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
In the Applicant’s reply, dated 5/27/2026, the Applicant has provided amendments to the claims, and arguments drawn to the previous rejections. The Applicant has not amended the specification to remove hyperlinks/browser executable code, and as such, this objection is maintained.
On page 6 of the Applicant’s Arguments, the Applicant states that claim 6 has been amended and should overcome the objection. Although the claim has been amended to be consistent with the narrower limitation provided in the claim from which it depends, the issue provided in the objection continues to be present. If the claim includes “at least 95% sequence identity,” all of the limitations that follow would necessarily be encompassed by that limitation. For example, the limitation that follows, “at least 95.5% sequence identity,” would necessarily be encompassed by the “at least 95% sequence identity” limitation. Providing limitations that describe some percentages between 95% and 100% does not improve the claim language, since the ordinary artisan wholly understands the percentages that are “at least 95%,” and the numbers that would lie between 95% and 100%.
On page 6 of the Applicant’s Arguments, the Applicant states the amended claims are now in compliance with 35 USC 112(a) Written Description, because the claimed functionality should be clear to the ordinary artisan, with respect to the claimed homology. The Applicant has provided prior art to bolster this argument. Based upon the narrowing of the limitation, and the cited prior art, the 35 USC 112(a) Written Description rejection is withdrawn.
On page 7 of the Applicant’s Arguments, the Applicant states that claim 5 is canceled and as such, the 35 USC 112(d) rejection of the claim is moot. Since the claim is canceled, the rejection is withdrawn.
On page 7 of the Applicant’s Arguments, the Applicant discusses how the recombinant sequence has improved activity over “naturally occurring DAO.” First, based upon the instant specification, it appears as though the primary structure (the sequence of amino acids) of the claimed DAO enzyme (SEQ ID NO: 1) naturally occurs in Yarrowia lipolytica, wherein the claimed enzyme only relies on its sequence to identify it. Since the claimed sequence, per se, occurs in nature, claims drawn to the sequence, per se, must be considered natural products. This analysis is consistent with the Office guidance regarding Association for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 589-91, 106 USPQ2d 1972, 1978-79 (2013). See MPEP 2106.04(b). It appears as though the Applicant is contending that modifying the Y. lipolytica genome will affect the protein folding of the DAO enzyme, wherein this affects its function in an unpredictable manner. However, based upon the claim language, this alleged improvement is not captured in the claim language, since the claim language only considers the sequence. If the manner of making the claimed product provides unexpected changes and/or improvements, the composition claims should be provided as a product-by-process limitation. This would encompass the described improvement, and provide for an invention that can longer be perceived as natural. See MPEP 2113. By providing a product-by-process limitation, the claims are no longer purely defined by the sequence, but are now drawn to how the method of making the composition affects the function in a non-natural manner.
On page 8 of the Applicant’s Arguments, the Applicant states that the recitation of “recombinant” provides for an enzyme that is different than the cited art. As was discussed above, the claims are drawn to a sequence. If the prior art describes the sequence, prefacing the claim with “recombinant” does not change the fact that the sequence, per se, is known. If the sequence is anticipated, the claim is anticipated. If, as discussed above, the manner of making the enzyme provides for unexpected changes, the claim should be described using product-by-process language. Based upon the Applicant’s arguments, it appears as though amending the composition in terms of how it is made, would likely eliminate the cited prior art. Finally, since the claims were rejected under 35 USC 102 and 103, the Applicant has not made reasonable arguments as to why it would not be obvious to the ordinary artisan to recombinantly make a known and useful enzyme using art accepted techniques that would be obvious and well-known to the ordinary artisan.
On pages 8 and 9 of the Applicant’s Arguments, the Applicant argues that there is no clear teaching that the cited prior art describing cheese that was made with Y. lipolytica has “DAO enzyme falling within the scope of the present claims.” To the contrary, the present claims continue to read upon cheese that was made with Y. lipolytica as the present claims only require that the sequence is administered, there is no requirement that the enzyme be extracted, purified, manufactured recombinantly, or anything other than natural production from Y. lipolytica. Since the prior art establishes that Y. lipolytica produces DAO, and some cheeses contain Y. lipolytica, then the consumption of these cheeses that contain Y. lipolytica would necessarily fulfill the claim limitation. This is because there would be a reasonable expectation that if a DAO-producing microbe are present for the fermentation of the cheese, the DAO-producing microbe would have been expected to produced DAO; if DAO is produced in cheese, then the method of “preventing” would have necessarily been accomplished, because the enzyme was present in a step of administering. The Applicant has provided no evidence to assert that this is an incorrect assessment of the prior art.
On pages 8 and 9 of the Applicant’s Arguments, the Applicant contends that the prior art does not teach administering recombinant enzymes or isolated enzymes (with respect to the 35 USC 103 rejection of claims 10-12). There are no limitations drawn to the administration of recombinant enzymes or isolated enzymes. As such, these elements are immaterial to the claims and rejection.
The Applicant has amended independent claims, which has required a reanalysis of the claims, and the prior art. Based upon the amendments, all of the previous 35 USC 102/103 rejections will be strictly 35 USC 103 rejections. These obviousness rejections are supported by the newly added IDS references Missbichler, et al (PGPub 2008/0193491 [IDS Reference]) and Underberg, et al (US Pat. 4,725,540 [IDS Reference]). Currently, all 35 USC 112(a) and (d) rejections are withdrawn. The objection to the specification is maintained. The previous 35 USC 101 rejections are maintained for the reasons previously provided as well as those discussed in the response, above. No claim is allowed.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claim 6 is objected to because of the following informalities: the claim does not need to list every value above “at least 72%,” since it would be exceptionally clear to the ordinary artisan that “at least 72%” would include all of the values that follow. Appropriate correction is required.
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, and 4 are rejected under 35 U.S.C. 101 because the claimed invention is directed to product of nature without significantly more. The claim(s) recite(s) SEQ ID No 1, which is a naturally occurring enzyme found in Yarrowia lipolytica P01f. This judicial exception is not integrated into a practical application because the claims provide for the sequence/enzyme, per se, but do not provide for any additional ingredients that would change the nature of the claimed enzyme.
The Applicant is directed to MPEP 2106 for the analysis of the claims under 35 USC 101, especially the flow chart found in section III. Since the claims are drawn to a composition, the claims provide for a statutory category, and as such, the answer to step 1 is “yes.” The second step asks if the claims are directed to a product of nature; since the claims are drawn to an enzyme that is naturally found in Y. lipolytica, the answer to step 2A is “yes.” In addition to the instant specification describing this enzyme as being isolated from a naturally occurring yeast, and is not engineered, the IDS reference Nunez, et al (Encyclopedia of Dairy Sciences, 2nd Edition, Elsevier, Boston, 2011 [IDS Reference]) indicates that this enzyme is naturally found in Y. lipilytica and wherein the yeast can be isolated from cheese. See page 452, right column, first [incomplete] paragraph. Based upon this, it is clear that the yeast strain and the enzyme are products of nature. The next step requires the Examiner to perform a markedly different characteristic analysis. See MPEP 2106.04(c). Claim 1 provides for a “functional food,” and claim 4 provides for the enzyme, per se. When considering claim 1, there is no evidence to suggest that the claimed diamine oxidase provides for any unexpected behaviors or kinetics other than the predicted diamine oxidase activity, even when in contact with a food product.
It must also be considered that the claims provide for an isolated enzyme. Based upon guidance regarding Association for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 591-94, 106 USPQ2d 1972, 1979-81 (2013), even though the claimed enzyme is isolated, which provides for “hand of man,” the enzyme is identical to its natural counterpart, and provides for identical diamine oxidase behaviors, regardless of it being inside or outside the yeast cell. Since both the “function food” and enzyme, per se, would provide for diamine oxidase activity that is identical to that of the natural counterpart, the claimed compositions must be considered products of nature.
Claim Rejections - 35 USC §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, 3, 4 and 6-15 are rejected under 35 U.S.C. 103 as being unpatentable over Nunez, et al (Encyclopedia of Dairy Sciences, 2nd Edition, Elsevier, Boston, 2011 [IDS Reference]) Missbichler, et al (PGPub 2008/0193491 [IDS Reference]) and Underberg, et al (US Pat. 4,725,540 [IDS Reference]). Nunez teaches that the yeast Y. lipolyitica has been isolated from certain cheeses, wherein Y. lipolytica naturally produces the enzyme diamine oxidase. See page 452, right column 1st [incomplete] paragraph. Although Nunez does not provide for any sequence data, based upon an assessment from the instant specification, it seems like the enzyme of the claims provides for the same behaviors as the enzyme described in Nunes. As such, it would be reasonable to suggest that the Y. lipolytica enzyme disclosed in Nunez, wherein this enzyme possesses diamine oxidase activity, is the same as the Y. lipolytica enzyme claimed.
Although Nunez teaches a composition that would be expected to include naturally occurring diamine oxidase, there is no motivation to generate a recombinant form of the enzyme. Both Missbichler and Underberg teach compositions and methods of using diamine oxidase to treat foods and prevent certain diseases. See Missbichler, column 3, lines 29-36; Underberg, paragraph [0026] [0027]. Underberg notes that diamine oxidase can be manufactured recombinantly. See paragraph [0043]. Based upon these two references, it is clear that the ordinary artisan already knows the utility of adding diamine oxidase to foods and using these compositions to prevent certain disorders; furthermore, the prior art suggests that it would be obvious to the ordinary artisan to recombinantly generate the enzyme, since recombinant methods are well-known to the ordinary artisan as a means of producing cellular products, like enzymes. However, since neither reference teaches the sequence of the described diamine oxidase, there is no manner to accurately determine if the prior art is describing the same enzyme as that claimed, or if the claimed enzyme is an obvious variant of the cited prior art. Since there is no explicit mention of sequence, it will be assumed that the claimed sequence provides for an obvious variant of the enzymes described.
With respect to claim 1, Nunez provides for Y. lipolytica diamine oxidase, and cheese. Nunez notes that the cheese includes decarboxylated amino acids, thereby confirming diamine oxidase activity. See page 452, right column, 1st [incomplete] paragraph. Y. lipolytica provides for the claimed enzyme with [an assumed] 100% homology. Underberg motivates the ordinary artisan to manufacture the enzyme recombinantly.
With respect to claims 3, 6 and 7, the cheese described in Nunez appears to provide for the claimed method. That is to say, the cheese is the claimed “biogenic amine-containing product,” and Y. lipolytica provides for the claimed enzyme with [an assumed] 100% homology. However, there is ample motivation found in both Missbichler and Underberg to treat food with diamine oxidase enzymes/
With respect to claim 4, Nunez describes the diamine oxidase enzyme that is found in Y. lipolytica, and as such, appears to anticipate the claim. If it can be shown that the enzyme is not that claimed. Since the enzyme has a clear utility in the art, it would be obvious to manufacture this enzyme recombinantly.
With respect to claims 8 and 9, as discussed above, Nunez teaches that the enzyme is found in Y. lipolytica, which is found in cheese. As such, Nunez teaches the claimed enzyme in cheese. Even still, Missbichler and Underberg motivate the ordinary artisan to apply the enzyme to other foods.
With respect to claims 13-15, Nunez teaches the claimed biogenic amines, and indicates that they act as substrates to diamine oxidase enzymes. See page 452, Table 1.
Claim Rejections - 35 USC § 103
Claims 10-12 are rejected under 35 U.S.C. 103 as being unpatentable over Nunez, et al (Encyclopedia of Dairy Sciences, 2nd Edition, Elsevier, Boston, 2011 [IDS Reference]) and Izquierdo-Casas, et al (Clinical Nutrition, 38, 152-158, 2019). See the discussion of Nunez above. Although Nunez appears to describe the claimed enzyme, there is nothing in the cited prior art that suggests using the enzyme in a method for treating or preventing a disease/condition related to a buildup of biogenic amines.
Izquierdo-Casas teaches methods of treating migraine headaches with diamine oxidase supplementation; Izquierdo-Casas notes that these headaches are related to a buildup of the biogenic amine - histamine. See page 152, “Summary” section. Although it is unclear what the origin of the diamine oxidase enzyme is, it seems reasonably clear that as long as the enzyme exhibits diamine oxidase activity, it should predictably provide for the same outcomes as those disclosed in Izquierdo-Casas. As such, even if Izquierdo-Casas does not teach the claimed enzyme source, or teaches an enzyme with a different sequence, it would continue to be obvious to the ordinary artisan that all diamine oxidases, regardless of source and sequence, would be expected to behave identically to others defined as “diamine oxidases.” This class of enzymes behave predictably, and the ordinary artisan would understand the subtle differences in kinetics between sources. The claimed method appears to be an obvious variant of Izquierdo-Casas, wherein the instant method uses an obvious variant enzyme, as compared to Izquierdo-Casas.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Tams, et al (PGPub 2013/0084358).
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.
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, Melenie Gordon can be reached at 571-272-8037. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DAVID W BERKE-SCHLESSEL/Primary Examiner, Art Unit 1651
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