DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
The instant application is a CON of 17/727,934 (filed 25 April 2022), which is a CON of 16/634,027 (filed 24 January 2020), which is a 371 of PCT/US2018/043993 (filed 27 July 2018), and claims benefit of U.S. Provisional applications 62/611,634 (filed 29 December 2017) and 62/537,516 (filed 27 July 2017).
Support for instant claims 24-28, 30-35, and 40-41 can be found in the disclosure of 62/537,516 on at least pg. 14, 18-19, 30-31, and 33. Therefore, the effective filing date of claims 24-28, 30-35, and 40-41 is 27 July 2017.
However, 62/537,516 does not contain support for all limitations of claims 29 (specifically, Mastigocoleus, Chlorogloeopsis, Hapalosiphon, Mastigocladus, or Westiella MAA gene clusters) and 36-39. Support for these claims can be found in the disclosure of 62/611,634 in at least FIGs. 30A and 32A and pg. 39 of the specification. Therefore, the effective filing date of claims 29 and 36-39 is 29 December 2017.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 24 June 2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Objections
Claims 25-29 and 39 are objected to because of the following informalities:
In claim 25, the term “DDGS” should be fully spelled out upon first use in the claims;
In claim 26, the term “DHQS” should be fully spelled out upon first use in the claims;
In claim 27, “ATP grasp” should read “ATP-grasp” to be consistent with the term used throughout the claims;
In claim 28, the term “NRP” should be fully spelled out upon first use in the claims;
In claim 29, “Hapolosiphon MAA gene cluster” is listed in line 3 and line 4; and
In claim 39, “NPR” should read “NRP”.
Appropriate correction is required.
Claim Rejections - 35 USC § 103
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.
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.
Claims 24-30, 33, and 40-41 are rejected under 35 U.S.C. 103 as being unpatentable over Balskus and Walsh (2010, Science; herein “Balskus”) as evidenced by Katoch et al. (2016, Appl. Environ. Microbiol.; herein “Katoch”) in view of Roberts et al. (2009, Chem BioChem; herein “Roberts”) as evidenced by NovoPro (“pGEM-T Easy vector (Cat. No.: V012473)”).
Regarding claim 24, Balskus teaches a method of producing 4-deoxygadusol (Fig. 2C) comprising culturing a recombinant E. coli comprising an expression construct comprising the shinorine biosynthetic gene cluster (i.e., MAA gene cluster) (pg. 1654, left and middle col.).
Regarding claim 25, Balskus teaches that the shinorine biosynthetic gene cluster comprises Ava_3858, which is known in the art as a DDG-synthase (as evidenced by Katoch, FIG. 1), and an O-methyltransferase, Ava_3857 (pg. 1654, left col., para. 2 and Fig. 2).
Regarding claim 26, Balskus teaches that the shinorine biosynthetic gene cluster comprises a DHQS homolog, Ava_3858 (pg. 1654, left col., para. 2 and Fig. 2).
Regarding claim 27, Balskus teaches that the shinorine biosynthetic gene cluster comprises an ATP-grasp homolog, Ava_3856 (pg. 1654, left col., para. 2 and Fig. 2).
Regarding claim 28, Balskus teaches that the shinorine biosynthetic gene cluster comprises a NRPS homolog, Ava_3855 (pg. 1654, left col., para. 2 and Fig. 2).
Regarding claim 29, Balskus teaches that the shinorine biosynthetic gene cluster is an Anabaena MAA gene cluster (pg. 1654, left col., para. 2 and Fig. 2).
However, Balskus does not teach a method comprising culturing a recombinant cyanobacterial cell, wherein the cyanobacterial cell comprises an expression construct comprising a promoter operably linked to a nucleic acid sequence encoding the MAA gene cluster and a PPTase, as in claim 24, a PPTase comprising a nucleic acid sequence selected from any one of SEQ ID NOs: 1-7, as in claim 30, or a recombinant Synechocystis cell, as in claim 41.
Regarding claims 24, 30, 33, and 41, Roberts teaches a recombinant Synechocystis sp. PCC6803 comprising an expression construct made from pGEM-T-Easy (which comprises the lac promoter upstream of the insertion site, as is evidenced by NovoPro) comprising Sppt, which encodes a phosphopantetheinyl transferase identical to that of instant SEQ ID NO: 6 (pg. 1875, left col., para. 4; see Figure 1 for alignment below), and PPTase from the cyanobacterium Nodularia spumigena (pg. 1876, left col., para. 3 and). Roberts also teaches that large multimodular enzymes known as nonribosomal peptide synthetases (NRPS) contain a carrier protein domain that must be activated by PPTase (pg. 1869, left col., para. 2). Roberts teaches that cyanobacteria, including Synechocystis, can be efficient heterologous hosts for the expression of cyanobacterial compounds due to their fast doubling times and well known genetic manipulation methods, as well as a clean expression background due to the lack of biosynthetic gene clusters (pg. 1870, left col., para. 2).
Regarding claim 40, Roberts teaches that Synechocystis sp. PCC6803 does not contain any NRPS and does not contain any biosynthetic gene clusters (such as MAA gene clusters) (pg. 1870, left col., para. 2).
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Figure 1: Alignment of instant SEQ ID NO: 6 (Qy) and the sequence of Sppt (Genbank: BAA10326) taught by Roberts (Db).
Therefore, it would have been prima facie obvious, before the effective filing date of the claimed invention, to a person of ordinary skill in the art, to first modify the method of producing 4-DG taught by Balskus by adding the shinorine gene cluster taught by Balskus to the expression vector comprising the upstream promoter and Sppt gene taught by Roberts, then to use the recombinant Synechocystis sp. PCC6803 taught by Roberts is the host cell in place of the E. coli taught by Balskus, thereby arriving at the invention of claims 24-30, 33, and 40-41. The person of ordinary skill in the art would have been motivated to make the modification because Roberts teaches that PPTase activity is required for the function of nonribosomal peptide synthetases (NRPS), which Balskus teaches is a component of the shinorine biosynthesis pathway. Additionally, Roberts teaches that Synechocystis sp. PCC6803 can be beneficial as a host cell for expression of heterologous cyanobacterial biosynthetic gene clusters because of its fast doubling time and because it does not contain native biosynthetic gene clusters. Therefore, the combination is also desirable (see MPEP 2144(II)). The person of ordinary skill in the art would have had a reasonable expectation of success because Balskus teaches that the shinorine biosynthesis gene cluster can be successfully expressed in a heterologous bacterial host and Roberts teaches that Synechocystis sp. PCC6803 can express genes from other cyanobacteria and that techniques for genetic modification of Synechocystis are well-known in the art (pg. 1870, left col., para. 2). Therefore, the combination leads to expected results because each element performs the same function as is does individually.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that combining prior art elements according to known methods to yield predictable results, is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results. In the instant case, all elements (i.e., recombinant Synechocystis, MAA gene cluster, PPTase, etc.) were known in the art. In addition, combining these elements yields a method/composition wherein each element merely performs the same function as it does separately; thus, the results of the combination would be recognized as predictable to one of ordinary skill in the art. Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Claims 24-41 are rejected under 35 U.S.C. 103 as being unpatentable over Balskus (2010, Science) as evidenced by Katoch (2016, Appl. Environ. Microbiol.) in view of Roberts (2009, Chem BioChem) as evidenced by NovoPro (“pGEM-T Easy vector (Cat. No.: V012473)”) as applied to claims 24-30, 33, and 40-41 above, and further in view of Zhou et al. (2014, Sci. Rep.; herein “Zhou”).
The combination of Balskus as evidenced by Katoch and Roberts in view of NovoPro is set forth in para. 10-21 above and teaches all limitations of claims 24-30, 33, and 40-41.
However, the combination of Balskus and Roberts does not teach a Synechocystis promoter, as in claim 31, the Pcpc560 promoter, PrnpB promoter, or Ptrc promoter, as in claim 32, an expression construct further comprising a second promoter, as in claim 34, or wherein the second promoter is Pcpc560, as in claim 35.
Regarding claims 31-32 and 34-35, Zhou teaches that Pcpc560 is a very strong promoter that results in efficient and strong expression of heterologous genes in cyanobacteria, particularly in Synechocystis sp. PCC6803, which expressed a functional proteins at levels comparable to that of E. coli (Abstract and pg. 4, left col., para. 3).
Therefore, it would have been prima facie obvious, before the effective filing date of the claimed invention, to a person of ordinary skill in the art, to modify the method of producing 4-DG comprising culturing a recombinant Synechocystis sp. PCC6803 comprising an expression construct comprising a promoter operably linked to a shinorine biosynthesis gene cluster and a PPTase as taught by Balskus and Roberts by adding the Pcpc560 promoter to the expression construct, thereby arriving at the invention of claims 24-35 and 40-41. The person of ordinary skill in the art would have been motivated to make the modification because Zhou teaches that the Pcpc560 promoter is a strong promoter in Synechocystis sp. PCC6803 that results in the expression of heterologous proteins at a level comparable to E. coli. Therefore, the combination is also desirable (see MPEP 2144(II)). The person of ordinary skill in the art would have had a reasonable expectation of success because Zhou demonstrates that the Pcpc560 promoter can be used successfully in Synechocystis sp. PCC6803, which is the same strain used by Roberts. Therefore, the combination leads to expected results because each element performs the same function as is does individually.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that combining prior art elements according to known methods to yield predictable results, is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results. In the instant case, all elements (i.e., recombinant Synechocystis, MAA gene cluster, PPTase, Pcpc560 promoter, etc.) were known in the art. In addition, combining these elements yields a method/composition wherein each element merely performs the same function as it does separately; thus, the results of the combination would be recognized as predictable to one of ordinary skill in the art. Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Additionally, it would have been prima facie obvious, before the effective filing date of the claimed invention, to a person of ordinary skill in the art, to duplicate the Pcpc560 promoter taught by Zhou in order to obtain an expression construct comprising three promoters, thereby arriving at the invention of claims 37-38, and to rearrange the location of the promoters and the genes of the shinorine gene cluster to produce an expression construct comprising a second promoter between the O-methyltransferase and ATP-grasp genes and a third promoter between the ATP-grasp and NRPS genes, thereby arriving at the invention of claims 36 and 39. The person of ordinary skill in the art would have been motivated to make the modification because Zhou teaches that the Pcpc560 promoter is a strong promoter in Synechocystis sp. PCC6803 which would result in increased expression of ATP-grasp and NRPS genes. Therefore, the combination is also desirable (see MPEP 2144(II)). The person of ordinary skill in the art would have had a reasonable expectation of success because duplicating the Pcpc560 promoter and rearranging the location of the promoter within the gene cluster does not change the function of the promoter or the genes to which it is linked. Additionally, one of ordinary skill in the art would predict that duplicating and rearranging the location of the promoter would result in an expected increase in expression of the genes to which the Pcpc560 promoter is linked. See MPEP 2144.04(VI)(B) and (C). The specification has not provided any reason to believe that the arrangement of the promoter-gene pairs on the plasmid is critical, or that it is more than merely an arbitrary design choice. Of note, the arrangement of the promoter “between” the two genes could be achieved by flipping the orientation of a gene-promoter pair.
In In re Seid, 161 F.2d 229, 73 USPQ 431 (CCPA 1947) (Claim was directed to an advertising display device comprising a bottle and a hollow member in the shape of a human figure from the waist up which was adapted to fit over and cover the neck of the bottle, wherein the hollow member and the bottle together give the impression of a human body. Appellant argued that certain limitations in the upper part of the body, including the arrangement of the arms, were not taught by the prior art. The court found that matters relating to ornamentation only which have no mechanical function cannot be relied upon to patentably distinguish the claimed invention from the prior art.). In this case, like Seid, the art does not teach the arrangement of the promoter relative to the genes, but there is no mechanical function to the arrangement of the individual gene-promoter pairs relative to the plasmid DNA, so it cannot patentably distinguish the claimed invention from the prior art.
Similarly, in In re Harza, 274 F.2d 669, 124 USPQ 378 (CCPA 1960) (Claims at issue were directed to a water-tight masonry structure wherein a water seal of flexible material fills the joints which form between adjacent pours of concrete. The claimed water seal has a "web" which lies in the joint, and a plurality of "ribs" projecting outwardly from each side of the web into one of the adjacent concrete slabs. The prior art disclosed a flexible water stop for preventing passage of water between masses of concrete in the shape of a plus sign (+). Although the reference did not disclose a plurality of ribs, the court held that mere duplication of parts has no patentable significance unless a new and unexpected result is produced.). In this case, like Harza, the art does not teach a third promoter, including wherein the third promoters are Pcpc560, but there is not a new an unexpected result from using Pcpc560 as a third promoter, so it cannot patentably distinguish the claimed invention from the prior art. Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
US 11,352,601 B2
Claims 24-32, 34-39, and 41 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 6, 10, and 12-14 of U.S. Patent No. 11,352,601 (‘601), either alone or in view of Balskus (2010, Science) as evidenced by Katoch (2016, Appl. Environ. Microbiol.) and Zhou (2014, Sci. Rep.).
Regarding instant claims 24 and 31-32, the ‘601 claims teach a method for producing a chemical compound of interest comprising culturing a recombinant cyanobacterial cell comprising at least one nucleic acid construct encoding a heterologous phosphopantetheinyl transferase (PPTase) (‘601 claims 1, 10, and 14) and that the nucleic acid constructs encoding the heterologous PPTase comprise a constitutive or inducible promoter operably linked to a nucleotide sequence encoding said heterologous PPTase (‘601 claim 4). The ‘601 claims also teach that the recombinant cyanobacterial cells further comprise at least one nucleic acid construct encoding a heterologous shinorine gene cluster (i.e., MAA gene cluster) (‘601 claim 12) which may be under the control of the Synechocystis Pcpc560 promoter (‘601 claim 14).
Regarding instant claim 29, the ’601 claims teach that the heterologous shinorine gene cluster is obtained from a Fischerella sp. (‘601 claim 13).
Regarding instant claim 30, the ‘601 claims teach that the heterologous PPTase may have a nucleic acid sequence of SEQ ID NO: 1, which is identical to instant SEQ ID NO: 1 (‘601 claim 6; see Figure 2 for alignment below).
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Figure 2: Alignment of instant SEQ ID NO: 1 (Qy) with SEQ ID NO:1 from the ‘601 claims (Db).
Regarding instant claim 41, the ‘601 claims teach that the recombinant cyanobacterial cell is a Synechocystis cell (‘601 claims 13-14).
Claims 24, 29-32, and 41 are rejected as anticipated by the ‘601 claims alone.
However, the ‘601 claims do not teach a MAA gene cluster encoding a DDGS homolog and an O-methyltransferase, as in instant claim 25, a MAA gene cluster encoding a DHQS homolog, as in instant claim 26, a MAA gene cluster encoding aa ATP-grasp, as in instant claim 27, or a MAA gene cluster encoding a NRP synthase homolog, as in instant claim 28.
Regarding instant claim 24, Balskus teaches a method of producing 4-deoxygadusol (Fig. 2C) comprising culturing a recombinant E. coli comprising an expression construct comprising the shinorine biosynthetic gene cluster (i.e., MAA gene cluster) (pg. 1654, left and middle col.).
Regarding instant claim 25, Balskus teaches that the shinorine biosynthetic gene cluster comprises Ava_3858, which is known in the art as a DDG-synthase (as evidenced by Katoch, FIG. 1), and an O-methyltransferase, Ava_3857 (pg. 1654, left col., para. 2 and Fig. 2).
Regarding instant claim 26, Balskus teaches that the shinorine biosynthetic gene cluster comprises a DHQS homolog, Ava_3858 (pg. 1654, left col., para. 2 and Fig. 2).
Regarding instant claim 27, Balskus teaches that the shinorine biosynthetic gene cluster comprises an ATP-grasp homolog, Ava_3856 (pg. 1654, left col., para. 2 and Fig. 2).
Regarding instant claim 28, Balskus teaches that the shinorine biosynthetic gene cluster comprises a NRPS homolog, Ava_3855 (pg. 1654, left col., para. 2 and Fig. 2).
Regarding instant claim 29, Balskus teaches that the shinorine biosynthetic gene cluster is an Anabaena MAA gene cluster (pg. 1654, left col., para. 2 and Fig. 2).
Regarding claims 31-32 and 34-35, Zhou teaches that Pcpc560 is a very strong promoter that results in efficient and strong expression of heterologous genes in cyanobacteria, particularly in Synechocystis sp. PCC6803, which expressed a functional proteins at levels comparable to that of E. coli (Abstract and pg. 4, left col., para. 3).
Therefore, it would have been prima facie obvious, to a person of ordinary skill in the art, to substitute the Fischerella shinorine gene cluster taught by the ‘601 claims with the Anabaena MAA cluster taught by Balskus, thereby arriving at the invention of instant claims 24-32 and 41. The person of ordinary skill in the art would have been motivated to make the modification because the Anabaena gene cluster and the functions of each enzyme in the pathway are known in the art to produce 4-DG during the process of producing shinorine. Therefore, the combination is also desirable (see MPEP 2144(II)). The person of ordinary skill in the art would have had a reasonable expectation of success because the ‘601 claims teach that a generic shinorine gene cluster may be used and Balskus teaches that the Anabaena gene cluster may be successfully expressed in a heterologous host cell. Therefore, the combination leads to expected results because each element performs the same function as is does individually.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that the simple substitution of one known element for another to obtain predictable results is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results". In the instant case, the ‘601 claims teach a product or method that only differs from the claimed invention by the substitution of a single component (i.e., substitution of the MAA gene cluster used); the substituted element (i.e., the Anabaena shinorine gene cluster) was already known and already shown to function as a 4-DG and shinorine pathway in a heterologous host, therefore no change in the function of the substituted element occurred; and one of ordinary skill in the art would be capable of substituting one MAA gene cluster for another with a reasonable expectation of success (i.e., the substitution of the element would lead to predictable results). Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Additionally, it would have been prima facie obvious, to a person of ordinary skill in the art, to duplicate the Pcpc560 promoter taught by the ‘601 claims in order to obtain an expression construct comprising two or three promoters, thereby arriving at the invention of claims 34-35 and 37-38, and to rearrange the location of the promoters and the genes of the shinorine gene cluster to produce an expression construct comprising a second promoter between the O-methyltransferase and ATP-grasp genes and a third promoter between the ATP-grasp and NRPS genes, thereby arriving at the invention of claims 36 and 39. The person of ordinary skill in the art would have been motivated to make the modification because Zhou teaches that the Pcpc560 promoter is a strong promoter in Synechocystis sp. PCC6803 which would result in increased expression of ATP-grasp and NRPS genes. Therefore, the combination is also desirable (see MPEP 2144(II)). The person of ordinary skill in the art would have had a reasonable expectation of success because duplicating the Pcpc560 promoter and rearranging the location of the promoter within the gene cluster does not change the function of the promoter or the genes to which it is linked. Additionally, one of ordinary skill in the art would predict that duplicating and rearranging the location of the promoter would result in an expected increase in expression of the genes to which the Pcpc560 promoter is linked. See MPEP 2144.04(VI)(B) and (C). The specification has not provided any reason to believe that the arrangement of the promoter-gene pairs on the plasmid is critical, or that it is more than merely an arbitrary design choice. Of note, the arrangement of the promoter “between” the two genes could be achieved by flipping the orientation of a gene-promoter pair.
In In re Seid, 161 F.2d 229, 73 USPQ 431 (CCPA 1947) (Claim was directed to an advertising display device comprising a bottle and a hollow member in the shape of a human figure from the waist up which was adapted to fit over and cover the neck of the bottle, wherein the hollow member and the bottle together give the impression of a human body. Appellant argued that certain limitations in the upper part of the body, including the arrangement of the arms, were not taught by the prior art. The court found that matters relating to ornamentation only which have no mechanical function cannot be relied upon to patentably distinguish the claimed invention from the prior art.). In this case, like Seid, the art does not teach the arrangement of the promoter relative to the genes, but there is no mechanical function to the arrangement of the individual gene-promoter pairs relative to the plasmid DNA, so it cannot patentably distinguish the claimed invention from the prior art.
Similarly, in In re Harza, 274 F.2d 669, 124 USPQ 378 (CCPA 1960) (Claims at issue were directed to a water-tight masonry structure wherein a water seal of flexible material fills the joints which form between adjacent pours of concrete. The claimed water seal has a "web" which lies in the joint, and a plurality of "ribs" projecting outwardly from each side of the web into one of the adjacent concrete slabs. The prior art disclosed a flexible water stop for preventing passage of water between masses of concrete in the shape of a plus sign (+). Although the reference did not disclose a plurality of ribs, the court held that mere duplication of parts has no patentable significance unless a new and unexpected result is produced.). In this case, like Harza, the art does not teach a third promoter, including wherein the third promoters are Pcpc560, but there is not a new an unexpected result from using Pcpc560 as a third promoter, so it cannot patentably distinguish the claimed invention from the prior art. Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
US 11,970,689 B2
Claims 24-41 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,970,689 (‘689). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding instant claim 24, the ‘689 claims teach a method for producing shinorine, comprising culturing a recombinant cyanobacterial cell comprising an expression construct comprising a promoter operably linked to a nucleic acid sequence encoding a shinorine gene cluster (i.e., MAA gene cluster) and a phosphopantetheinyl transferase (PPT) (‘689 claims 1, 13, and 17). Regarding the phrase “A method for producing 4-Deoxygadusol (4-DG)” in instant claim 24, a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.
Regarding instant claim 25, the ‘689 claims teach that the shinorine gene cluster comprises FsA, a DDGS homologue as evidenced by Table 3 of ‘689, and FsB, an O-methyltransferase as evidenced by FIG. 22 of ‘689 (‘689 claim 1). See MPEP 804(II)(B)(1): “The specification can be used as a dictionary to learn the meaning of a term in the claim. Toro Co. v. White Consol. Indus., Inc., 199 F.3d 1295, 1299, 53 USPQ2d 1065, 1067 (Fed. Cir. 1999).”
Regarding instant claim 26, the ‘689 claims teach that the shinorine gene cluster comprises FsA (‘689 claim 1), a DHQS homologue as evidenced by FIG. 22 of ‘689.
Regarding instant claim 27, the ‘689 claims teach that the shinorine gene cluster comprises FsC (‘689 claim 1), an ATP-grasp homologue as evidenced by FIG. 22 of ‘689.
Regarding instant claim 28, the ‘689 claims teach that the shinorine gene cluster comprises FsD (‘689 claim 1), a NRPS as evidenced by FIG. 22 of ‘689.
Regarding instant claim 29, the ‘689 claims teach that the shinorine gene cluster is a Fischerella MAA gene cluster (‘689 claim 1).
Regarding instant claim 30, the ‘689 claims teach that the PPT is APPT from Anabaena sp. PCC7120 (‘689 claim 1), which is identical to instant SEQ ID NO: 1 as evidenced by the table in col. 12 of ‘689 (see Figure 3 for alignment below).
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Figure 3: Alignment of instant SEQ ID NO: 1 (Qy) with APPT, i.e., SEQ ID NO: 1 from ‘689 (Db).
Regarding instant claim 31, the ‘689 claims teach that the promoter is a Synechocystis promoter (‘689 claim 2).
Regarding instant claim 32, the ‘689 claims teach that the Synechocystis promoter is a PrnpB promoter, a Pcpc560 promoter (‘689 claim 3), or a Ptrc promoter (‘689 claim 5).
Regarding instant claim 33, the ‘689 claims teach that the promoter is positioned upstream relative to the nucleic acid sequence encoding the Fischerella shinorine gene cluster (‘689 claim 6).
Regarding instant claim 34, the ‘689 claims teach that the expression construct further comprises a second promoter (‘689 claims 7 and 19).
Regarding instant claim 35, the ‘689 claims teach that the second promoter is a Pcpc560 promoter (‘689 claims 9 and 20).
Regarding instant claim 36, the ‘689 claims teach that the second promoter is positioned between a nucleic acid sequence encoding FsB (O-methyltransferase) and a nucleic acid sequence encoding FsC (ATP-grasp) (‘689 claim 8).
Regarding instant claim 37, the ‘689 claims teach that the expression construct further comprises a third promoter (‘689 claims 10 and 19).
Regarding instant claim 38, the ‘689 claims teach that the third promoter is a Pcpc560 promoter (‘689 claims 12 and 20).
Regarding instant claim 39, the ‘689 claims teach that the third promoter is positioned between a nucleic acid sequence encoding FsC (ATP-grasp) and a nucleic acid sequence encoding FsD (NRP synthase) (‘689 claim 11).
Regarding instant claim 40, the ‘689 claims teach that the recombinant cyanobacterial cell does not comprise a native shinorine gene cluster (‘689 claim 14).
Regarding instant claim 41, the ‘689 claims teach that the recombinant cyanobacterial cell is a Synechocystis cell (‘689 claims 15 and 18).
Conclusion
No claim is allowed.
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/BAILEY M MORGAN/Examiner, Art Unit 1645
/SAMIRA J JEAN-LOUIS/Supervisory Patent Examiner, Art Unit 1642
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