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 .
Claim Status
The amendment of 02/27/2026 has been entered (Claim set as filed on 02/27/2026). Claims 1-22 are pending. Claims 5-22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 previously elected invention Group I, drawn to an enzyme variant, and the species ‘enzyme variant of claim 1 comprising at least V24I and S256G substitutions’, without traverse, in the reply filed on 09/24/2024.
Claims 1-4 are currently under examination and were examined on their merits.
Withdrawn Objections/Rejections
The rejection of claims 1-4 under 35 U.S.C. 112(b) set forth in the previous Office action is withdrawn in light of Applicant’s amendment filed on 02/27/2026.
The rejection of claims 1-4 under 35 U.S.C. 103 set forth in the previous Office action filed is withdrawn in light of Applicant’s Declarations under 37 CFR 1.132 filed on 02/27/2026 and 06/09/2025. The results presented in the declarations provide evidence that mannanase variants comprising a substitution in position S256 have increased activity compared to the parent mannanase.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-4 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 claims contain 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
As stated in MPEP 2111.01, during examination, the claims must be interpreted as broadly as their terms reasonably allow. Claims 1-4 are directed in part to a genus of mannanase variants of the polypeptides of SEQ ID NO: 1 that have any structure or have at least 90% to less than 100% sequence identity to the polypeptide of SEQ ID NO: 1, and further require a substitution in position S256.
In University of California v. Eli Lilly & Co., 43 USPQ2d 1938, the Court of Appeals for the Federal Circuit has held that “A written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula, [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials”. As indicated in MPEP § 2163, 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 that Applicant was in possession of the claimed genus. In addition, MPEP § 2163 states that a representative number of species means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
There is either (a) no structural limitation, or (b) a significant amount of structural variability with respect to the members of the genus of mannanase proteins required by the claims. While the specification in the instant application discloses the structure of the mannanase protein of SEQ ID NO: 1, it provides no clue as to the structural elements required in any mannanase protein, nor does it teach which structural elements within SEQ ID NO: 1 with substitution of S256 are required in any mannanase protein. Moreover, while the claims require mannanase variants having enhanced functional properties compared to the polypeptide of SEQ ID NO: 1, the specification and the prior art are silent to those structural features in any mannanase protein, that are associated with these functional properties. No disclosure of a structure/function correlation has been provided which would allow one of skill in the art to recognize which variants of the polypeptide of SEQ ID NO: 1 comprising the claimed substitution S256 and having the recited % sequence identity have the desired mannanase activity and the desired enhanced functional properties.
The claims encompass a large genus of proteins which are structurally unrelated or substantially unrelated in structure. A polypeptide having 90% sequence identity with the polypeptide of SEQ ID NO: 1 allows for any combination of about 28 amino acid modifications within SEQ ID NO: 1 (28.9 = 0.1x289; SEQ ID NO: 1 has 289 amino acids). The total number of variants of a polypeptide having a specific number of amino acid substitutions can be calculated from the formula N!x19A/(N-A)!/A!, where N is the length in amino acids of the reference polypeptide and A is the number of allowed substitutions. Thus, the total number of variants of the polypeptide of SEQ ID NO: 1 having 90% sequence identity to the polypeptide of SEQ ID NO: 1 that result from amino acid substitutions is 289!x1928/(289-28)!/28! or 4.36x1074 variants.
A sufficient written description of a genus of polypeptides may be achieved by a recitation of a representative number of polypeptides defined by their amino acid sequence or a recitation of structural features common to members of the genus, which features constitute a substantial portion of the genus. However, in the instant case, there is either no recited structural feature which is representative of all the members of the genus of proteins recited, or the recited structural feature, i.e., 90% sequence identity to SEQ ID NO: 1 and a substitution in position 256 is not representative of all the members of the genus of mannanase recited since there is no information as to which are the structural elements within the polypeptide of SEQ ID NO: 1 that are essential for the recited activity, which are the remaining structural elements required in the recited polypeptides in addition to those recited in the claims such that the desired mannan degrading activity is displayed, or a correlation between structure and function which would provide those unknown structural features. Furthermore, while one could argue that the species disclosed are representative of the structure of all the members of the genus, it is noted that the instant specification only discloses variant sequences comprising the substitutions S256G or S256A and up to two additional substitutions (V24I and V123I) with demonstrated increased activity (see variants CM124, CM201, CM204, and CM206 in Table 1, Example 3, and in Figures 3A and 3B). However, the claimed mannanase variant allows for any amino acid substitution in position S256 and for up to about 27 substitutions in addition to the substitution in position S256.
Table 1 in the specification lists additional variants which apart from variants CM124, CM201, CM204, and CM206, are not discussed regarding their mannan degrading activities. Further, Figures 3A and 3B show that adding a substitution, i.e. V24I, to the S256G substitution appears to lower the activity of the mannanase comprising a S256G substitution. Tailford et al. (“Understanding How Diverse β-Mannanases Recognize Heterogeneous Substrates”, published in 2009, Biochemistry 2009, Vol. 48, pages 7009-7018) discloses wherein a single mutation can lead to strongly reduced mannanase activity (page 7013, right column, paragraph 1; see Table 4). Therefore, since minor structural differences may result in changes affecting function, and no additional information correlating structure with the desired functional characteristics has been provided, it is unclear which S256 substitutions apart from S256G and S256A result in increased mannan degrading activity, and which additional substitutions apart from V24I and V123I can be combined with a S256 substitution to provide a mannanase variant as required by the claims.
As such, a skilled artisan cannot reasonably conclude that the species disclosed are representative of the structure of all the mannanase proteins required by the claims. Due to the fact that the specification only discloses a limited number of species of the genus of mannanase proteins required by the claims, and the lack of description of any additional species by any relevant, identifying characteristics or properties, one of skill in the art would not recognize from the disclosure that Applicant was in possession of the claimed invention.
Closest prior art
Regarding claims 1-4, the closest prior art to the claimed invention is provided by the teachings of Kauppinen et al. (US 2003/0203466 A 1, published on 10/30/2003), hereinafter ‘Kauppinen’.
Kauppinen teaches a mannanase sequence (SEQ ID NO: 22; 320 aa; paragraph [0083]; see sequence on page 71) having 94.6% identity with instant SEQ ID NO: 1. Kauppinen further teaches mannanase variants comprising conservative amino acid substitutions (paragraphs [0089], [0100], and [0106]).
Kauppinen does not teach wherein a mannanase variant comprises a substitution of an amino acid in position S256, and wherein a mannanase variant has increased mannan degrading activity compared to the mannanase comprising SEQ ID NO: 1.
Conclusion
No claims are allowed.
Correspondence Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SANDRA ZINGARELLI whose telephone number is (703)756-1799. The examiner can normally be reached M-F 9-5.
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/SANDRA ZINGARELLI/ Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
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