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 .
Response to Arguments
The Applicant has provided arguments, in response to the most recent Office Action, and amendments to the claims, dated 2/5/2026.
On page 6 of the Applicant’s Arguments, the Applicant indicates that claim 11 has been canceled. As such, the 35 USC 112(d) rejection on the claim is moot, and hereby withdrawn.
On page 8 of the Applicant’s Arguments, the Applicant states that the amendment to the independent claim provides for a claim that is eligible under 35 USC101, because the claim now recites “recombinant enzyme.” This limitation does not improve the eligibly of the claim under 35 USC 101. Even if a cell is created to recombinantly produce an enzyme that is not natural to it, it does not make the enzyme, per se, unnatural. This can be demonstrated in Association for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 591-94, 106 USPQ2d 1972, 1979-81 (2013) wherein the BRCA1 sequence, per se, was considered natural, regardless of where it was located and how it was produced/isolated. For example, if a yeast cell is engineered to produce human insulin, the insulin appears identical to human insulin and would still be considered a product of nature; this is because its direct counterpart: human insulin, is objectively identical in sequence, structure, and function. See Diamond v. Chakrabarty, 447 U.S. 303, 310, 206 USPQ 193, 197 (1980) and MPEP 2106.04(c). As such, even if an enzyme is produced recombinantly, unless the Applicant can provide evidence of objective differences between the naturally occurring enzyme, and one with the same sequence, but recombinantly produced, the claimed “recombinant enzyme” can still be considered a product of nature, since a “recombinant enzyme” includes natural enzymes that are produced in organisms that they are not natural to.
On page 9 of the Applicant’s Arguments, the Applicant states that Example 13 of the 35 USC 101 eligibly guide suggests that the claimed composition should be eligible. As discussed in the previous paragraph, the claim is drawn to a recombinant enzyme, that can include recombinantly produced, enzymes that possess a natural sequence. Barring claims drawn to a specifically mutated enzyme that does not appear like its natural counterpart, the claims continue to include a product of nature. The cited example does not apply because the example is drawn to a whole engineered cell that includes both natural and non-natural components. Comparing this to the claimed enzyme, unless there is evidence to support a showing that this recombinant enzyme is markedly different, it continues to appear natural, because the sequence is identical to its natural counterpart. The claim must either include a non-naturally occurring sequence for the recombinant enzyme to be considered anything other than a product of nature, or show that the process of producing these enzyme recombinantly materially affects their structure and/or function. For example, if recombinantly inserting a Trichoderma reesei cellulase into a Saccharomyces cerevisiae results in a cellulase enzyme with greater activity, this would provide evidence that the claimed recombinant enzyme is markedly different than its natural counterpart. Barring evidence, a naturally occurring enzyme, regardless of how it is made, is considered the same as any other enzyme with an identical amino acid sequence.
On page 9 of the Applicant’s Arguments, the Applicant suggests that new claim 16 should be eligible under 35 USC 101. Based upon the claim limitation, this claim would not be rejected under 35 USC 101.
On pages 9 and 10 of the Applicant’s Arguments, the Applicant points to claims 16 and 17 as being eligible under 35 USC 101. This is not a correct assumption based upon the rationale provided in previous paragraphs. See the Trichoderma reesei and Saccharomyces cerevisiae example, above.
On pages 10-12 of the Applicant’s Arguments, the Applicant states that the new “recombinant enzyme” limitation provides for claims that do not read upon the cited prior art. While it is true that the prior art teaches naturally occurring enzymes, based upon the above-arguments regarding recombinantly produced naturally occurring enzymes, the prior art continues to read upon the claims. For example, if a skilled artisan were to take a sample of Yazdani’s enzyme composition, and that claimed, it is unclear if the skilled artisan would be capable of distinguishing any differences. If the skilled artisan cannot distinguish any differences between the claimed composition and that of the prior art, the prior art must have anticipated the claimed composition (35 USC 102); additionally, if there is evidence to support the fact that the claimed composition provides for an enzyme that is different that those disclosed in Yazdani, if a substrate were placed in Yazdani’s enzyme composition, and the same substrate were placed in the claimed composition, there is a reasonable expectation that they will yield the same product, with similar kinetics, because the claimed composition would be an obvious variant of Yazdani. That is to say, the function and kinetics of the enzyme classes disclosed in Yazdani are exceptionally well-studied and highly predictable; the ordinary artisan would be wholly capable of reproducing obvious variants of Yazdani’s composition using Yazdani and knowledge generally available to the ordinary artisan. The claims composition would be included in one of these obvious variants. This is highlighted by the fact that there is no evidence to suggest that the claimed composition provides for any products or kinetics that are not already discussed in the prior art.
On page 13 of the Applicant’s Arguments, the Applicant continues to discuss the newly added “recombinant enzyme” limitation. As discussed above, there does not appear to be any fundamental difference between the structure and function of the claimed enzyme, compared to Yazdani, and as such, they can be considered the same or obvious variants. There is no evidence to suggest that the claimed recombinantly produced enzyme is any different than its naturally occurring counterpart. As discussed above, a recombinantly produced enzyme, that provides for a naturally occurring sequence, would be equivalent to its naturally-produced counterpart. If Yazdani’s Penicillium enzymes are recombinantly produced in a yeast cell, the structure, function, kinetics of the enzyme should all be the same; this makes the natural enzyme and the recombinant enzyme indistinguishable from each other, and as such, the same.
On page 14 of the Applicant’s Arguments, the Applicant states that recombinantly produced glucoamylase from Rasamsonia yields unexpected results. In addition to there being no claims limiting the enzyme to that of Rasamsonia, the instant specificaition indicates that Penicillium glucoamylase is within the scope of the claims, and there is nothing in the claim to suggest that any source of glucoamylase is relevant, regardless of species, or even kingdom; that is to say, human glucoamylase can technically read upon the claimed glucoamylase.
On page 14 of the Applicant’s Arguments, the Applicant points to rations that allegedly provide for unexpected results. First, Yazdani provides for enzymes that are administered at the claimed ratios, wherein endoglucanase comprises 2-25% of the composition and glucoamylase provides for 8-15%. See column 4, lines 29-40. For example, a composition that is 25% endoglucanase and 15% glucoamylase provides for a fraction relative to the glucoamylase and the endoglucanase wherein REG is 0.625 (25/[25+15] = 0.625) and RGA is 0.375 (15/[25+15] = 0.375). Second, both of the claimed enzyme-types are well studied, wherein their substrate-product interactions are known, and their kinetics are also known. If the ordinary artisan knows the substrate-product interaction of an enzyme, and the rate at which this conversion occurs would provide the ordinary artisan will ample knowledge to provide for the claimed ratios, especially given that Yazdani provides for an overlapping range. The cited variation among ratios would be an expectation of the ordinary artisan because of their knowledge of enzymatic. The Applicant should be reminded that the ordinary artisan is not a layperson, but rather an individual that possesses either a Masters or PhD in a related field of enzymatic, and further possesses ample applied experience. See MPEP 2141.03. As such, knowledge of substrate-product interactions, and kinetics, would be an expectation of the ordinary artisan.
On page 15 of the Applicant’s Arguments, the Applicant reiterates that the claim is now limited to “recombinant enzymes.” This has been discussed above.
On page 16 of the Applicant’s Arguments, the Applicant contends that the claimed enzyme loading amount, in conjunction with the claimed ratio, provides for unexpected results. As discussed in the rejection, the enzyme loading amount is nothing more than routine optimization, wherein the achieved improvements would be expected by the ordinary artisan. Furthermore, the claimed ratio is provided in the ranges disclosed in Yazdani.
On page 16 of the Applicant’s Arguments, the Applicant claims synergistic results. It is unclear how these would not inherently be present in the composition and method of Yazdani. Yazdani provides for enzymes that are consistent with those claimed, and describes them in ratios that overlap the claimed ratios. As such, any claimed synergism would also be present in Yazdani.
On page 17 of the Applicant’s Arguments, the Applicant discusses “recombinant enzymes” and the unexpected results. All of this has been discussed in the previous paragraphs.
On page 17 of the Applicant’s Arguments, the Applicant points to sulfuric acid pretreatment methods that yield unexpected results. As discussed in Tolan, pretreatment methods are routine in the art; this is underscored by the fact that Yazdani provides results of pretreated biomass. There is nothing unexpected about pretreatment methods, as they will predictably provide for more substrate for the enzymes to utilize, by breaking down macromolecule structures, like crystalline cellulose and lignin.
On pages 18 and 19 of the Applicant’s Arguments, the Applicant discusses the new claims. These will be discussed in the rejections below.
All claims are currently rejection. The 35 USC 112(d) rejection has been withdrawn. The 35 USC 101 rejection has been expanded to include new claims. The 35 USC 102 and 103 rejections will be modified to account for the new claims and limitations.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 16 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 16 is indefinite because it is unclear what amount of mutations, deletions, and/or insertion would be considered within the scope of the claimed invention. Obviously, there is a reasonable expectation that the enzyme must be functional, but the inventors should not be entitled to enzymes that they never discovered, tested, or envisioned. There is no clear direction as to what types of mutations would be consistent with the limitation, nor are there reasonable examples of whether mutations can be conservative or not. Based upon the lack of guidance, it is unclear what specific enzymes the claim should be limited to, and the total extent of mutation along the sequence.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-8 and 17-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more. The claim(s) recite(s) two naturally occurring enzymes, with a third naturally occurring enzyme claimed in a dependent claim (claim 6). This judicial exception is not integrated into a practical application because the claims are drawn to a composition comprising naturally occurring enzymes, wherein the combination of these enzymes does not appear to materially change the individual action of each enzyme involved.
The independent claim provides for a two-enzyme composition, wherein the enzymes are provided in a ratio range, relative to each other. The independent claim involves naturally occurring glucoamylase, and naturally occurring endoglucanase. Glucosidase is a hydrolytic enzyme that breaks terminal glycosidic bonds and liberates a glucose monomer; the claims and instant specification do not suggest that the enzyme performs any function other than its natural function. Endoglucanase are a class of enzymes that are generally considered cellulase-type enzymes, wherein the enzyme hydrolyzes cellulose into smaller subunits; the claims and instant specification do not suggest that the enzyme performs any function other than its natural function. The claims provide for a ratio of the two enzymes, but there is no evidence to suggest that any value within the claimed range provides for any behaviors that could be considered unexpected. That is to say, both enzymes hydrolyze their respective substrates in a normal and predictable manner. Therefore, it can be reasonably established that the claimed composition does not provide for any markedly different characteristics compared to their naturally-occurring counterparts. See MPEP 2106.04(c) and Funk Bros. Seed Co. v. Kalo Inoculant Co., 333 U.S. 127, 130, 76 USPQ 280, 281 (1948). Based upon this analysis, the claimed composition is comprised of two natural products, wherein both natural products behave as they would in isolation; both enzymes hydrolyze their respective substrates, utilizing the same predictable kinetics, as they would in isolation, assuming the presence of the appropriate substrate.
In the most recent amendments, the claims have been amended to recite “recombinant enzyme.” This limitation does not improve the eligibly of the claim under 35 USC 101. Even if a cell is created to recombinantly produce an enzyme that is not natural to it does not make the enzyme, per se, unnatural. This can be demonstrated in Association for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 591-94, 106 USPQ2d 1972, 1979-81 (2013) wherein the BRCA1 sequence, per se, was considered natural, regardless of where it was located and how it was produced or isolated. For example, if a yeast cell is engineered to produce human insulin, the insulin appears identical to human insulin and would still be considered a product of nature; this is because its direct counterpart: human insulin, is objectively identical in sequence, structure, and function. See Diamond v. Chakrabarty, 447 U.S. 303, 310, 206 USPQ 193, 197 (1980) and MPEP 2106.04(c). As such, even if an enzyme is produced recombinantly, unless the Applicant can provide evidence of objective differences between the naturally occurring enzyme, and one with the same sequence, but recombinantly produced, the claimed “recombinant enzyme” can still be considered a product of nature, since a “recombinant enzyme” includes natural enzymes that are produced in organisms that they are not natural to. Similar to the above example, if recombinantly inserting a Trichoderma reesei cellulase into a Saccharomyces cerevisiae results in a cellulase enzyme with greater activity, this would provide evidence that the claimed recombinant enzyme is markedly different than its natural counterpart. Barring evidence, a naturally occurring enzyme, regardless of how it is made, is considered the same as any other enzyme with an identical amino acid sequence.
Claim 6 provides for an additional enzyme. This claim includes the naturally-occurring class of enzymes β-glucosidase. In nature, this enzyme hydrolyzes the terminal, non-reducing, β-D-glucosyl residue of cellulose, thereby liberating the terminal β-D-glucose. When combined with the other two enzymes, this enzyme performs the same function as it would in isolation, and there is no evidence to suggest that the claimed combination of enzymes performs any unexpected actions. Each enzyme hydrolyzes the already known substrate, utilizing the same kinetics as they would in isolation, assuming the appropriate substrate is present. Therefore, the claimed consortium of enzymes would provide for the same markedly different characteristic analysis as above.
Claims 2 and 3 more specifically define the type of naturally occurring enzyme, by claiming its family designation, but there is no evidence to suggest that the claimed enzymes perform any different than they would in nature/in isolation. Claims 4, 5, and 7 further define the ratio of the enzymes to each other, but there is no evidence to suggest that any of the claimed ratios provide for unexpected changes in the composition’s behavior. Claim 8 describes a “whole fermentation broth,” which given the instant specification, can be interpreted as an aqueous solution of the claimed enzymes. Since the claimed enzymes would not be able to properly behave without an aqueous solution, this does not change the markedly different characteristic analysis.
Claim 17 is considered ineligible because the enzymes are still natural and behaving as they would in isolation. For example, the claimed glucoamylase and endoglucanase would behave identically if they were placed in isolation; both glucoamylase and endoglucanase provide for predictable substrate-product kinetics, regardless of whether they are in a composition together or apart. If there is an excess of substrate, glucoamylase in isolation, provides for the same substrate-product kinetics as it would if it was placed in a composition with endoglucanase and an excess of substrate. Both enzymes appear identical to their natural counterpart, and behave identically to their natural counterpart, with respect to kinetics and substrate-product interactions.
Claim 18 is considered eligible because the claimed enzyme, in isolation, appears identical regardless of the fact that it was produced by endogenous or exogenous genetics. There is no evidence to suggest that a recombinantly produced naturally occurring enzyme is any different than its natural counterpart.
Claim Rejections - 35 USC § 102/103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-11, 15, and 18-20 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Yazdani, et al (US Pat. 10,526,593)..Yazdani describes an enzymatic composition that is used for the generation of glucose from cellulose. See column 1, lines 6-20. Specifically, Yazdani describes a multienzyme consortium that includes glucoamylase, and endoglucanase. Yazdani provides for enzymes that are administered at the claimed ratios, wherein endoglucanase comprises 2-25% of the composition and glucoamylase provides for 8-15%. See column 4, lines 29-40. For example, a composition that is 25% endoglucanase and 15% glucoamylase provides for a fraction relative to the glucoamylase and the endoglucanase wherein REG is 0.625 (25/[25+15] = 0.625) and RGA is 0.375 (15/[25+15] = 0.375).
Although Yazdani does not state that the enzymes were recombinant, if a skilled artisan were to take a sample of Yazdani’s enzyme composition, and that claimed, it is unclear if the skilled artisan would be capable of distinguishing any differences, because a recombinantly produced natural enzyme would be expected to look and behaved the same as its natural counterpart. If the skilled artisan cannot distinguish any differences between the claimed composition and that of the prior art, the prior art must have anticipated the claimed composition (35 USC 102); additionally, if there is evidence to support the fact that the claimed composition provides for an enzyme that is different than those disclosed in Yazdani, if a substrate were placed in Yazdani’s enzyme composition, and the same substrate were placed in the claimed composition, there is a reasonable expectation that they will yield the same product, with similar kinetics, because the claimed composition would be an obvious variant of Yazdani. That is to say, the function and kinetics of the enzyme classes disclosed in Yazdani are exceptionally well-studied and highly predictable; the ordinary artisan would be wholly capable of reproducing obvious variants of Yazdani’s composition using Yazdani and knowledge generally available to the ordinary artisan. The claims composition would be included in one of these obvious variants. This is highlighted by the fact that there is no evidence to suggest that the claimed composition provides for any products or kinetics that are not already discussed in the prior art.
With respect to claim 1, Yazdani teaches the two claimed enzymes, and describes them in the same ratio to each other as that claimed.
With respect to claim 2, Yazdani teaches GH15-glucoamylase. See column 4, line 40.
With respect to claim 3, Yazdani teaches GH5-endoglucanase. See column 4, lines 29 and 30.
With respect to claims 4 and 5, Yazdani indicates that the endoglucanase comprises 2-25% of the total [protein] composition, and the glucoamylase is 8-15% of the total [protein] composition. See column 4, lines 22-42.
With respect to claims 6 and 7, Yazdani teaches the β-glucosidase GH3, provided at a range of 1-4% of the total protein content. See column 4, line 25; column 20, line 27.
With respect to claims 8, 9, and 11, Yazdani provides for several applied examples wherein the enzyme composition is exposed to a substrate to liberate glucose. See columns 13 and 14. Yazdani also explicit mentions the hydrolysis of cellulose, into glucose, using an enzymatic consortium. See column 2, lines 16-20. If it can be shown that Yazdani never intended to provide a method of glucose generation from cellulose, this method would be entirely obvious to the ordinary artisan. These steps would fulfill the claimed limitations.
With respect to claims 10 and 15, Yazdani generally describes microbial fermentation of the acquired sugars. See column 1, lines 20-25. However, Yazdani does not explicitly describe methods of fermentation. If it can be shown that there is not a clear impetus to provide the sugars of Yazdani for ethanol production, through fermentation, this method would be entirely obvious to the ordinary artisan.
With respect to claim 18, as discussed above, even if an enzyme is heterologously produced, it continues to act and appear as if the enzyme was produced in its native microbe.
With respect to claims 19 and 20, Yazdani discloses a range of endoglucanase and glucoamylase that overlaps with the claimed ratios. Based upon the ordinary artisan’s knowledge of the predictably of enzymes, and their ability to optimize ratios based upon routine testing, would suggest that these rations would be obvious if they are not explicitly disclosed in Yazdani.
Claim Rejections - 35 USC § 103
Claims 12, 17, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Yazdani, et al (US Pat. 10,526,593).
With respect to claims 12 and 21, although it is unclear if Yazdani provides for the claimed range in the above-cited applied examples, the claimed enzymes are well-known and widely used, wherein their kinetics are highly predictable. The ordinary artisan would be well-within their skills to optimize the amount of enzyme to substrate.
With respect to claim 17, Yazdani indicates that a number of microbial species produce relevant enzymes. There is nothing non-obvious about generating a consortium of enzymes produced from different microbes. Since these enzymes are well-studied, and highly predictable, this would continue to be obvious and predictable.
Claims 13 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Yazdani, et al (US Pat. 10,526,593) and Tolan, et al (US Pat 8,318,461). Although Yazdani indicates that the prior art is aware that cellulose can be pretreated prior to enzymatic hydrolysis, it is never explicitly suggested. See column 2, lines 16-19. However, when looking upon the cited patent, it is noted that Tolan teaches similar methods of hydrolyzing cellulose, into sugar, with a consortium of enzymes that are both similar to Yazdani, and those claimed. See column 1, lines 14-19; column 5, lines 62-67. As such, it would be reasonable to suggest that elements that apply to Tolan would be reasonably expected to apply to Yazdani, and vice versa. In Tolan’s background of the invention, Tolan indicates that cellulose feedstocks can be quite recalcitrant, and require pretreatment to help improve hydrolysis. These pretreatments include those claimed in claim 14. See columns 1 and 2. Since pretreatment is such a well-known, and widely used technique for improving glucose yields, it would be obvious to perform this additional methods step in the methods described/implied by Yazdani.
Conclusion
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 DAVID W BERKE-SCHLESSEL whose telephone number is (571)270-3643. The examiner can normally be reached M-F 8AM-5:30PM.
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/DAVID W BERKE-SCHLESSEL/Primary Examiner, Art Unit 1651