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 .
Second Action Non-Final
It is noted that this Office action is a Second Action Non-Final. The Office is re-opening
prosecution to make a new rejection over the position that any mutation introduced in any gene location that disrupts the binding of LD-LDI is rendered obvious.
Status of Claims
The amendments received on 02/13/2026 have been entered. Claims 1-4, 6-10, and 12-19 are pending.
Claims 3-4, 6-9, and 12-19 remain withdrawn for being directed to a non-elected invention(s).
Claims 1 and 2 have been amended.
Claims 1, 2, and 10 are examined in this office action.
Objections/Rejections that are Withdrawn
The objection to claim 1 has been withdrawn in light of Applicant’s amendment to the claim.
The 35 USC 112(a) Indefiniteness rejection of claims 1, 2, and 10 has been withdrawn in light of Applicant’s amendment to claim 1.
The 35 USC 112(a) Written Description rejection of claim 2 has been withdrawn in light of Applicant’s amendment to claim 2.
The 35 USC 112(d) Failure to Further Limit rejection of claim 2 has been withdrawn in light of Applicant’s amendment to claim 2.
The 35 USC 102 rejection of claim 10 has been withdrawn in light of Applicant’s accompanying arguments.
The text of those sections of Title 35, U.S. Code, not included in this action, can be found in the prior Non-Final Office action dated 05/05/2025.
Claim Rejections - 35 USC § 103
Claims 1-2 are rejected under 35 U.S.C. 103 as being unpatentable over Morris (Morris et al., International Publication Number: WO 2004/112468 A1, International Publication Date: 29 December 2004) (included on IDS 02/28/2023) in view of Møller (Møller et al., 2015, Plant Biology, Vol. 290(20), pp. 12614-12629) (included on IDS 02/28/2023).
Claim 1 recites “a barley plant, or a part thereof, wherein said barley plant carries a mutation in the HvLDI gene, wherein said mutated HvLDI gene encodes a mutant HvLDI polypeptide having reduced HvLDI inhibitory activity relative to a wild-type (wt) HvLDI polypeptide, wherein the mutation is one of the following mutations
a. a missense mutation resulting in a change from a proline to a different amino acid at position 60 of SEQ ID NO: 1; or
b. a missense mutation resulting in a change from a negatively charged amino acid to a non- negatively charged amino acid in an alpha helix region of mutant HvLDI polypeptide, wherein the alpha helix region comprises amino acids corresponding to positions 63-76 of SEQ ID NO:1, and
wherein grains or germinated grains or malt obtained from said barley plant or part thereof have a free HvLD activity at least 20% higher compared to the free HvLD activity measured in grains obtained from a barley plant carrying a HvLDI gene encoding a wild type (wt) HvLDI polypeptide, but otherwise of the same genotype, when cultivated and prepared under the same conditions.”
Morris teaches that during germination, LD is found in a "free" and an inactive "bound" form, which can be released and activated by treatment with reducing agents, which may activate proteases. It is thought that bound LD may be a limiting factor in the conversion of starch to sugars during malting and hence contribute to the efficiency of the conversion of starch to alcohol in brewing. Bound LD is thought to be complexed with limit dextrinase inhibitor (LDI). The deduced sequence of a barley cDNA has a proposed structure consisting of four α-helices joined by loops with four intramolecular disulphide bonds and one free cysteine. Modification of this inhibitor activity may alter the malting quality of barley (page 4, last paragraph).
Morris teaches the isolation of barley limit dextrinase inhibitor cDNA fragments (Example 2, page 40). The sequence of this cDNA clone is SEQ ID No 1; there are five single base pair substitutions (i.e., mutation in the HvLDI gene), which in turn lead to two amino acid substitutions (i.e., mutant HvLDI polypeptide; SEQ ID No. 2) (Example 2, page 41) (see alignment below).
Morris teaches that stable transformation of half immature embryos (IEs) of barley (i.e., a barley plant, or a part thereof) was performed (Example 4, page 41). Western blot analysis of LDI from mature barley grains showed protein expression (Example 6, page 44).
ALIGNMENT OF MORRIS SEQ ID NO:2 WITH INSTANT SEQ ID NO:1
ADW72761
24-MAR-2005
Barley limit dextrinase inhibitor, SEQ ID 2.
Hordeum vulgare.
WO2004112468-A1.
Morris PC, Stahl Y;
Query Match 100.0%;
Qy 1 MASDHRRFVLSGAVLLSVLAVAAATLESVKDECQPGVDFPHNPLATCHTYVIKRVCGRGP 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MASDHRRFVLSGAVLLSVLAVAAATLESVKDECQPGVDFPHNPLATCHTYVIKRVCGRGP 60
Qy 61 SRPMLVKERCCRELAAVPDHCRCEALRILMDGVRTPEGRVVEGRLGDRRDCPREEQRAFA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 SRPMLVKERCCRELAAVPDHCRCEALRILMDGVRTPEGRVVEGRLGDRRDCPREEQRAFA 120
Qy 121 ATLVTAAECNLSSVQEPGVRLVLLADG 147
|||||||||||||||||||||||||||
Db 121 ATLVTAAECNLSSVQEPGVRLVLLADG 147
Morris does not explicitly teach the mutations in the positions of instant SEQ ID NO: 1 as required by claim 1.
However, Møller teaches that LDI suppresses the LD activity in barley seeds during the early stages of germination. It belongs to the family of cereal type inhibitors (CTIs) sharing a common fold of four α-helices connected by irregular loops and stabilized by either four or five disulfide bonds. CTIs are widespread in cereals and participate in physiologically important processes (page 12615, left column, first full paragraph).
Møller teaches the LDI protein of wheat (which shares 100% sequence identity to instant sequence SEQ ID NO: 1; see sequence alignment below); the secondary structure of LDI is indicated above the alignment, disulfides are numbered 1–4 (below alignment), and the fifth cysteine pair (lacking in LDI-like proteins) is indicated by a green × under the conserved cysteine and a red box around the non-conserved cysteine, as well as an ×. The LDI residues mutated in this study are marked by asterisks.
PNG
media_image1.png
343
1025
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Greyscale
Møller Hordeum vulgare LDI Sequence ABB88573 Aligned with instant Sequence SEQ ID NO: 1
Qy 1 MASDHRRFVLSGAVLLSVLAVAAATLESVKDECQPGVDFPHNPLATCHTYVIKRVCGRGP 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MASDHRRFVLSGAVLLSVLAVAAATLESVKDECQPGVDFPHNPLATCHTYVIKRVCGRGP 60
Qy 61 SRPMLVKERCCRELAAVPDHCRCEALRILMDGVRTPEGRVVEGRLGDRRDCPREEQRAFA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 SRPMLVKERCCRELAAVPDHCRCEALRILMDGVRTPEGRVVEGRLGDRRDCPREEQRAFA 120
Qy 121 ATLVTAAECNLSSVQEPGVRLVLLADG 147
|||||||||||||||||||||||||||
Db 121 ATLVTAAECNLSSVQEPGVRLVLLADG 147
Møller teaches that an examination of the LD-LDI interface for residues involved in the complex formation guided the selection of Arg34, Arg38, Leu41, and Val42 in LDI for mutational analysis (page 12621, left column, last paragraph). In total, seven variants of LDI were made based on the protein-protein interactions: the single R34A, R38A, R38W, L41G, L41W, V42D, and the L41G-V42D variant (i.e., a mutation in the HvLDI gene) (page 12621, right column, first full paragraph).
Møller further teaches amino acids of the HvLDI protein and their positions where an introduced mutation would most disrupt the LDI-LD bond and result in a loss of bonding function (positions 45, 52, 77, 78, 84, and 85) (Table 4, page 12619). Although Møller does not explicitly teach a missense mutation resulting in a change from a proline to a different amino acid mutation at position 60 of instant SEQ ID NO: 1 or a missense mutation resulting in a change from a negatively charged amino acid in an alpha helix region corresponding to positions 63-76 of instant SEQ ID NO: 1 as required by claim 1, it is noted that, paralleling the teachings of Møller, the Applicant has previously claimed mutations in the loop region at position 25-44, a position expressly taught by Møller. Thus, the instantly claimed mutations are embodiments that would be considered a design choice that would be readily apparent to one of ordinary skill in the art. It is noted that the instantly claimed mutations do not appear to be associated with any unexpected results or criticality.
It is noted that it is the position of this Office that any mutation introduced in any gene location that disrupts the binding of LD-LDI is rendered obvious by the teachings of Morris and Møller. A barley plant comprising the mutations of the instant invention would not be distinguishable from a barley plant comprising any of the mutations as taught by Morris and Møller.
At the time the instant application was filed, it would have been obvious and within the scope of one having ordinary skill in the art to use the HvLDI gene as taught by Morris and Møller, to introduce mutations in one or more of the loop regions and/or the alpha helix regions of the HvLDI polypeptide as taught by Møller, to arrive at a barley plant with a mutation in the HvLDI gene encoding a mutant HvLDI polypeptide with a mutation in a region of instant SEQ ID NO: 1 as required by claim 1. One would have been motivated to introduce mutations in the HvLDI gene in order to disrupt the LD-LDI binding mode to regulate the efficiency of the conversion of starch to sugar, as taught by Møller. Taken together, the teachings of Morris and Møller provide one of ordinary skill in the art with the target gene comprising a finite number of target sites. One having ordinary skill in the art would have a high expectation of success by following the teachings of Morris and Møller.
In regard to claim 2, Morris and Møller teach the Barley limit dextrinase inhibitor (SEQ ID NO: 2; ABB88573, respectively) which shares 100% sequence identity with instant sequence SEQ ID NO: 1 (see alignment above), apart from the mutations in the specified positions.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Morris (Morris et al., International Publication Number: WO 2004/112468 A1, International Publication Date: 29 December 2004) (included on IDS 02/28/2023) and Møller (Møller et al., 2015, Plant Biology, Vol. 290(20), pp. 12614-12629) (included on IDS 02/28/2023) as applied to claims 1 and 2 above, in further view of Wasdovitch (Wasdovitch, B., 2014, https://www.brewingwithbriess.com/blog/part-iv-do-you-like-yours-kilned-roasted-or-both).
Claim 10 recites “[a] plant product comprising the barley plant or a part thereof according to claim 1, wherein the plant product is a kiln dried malt prepared from grains of said barley plant”.
Morris and Møller teach the barley plant or a part thereof according to claim 1.
Neither Morris nor Møller teach a plant product that is a kiln dried malt prepared from grains of said barley plant.
Wasdovitch teaches that drying is the third and final step in the malting process, after steeping and germination. Drying is a critical step that stops germination. If germination continued, the kernel would continue to grow and all of the starch reserves needed by the brewer would be used by the growing plant.
On its way to drying, barley is first steeped for two days, then spends the next four days in the germination compartment where the growing kernels undergo modification—the breakdown of complex proteins and carbohydrates which opens up the starch reserves needed for brewing. After the fourth day the barley is now called “green malt” and ready to be transferred to a kiln or roaster to stop germination.
Base malts are kiln dried, typically for 2-4 hours with a finish heat of 180-190° F. This develops flavors ranging from very light malty to subtle malty while retaining enzymes necessary for brewing. Specialty malts are dried in a kiln at higher temperatures for longer periods of time, roasted, or both. This develops the unique flavor, color and other characteristics of each specialty malt.
The majority of malt—base and specialty—is kiln dried. Our ancient ancestors relied upon the sun’s rays to do the job. From wood to coal to natural gas, advances in fuel source and technology have greatly improved the amount of control maltsters have in the kiln. As a result, an exciting variety of kilned malts from Pilsner to Munich-styles are now available for American craft and home brewers alike.
At the time the instant application was filed, it would have been obvious and within the scope of one having ordinary skill in the art to use the barley plant or a part thereof as taught by Morris and Møller, to make the kiln dried malt product as taught by Wasdovitch. One would have been motivated to use the barley plant or a part thereof as taught by Morris and Møller, to make the kiln dried malt product as taught by Wasdovitch knowing that bound LD may be a limiting factor in the conversion of starch to sugars during malting and hence contribute to the efficiency of the conversion of starch to alcohol in brewing, as taught by Morris. Thus, one having ordinary skill in the art would have a high expectation of success by following the teachings of Morris, Møller, and Wasdovitch.
Summary
No claim is allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINA MEADOWS whose telephone number is (703)756-1430. The examiner can normally be reached Monday - Friday 9:00 am - 5:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amjad Abraham can be reached on 571-270-7058. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CHRISTINA L MEADOWS/Examiner, Art Unit 1663
CHRISTINA MEADOWS
Examiner
Art Unit 1663
/Amjad Abraham/SPE, Art Unit 1663
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