduce viscosity in Trichoderma reesei. Further, MPEP 2143.02. II. states that “[o]bviousness does not require absolute predictability, but at least some degree of predictability is required.”. In the instant case, one of ordinary skill in the art would have had a reasonable expectation of success since Bodie teaches invalidating genes encoding β-(1,3)-glucanosyltransferase in Trichoderma reesei to reduce is viscosity thereby improving large-scale production of enzymes and proteins, G0RL27_HYPJQ teaches a Trichoderma reesei β-(1,3)-glucanosyltransferase, and GL985066 teaches a gene encoding said Trichoderma reesei β-(1,3)-glucanosyltransferase of G0RL27_HYPJQ.
Applicant argues that the claims are not obvious according to MPEP 2143.I.B. because (1) the Bodie reference was identified by the Examiner but Bodie does not disclose a Trichoderma reesei wherein the gene of SEQ ID NO:2 nor a gene encoding a protein of SEQ ID NO:3 was invalidated, (2) Examiner cited the documents GL985066 and GORL27_HYPJQ to argue the gene of SEQ ID NO:2 or a gene encoding a protein of SEQ ID NO:3 was known but at the time the present invention was made, it was not known that the invalidation of the gene of SEQ ID NO:2 or a gene encoding a protein of SEQ ID NO:3 would produce a morphology change in Trichoderma reesei that results in a reduced viscosity phenotype. The function of the gene of SEQ ID NO:2
or of the gene encoding a protein of SEQ ID NO:3 was not known, contrary to what is required by the applicable exam guidelines cited in the MPEP. It is correct that gas1 and gel3 share the same enzymatic reaction (i.e. β-(1,3)-glucanosyltransferase). However, this does not mean the biological function of gas1 and gel3 are the same. The function of the substituted component (here gel3) was not known, and the cited documents do not mention, nor render obvious that gas1 and gel3 share the same biological function; and (3) Examiner considers the results of the substitution would have been
predictable because gas1 and gel3 refers both to ß-(1,3)-glucanosyltransferase. For the reasons explained above for the paragraph (2), the same enzymatic reaction (i.e. ß-(1,3)- glucanosyltransferase) does not mean the biological function of gas1 and gel3 are the same. Therefore, without experimental evidence or further information on the biological function of gas1 and gel3, it cannot be considered that the substitution of the invalidation of gas1 gene by the invalidation of gel3 gene is predictable.
This is not found persuasive.
According to MPEP 2143.I.B.(1), Bodie discloses a device (Trichoderma reesei, wherein its Gas 1/Gel 1 gene encoding β-(1,3)-glucanosyltransferase has been eliminated) which is different from the claimed device by the substitution of some components (invalidated β-(1,3)-glucanosyltransferase) with other components. There is no requirement that the prior art (Bodie) disclose a Trichoderma reesei wherein the gene of SEQ ID NO:2 nor a gene encoding a protein of SEQ ID NO:3 was invalidated.
According to MPEP 2143.I.B.(2), G0RL27_HYPJQ and GL985066 disclose the substituted component (Trichoderma reesei β-(1,3)-glucanosyltransferase having 100% sequence identity to SEQ ID NO:3 and a gene having 100% sequence identity to the ID78713 gene of SEQ ID NO:2 of the instant application) and its function (β-(1,3)-glucanosyltransferase) was known in the art. Since (i) each of the claimed elements is found within the scope and content of the prior art (Bodie, G0RL27_HYPJQ and GL985066), (ii) one of ordinary skill in the art could have combined the elements as claimed by methods known at the time the invention was made (disclosed by Bodie); and (iii) one of ordinary skill in the art would have recognized at the time the invention was made that the capabilities or functions of the combination were predictable. MPEP 2143.02. II. states that “[o]bviousness does not require absolute predictability, but at least some degree of predictability is required.”. In the instant case, one of ordinary skill in the art would have had a reasonable expectation of success since Bodie teaches invalidating genes encoding β-(1,3)-glucanosyltransferase in Trichoderma reesei to reduce is viscosity thereby improving large-scale production of enzymes and proteins, G0RL27_HYPJQ teaches a Trichoderma reesei β-(1,3)-glucanosyltransferase, and GL985066 teaches a gene encoding said Trichoderma reesei β-(1,3)-glucanosyltransferase of G0RL27_HYPJQ.
According to MPEP 2143.I.B.(3), “[o]bviousness does not require absolute predictability, but at least some degree of predictability is required.”. In the instant case, one of ordinary skill in the art could have substituted one known element for another, and the results of the substitution would have been predictable because Bodie teaches invalidating genes encoding β-(1,3)-glucanosyltransferase in Trichoderma reesei to reduce is viscosity thereby improving large-scale production of enzymes and proteins, G0RL27_HYPJQ teaches a Trichoderma reesei β-(1,3)-glucanosyltransferase, and GL985066 teaches a gene encoding said Trichoderma reesei β-(1,3)-glucanosyltransferase of G0RL27_HYPJQ.
Therefore, the rejection has been maintained.
Conclusion
Claims 17-19, 25-31, and 33-40 are pending.
Claims 25-31 and 34 are withdrawn.
Claims 17-19, 33, and 35-40 are rejected.
THIS ACTION IS MADE FINAL. 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 YONG D PAK whose telephone number is (571)272-0935. The examiner can normally be reached M-Th: 5:30 am - 3:30 pm.
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, Robert Mondesi can be reached on 408-918-7584. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/YONG D PAK/Primary Examiner, Art Unit 1652
Sequence alignment of SEQ ID NO:3 of the instant application (“Qy”) and Trichoderma reesei β-(1,3)-glucanosyltransferase of G0RL27_HYPJQ (“Db”)
G0RL27_HYPJQ
ID G0RL27_HYPJQ Unreviewed; 374 AA.
AC G0RL27;
DT 19-OCT-2011, integrated into UniProtKB/TrEMBL.
DT 19-OCT-2011, sequence version 1.
DT 27-NOV-2024, entry version 42.
DE RecName: Full=1,3-beta-glucanosyltransferase {ECO:0000256|RuleBase:RU361209};
DE EC=2.4.1.- {ECO:0000256|RuleBase:RU361209};
DE Flags: Fragment;
GN ORFNames=TRIREDRAFT_78713 {ECO:0000313|EMBL:EGR48094.1};
OS Hypocrea jecorina (strain QM6a) (Trichoderma reesei).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Hypocreaceae; Trichoderma.
OX NCBI_TaxID=431241 {ECO:0000313|Proteomes:UP000008984};
RN [1] {ECO:0000313|EMBL:EGR48094.1, ECO:0000313|Proteomes:UP000008984}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=QM6a {ECO:0000313|EMBL:EGR48094.1,
RC ECO:0000313|Proteomes:UP000008984};
RX PubMed=18454138; DOI=10.1038/nbt1403;
RA Martinez D., Berka R.M., Henrissat B., Saloheimo M., Arvas M., Baker S.E.,
RA Chapman J., Chertkov O., Coutinho P.M., Cullen D., Danchin E.G.,
RA Grigoriev I.V., Harris P., Jackson M., Kubicek C.P., Han C.S., Ho I.,
RA Larrondo L.F., de Leon A.L., Magnuson J.K., Merino S., Misra M., Nelson B.,
RA Putnam N., Robbertse B., Salamov A.A., Schmoll M., Terry A., Thayer N.,
RA Westerholm-Parvinen A., Schoch C.L., Yao J., Barabote R., Nelson M.A.,
RA Detter C., Bruce D., Kuske C.R., Xie G., Richardson P., Rokhsar D.S.,
RA Lucas S.M., Rubin E.M., Dunn-Coleman N., Ward M., Brettin T.S.;
RT "Genome sequencing and analysis of the biomass-degrading fungus Trichoderma
RT reesei (syn. Hypocrea jecorina).";
RL Nat. Biotechnol. 26:553-560(2008).
CC -!- FUNCTION: Splits internally a 1,3-beta-glucan molecule and transfers
CC the newly generated reducing end (the donor) to the non-reducing end of
CC another 1,3-beta-glucan molecule (the acceptor) forming a 1,3-beta
CC linkage, resulting in the elongation of 1,3-beta-glucan chains in the
CC cell wall. {ECO:0000256|RuleBase:RU361209}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000256|ARBA:ARBA00004609,
CC ECO:0000256|RuleBase:RU361209}; Lipid-anchor, GPI-anchor
CC {ECO:0000256|ARBA:ARBA00004609, ECO:0000256|RuleBase:RU361209}.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 72 family.
CC {ECO:0000256|ARBA:ARBA00007528, ECO:0000256|RuleBase:RU361209}.
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DR EMBL; GL985066; EGR48094.1; -; Genomic_DNA.
DR RefSeq; XP_006966138.1; XM_006966076.1.
DR AlphaFoldDB; G0RL27; -.
DR EnsemblFungi; EGR48094; EGR48094; TRIREDRAFT_78713.
DR GeneID; 18488920; -.
DR KEGG; tre:TRIREDRAFT_78713; -.
DR VEuPathDB; FungiDB:TRIREDRAFT_78713; -.
DR eggNOG; ENOG502SHAA; Eukaryota.
DR HOGENOM; CLU_021855_0_0_1; -.
DR OrthoDB; 2783940at2759; -.
DR Proteomes; UP000008984; Unassembled WGS sequence.
DR GO; GO:0043188; C:cell septum edging; IEA:EnsemblFungi.
DR GO; GO:0051286; C:cell tip; IEA:EnsemblFungi.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000936; C:primary cell septum; IEA:EnsemblFungi.
DR GO; GO:0098552; C:side of membrane; IEA:UniProtKB-KW.
DR GO; GO:0030427; C:site of polarized growth; IEA:EnsemblFungi.
DR GO; GO:0042124; F:1,3-beta-glucanosyltransferase activity; IEA:EnsemblFungi.
DR GO; GO:0071970; P:fungal-type cell wall (1->3)-beta-D-glucan biosynthetic process; IEA:EnsemblFungi.
DR GO; GO:0031505; P:fungal-type cell wall organization; IEA:TreeGrafter.
DR Gene3D; 3.20.20.80; Glycosidases; 1.
DR InterPro; IPR004886; Glucanosyltransferase.
DR InterPro; IPR017853; Glycoside_hydrolase_SF.
DR PANTHER; PTHR31468; 1,3-BETA-GLUCANOSYLTRANSFERASE GAS1; 1.
DR PANTHER; PTHR31468:SF8; 1,3-BETA-GLUCANOSYLTRANSFERASE GAS2; 1.
DR Pfam; PF03198; Glyco_hydro_72; 1.
DR SUPFAM; SSF51445; (Trans)glycosidases; 1.
PE 3: Inferred from homology;
KW Glycoprotein {ECO:0000256|RuleBase:RU361209};
KW GPI-anchor {ECO:0000256|RuleBase:RU361209};
KW Lipoprotein {ECO:0000256|RuleBase:RU361209};
KW Membrane {ECO:0000256|RuleBase:RU361209};
KW Reference proteome {ECO:0000313|Proteomes:UP000008984};
KW Signal {ECO:0000256|RuleBase:RU361209};
KW Transferase {ECO:0000256|RuleBase:RU361209}.
FT SIGNAL 1..19
FT /evidence="ECO:0000256|RuleBase:RU361209"
FT CHAIN 20..374
FT /note="1,3-beta-glucanosyltransferase"
FT /evidence="ECO:0000256|RuleBase:RU361209"
FT /id="PRO_5005130792"
FT NON_TER 374
FT /evidence="ECO:0000313|EMBL:EGR48094.1"
SQ SEQUENCE 374 AA; 41274 MW; F8AA26EC8A2CF10E CRC64;
Query Match 100.0%; Score 2009; Length 374;
Best Local Similarity 100.0%;
Matches 374; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MRWSSVAVALASAKSFAVALDPVSVVGNKFFNKDGSQFFIKGIAYQLVPQDPLVDTDQCK 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MRWSSVAVALASAKSFAVALDPVSVVGNKFFNKDGSQFFIKGIAYQLVPQDPLVDTDQCK 60
Qy 61 RDAKLMAELGTNTIRVYHVDPDADHDGCMSAFDDAGIYVLADLDTFDTYIIPQNNYWNKT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RDAKLMAELGTNTIRVYHVDPDADHDGCMSAFDDAGIYVLADLDTFDTYIIPQNNYWNKT 120
Qy 121 KFDRYAEVLDTFQKYDNLLGVFVGNENIATKDDSPTAPYLKAAARDMKAYRDAQGYREIP 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 KFDRYAEVLDTFQKYDNLLGVFVGNENIATKDDSPTAPYLKAAARDMKAYRDAQGYREIP 180
Qy 181 VGYSAADILQLRPMLQDYLTCGGNSSETVDFFALNSYSWCDPSTYKESTYDQLEAYAKKF 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 VGYSAADILQLRPMLQDYLTCGGNSSETVDFFALNSYSWCDPSTYKESTYDQLEAYAKKF 240
Qy 241 PVPIFLSETGCIVPGPRQFDDQDAIFGPEMVNDWSGAIIYEWIQEENGYGIITYAPAGQA 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 PVPIFLSETGCIVPGPRQFDDQDAIFGPEMVNDWSGAIIYEWIQEENGYGIITYAPAGQA 300
Qy 301 AGPNVEGGFLRKGTPTPKLPDFTALKSKWATNTPTGVSRDDYDAKDVSTRACPSSTAGGW 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 AGPNVEGGFLRKGTPTPKLPDFTALKSKWATNTPTGVSRDDYDAKDVSTRACPSSTAGGW 360
Qy 361 WQVDGDAKLPTLGQ 374
||||||||||||||
Db 361 WQVDGDAKLPTLGQ 374
Sequence Alignment between SEQ ID NO:2 of the instant application (“Query”) and polynucleotide encoding Trichoderma reesei β-(1,3)-glucanosyltransferase of GL985066 (“Sbjct”)
PNG
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2360
1832
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Greyscale
Prosecution Insights