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
This application is a National-Stage entry (371) of PCT/IL2022/050690, filed 6/27/22, which claims benefit of priority to U.S. Provisional Patent Application No. 63/215,472, filed on 6/27/2021. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Election/Restrictions
Applicant’s election of Group I (claims 1-4 and 18), in the reply filed on 6/3/2026 is acknowledged. Further, Applicant’s election of SEQ ID NO: 11 as the elected species of the polypeptide is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election(s) has been treated as an election without traverse (MPEP § 818.01(a)).
The requirement is still deemed proper and is therefore made FINAL.
Applicant’s amendment to the claims filed 6/3/2026 is acknowledged. This listing of the claims replaces all prior versions and listings of the claims.
After entry of the amendment, claims 1, 4-6, 9-10, 13, 15, 17, 26-27, 31-33, and 35-39 are pending. Claims 38 and 39 are newly added.
Claims 5-6, 9-10, 13, 15, 17, 26-27, 31-33, and 35-37 are herein withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse.
Claims 1, 4, 18, 38, and 39 are pending and were examined on the merits.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 9/25/2024 and 11/19/2025 are acknowledged. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are 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 (see e.g. [0124]; [0125]; [0129]; [0200] of the specification filed 12/27/2023).
Specification
The disclosure is objected to because of the following informalities:
TRADE NAMES, TRADEMARKS, AND OTHER MARKS USED IN COMMERCE:
The use of the terms SEPHAROSE™ (registered by CYTIVA BIOPROCESS, appears in [0044]-[0046] and [0217]); and TWEEN™-20 (see [0203]); which are each a trade name or a mark used in commerce, has been noted in this application. Note that this list is not comprehensive, and Applicant’s attention to ensuring that all trademarks are other marks used in commerce are properly identified is requested.
The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks (see MPEP 608.01(v) and 608.01(u)).
Appropriate correction is required.
Claim Interpretation
Claim 1 is being interpreted under the Broadest Reasonable Interpretation (B.R.I.), in light of the specification, as claiming any D-psicose 3-epimerase (E.C. 5.1.3.30) enzymes having at least 88% sequence identity to the amino acid sequence of SEQ ID NO: 11; 88% sequence identity to the sequence of SEQ ID NO: 12; or 92% sequence identity to the sequence of SEQ ID NO: 13. These enzymes catalyze the conversion of D-fructose to D-psicose by catalyzing epimerization at the C3 position (see [0090]-[0091] of the specification).
For claim 4, the claim recites “the polypeptide comprises an amino acid sequence selected from SEQ ID NOs: 11, 12, and 13”. This has been interpreted under the B.R.I. in view of the specification as limiting the polypeptide to one comprising a sequence that is 100% identical to the sequence of SEQ ID NO: 11, 12, or 13. Because the claim is comprising, the entire sequence of one of these must be present, however it is still open-ended as to other amino acids which may be present (e.g. a N-terminus or C-terminus tag).
Under the B.R.I., claim 18 is found to require one of the polypeptides of claim 1 and an acceptable carrier, which can include (as indicated in the specification). All of the language following “optionally” is not required of the claim. The specification (at [0153]) defines “acceptable carrier” as a non-toxic, inert, solid, semi-solid or liquid filler, diluent, encapsulating material, formulation auxiliary of any type, or simply a sterile aqueous medium, such as saline. This is found to include water, aqueous solutions, and any of the other examples found in [0153] of the specification.
For claims 38 and 39, the claims are limited to only the polypeptide sequence comprising at least 88% identity or 100% identity to SEQ ID NO:11, respectively.
Claim Rejections - 35 USC § 112(b)
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.
Claims 1, 4, 18 and 38-39 are 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 1 as presented recites:
“1. (Currently Amended) A polypeptide comprising an amino acid sequence selected from the group consisting of:
(i) SEQ ID Nos: 11-12 or a functional analog having at least 88% sequence identity thereto; and
(ii) SEQ ID No: 13, or a functional analog having at least 92% sequence identity thereto; and wherein said polypeptide is characterized by having a D-psicose 3-epimerase activity.”
The resulting claim is indefinite because the limitation “; and wherein said polypeptide is characterized by having a D-psicose 3-epimerase activity” has been presented with option (ii). Thus, it is unclear to one reading the resulting claim if this limitation is only to be part of option “(ii)” or if it applies to both “(i)” and “(ii)”. All of the claimed sequences appear to have D-psicose 3-epimerase, but due to the formatting and the use of “; and” twice in the body of the claim, the claim could be interpreted either way in terms of the application of the wherein clause. Correction is recommended. For clarity, is suggested to move the wherein clause to a new line or to before the presentation of options (i) and (ii).
All other claims depend directly or indirectly from the rejected claims and are also rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, for the reasons set forth above.
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.
For determining subject matter eligibility, the following analysis was considered, per MPEP § 2106.
Patent Eligibility Analysis Step 1: Step 1 of the eligibility analysis asks: is the claim to a process, machine, manufacture or composition of matter? Yes, the claims are directed to a composition. (Claims 1, 18, and 38, STEP 1: YES).
Patent Eligibility Analysis Step 2A Prong 1: Step 2A, prong 1 asks: does the claim recite an abstract idea, law of nature, or a natural phenomenon (product of nature)?
Claims 1, 18, and 38 each encompass any D-psicose 3-epimerase (E.C. 5.1.3.30) enzymes, comprising a polypeptide having an amino acid sequence which is at least 88% identical to the sequence of SEQ ID NO: 11.
SEQ ID NO: 11 appears to be derived from a naturally occurring sequence from Ornithinimicrobium pratense (as demonstrated in UniProt Entry A0A5J6V7K4; UniProt [online], entry version 7, “Sugar phosphate isomerase/epimerase”, XP093272951, 7 April 2021, cited on IDS filed 11/19/2025).
Thus, the B.R.I. of the claims include limitations encompassing natural products specifically, the claims encompass the polypeptide sequence of A0A5J6V7K4 from Ornithinimicrobium pratense. This sequence has been found to be 93.7% similar to the sequence recited in SEQ ID NO: 11. Thus the claims recite a nature-based product, and include the enzyme with an identical sequence to the natural enzyme.
When a claim recites a nature-based product limitation, the markedly different characteristics (MDC) analysis is used to determine whether the natural product has markedly different characteristics from its natural counterpart (see MPEP 2106.04(c)). MPEP § 2106.04(c) explains “Where the claim is to a nature-based product produced by combining multiple components, the markedly different characteristics analysis should be applied to the resultant nature-based combination, rather than its component parts.”
In this case, the appropriate natural counterpart for the polypeptide of claims 1, 18, and 38 would be the natural occurring epimerase from Ornithinimicrobium pratense having the sequence set forth in A0A5J6V7K4.
The second step in the MDC analysis is to identify appropriate characteristics to compare. Appropriate characteristics can be expressed as the nature-based product’s structure, function, and/or other properties, and are evaluated on a case-by-case basis. In this case, the appropriate characteristics include the sequence, the structure of the enzyme, and the function. The final step in the markedly different characteristics analysis is to compare the characteristics of the claimed nature-based product to its naturally-occurring counterpart in its natural state, in order to determine whether the characteristics of the claimed product are markedly different. The courts have emphasized that to show a marked difference, a characteristic must be changed as compared to nature, and cannot be an inherent or innate characteristic of the naturally-occurring counterpart or an incidental change in a characteristic of the naturally occurring counterpart. Myriad, 569 U.S. at 580, 106 USPQ2d at 1974-75. Thus, in order to be markedly different, the inventor must have caused the claimed product to possess at least one characteristic that is different from that of the counterpart (MPEP § 2016.04(c).II.C.). If there is no change in any characteristic, the claimed product lacks markedly different characteristics, and is a product of nature exception.
No characteristics of the naturally-derived enzyme are markedly changed by isolation or purification. Further, the production of this enzyme synthetically or recombinantly still results in an polypeptide that is essentially identical to that of the naturally-occurring enzyme.
When considered as a whole composition, there is no evidence or suggestion that the claimed product has any markedly different structure of function than the naturally occurring polypeptide, which falls within the claimed scope by its amino acid sequence.
Therefore, the claimed product lacks markedly different characteristics, and is a product of nature exception (Claims, 1, 18, and 38, Step 2A, Prong 1: YES).
Patent Eligibility Analysis Step 2A Prong 2: Step 2A, prong 2 asks: does the claim recite additional elements that integrate the judicial exception into a practical application?
Claims 1 and 38 do not recite any additional elements other than the product of nature exception, and its sequence homology requirements (e.g. the structure). Claim 38 does recite that the polypeptide is isolated or synthetic, however the naturally occurring enzyme remains encompassed by this claim. There is no claimed difference between the isolated or synthetic polypeptide and the naturally occurring one.
Claim 18 further recites that the enzyme is part of a composition having a suitable carrier. As previously discussed, an “acceptable carrier” is defined in the instant application as a non-toxic, inert, solid, semi-solid or liquid filler, diluent, encapsulating material, formulation auxiliary of any type, or simply a sterile aqueous medium, such as saline and includes water, and other natural solutions (see [0153] of the specification). Thus, the claim encompasses naturally occurring carriers and the naturally occurring enzyme.
Please note that combining natural products such as the instantly claimed enzyme with another natural product such as water, cellulose, or alginate, does not remove the claims from reading upon a judicial selection (Funk Brothers Seed Col. V. Kalo Inoclulant Col. – 333 U.S. 127 (1948)) because again there is no evidence of a marked difference brought about by combining the instantly claimed natural products. An enzyme is found in nature in an aqueous environment, namely the intracellular or extracellular environment in which it is used.
Please also note that modifying the concentration of the product in such a composition has been also found not sufficient to remove the claimed composition from a judicial exception (see, e.g., Association for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576 (2013)).
There is no practical application or implementation of the natural product recited.
Therefore, the judicial exception is not integrated into a practical application because the claims do not recite any additional elements other than the naturally-occurring product(s) and innate functional characteristics thereof (Claims 1, 18, and 38, Step 2A, Prong 2: NO).
Patent Eligibility Analysis Step 2B: Does the claim recite additional elements that amount to significantly more than the judicial exception?
The recitation of an innate property or characteristic of a naturally occurring enzyme (e.g. the epimerase activity) does not result in significantly more than the judicial exception. Claim 1 encompasses the naturally occurring enzyme without significantly more
Claim 18 recites the additional element of a carrier, but not does not amount to significantly more than a combination of naturally occurring products, including the instantly claimed enzyme in any suitable aqueous environment (e.g. cytoplasm, saline solution, water).
Claim 38 also recites that the polypeptide is either isolated or synthetically produced, but this does not amount to significantly more than the ineligible natural product. The claim reads on a nature-derived product, which lacks markedly distinct characteristics from the naturally occurring counterpart. A synthetic product which is otherwise identical to a natural product remains ineligible, as discussed in MPEP § 2106.04(c).II.C.2, describing Myriad, wherein “the Supreme Court made clear that not all changes in characteristics will rise to the level of a marked difference, e.g., the incidental changes resulting from isolation of a gene sequence are not enough to make the isolated gene markedly different. Myriad, 569 U.S. at 580, 106 USPQ2d at 1974-75.” See also “Ambry Genetics, 774 F.3d at 760-61, 113 USPQ2d at 1244. In sum, because the characteristics of the claimed primers were innate to naturally occurring DNA, they lacked markedly different characteristics from nature and were thus product of nature exceptions”. Similarly, the instantly claimed enzyme is not found markedly distinct from that of the natural one, regardless of how it is obtained.
When considered as a whole, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception (Claims 1, 18, and 38, Step 2B: NO).
As such, the claims do not qualify as eligible subject matter. For these reasons, claims 1, 18, and 38 are rejected under 35 U.S.C. § 101 as being directed to non-statutory subject matter.
Claims 4 and 39 are found to limit the claims to variants of the epimerase polypeptides that are not found in nature. Thus these particular sequences are not natural products.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1 and 38 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by A0A5J6V7K4 (UniProt [online], entry version 7, “Sugar phosphate isomerase/epimerase”, XP093272951, 7 April 2021, cited on IDS filed 11/19/2025).
A0A5J6V7K4 discloses an epimerase from Ornithinimicrobium pratense that is approximately 93.7% similar to the sequence of SEQ ID NO:11 (see included alignment at the end of this action). Because this sequence has greater than 88% identity to the claimed sequence, and is recognized as an epimerase, it is deemed to anticipate the claimed polypeptide, defined by its structural features as being at least 88% similar to SEQ ID NO:11.
MPEP § 2112.01 states that for product and composition claims: “Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).” In this case, the reference discloses a polypeptide sequence that fulfills all of the structural requirements presented. Predictably, such an enzyme would innately have the same functional activity as the polypeptides which are so instantly claimed.
Both claims 1 and 38 are considered to be anticipated by this database entry, corresponding to a naturally occurring enzyme which has an amino acid sequence which is encompassed by the instant claims.
Claim Rejections - 35 USC § 103
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claims 1, 18, and 38 are rejected under 35 U.S.C. 103 as being unpatentable over Lanos et al. (US PGPub No. 20160281076) in view of A0A5J6V7K4 (UniProt [online], entry version 7, “Sugar phosphate isomerase/epimerase”, 7 April 2021, on IDS filed 11/19/2025).
Lanos et al. pertains to an improved variants of a D-psicose 3-epimerase (DPEase) and its uses (Abstract, Title). Lanos teaches that D-psicose, also called D-allulose, exists in extremely small quantities in commercial carbohydrate or agricultural products and is difficult to chemically synthesize, and suggests that conversion of D-fructose to D-psicose by epimerization using D-tagatose 3-epimerase (DTEase) family enzymes is an attractive and viable way of D-psicose production ([0005]). Lanos teaches methods for optimizing parent D-psicose 3-epimerases and using D-psicose as the substrate ([0011] ; [0040]-[0047]). Lanos also teaches D-psicose 3-epimerases known to the art at that time ([0056]). Lanos also teaches that the DPEase can be immobilized on any suitable support or carrier, such as alginate or resins ([0066]).
However, Lanos does not explicitly teach a sequence having at least 88% sequence identity to the claimed polypeptide (e.g. SEQ ID NO: 11, as elected).
UniProt Entry A0A5J6V7K4 discloses an epimerase from Ornithinimicrobium pratense that is approximately 93.7% similar to the sequence of SEQ ID NO:11 (see included alignment at the end of this action). This sequence, falling within the structural similarity requirements of the instant claims is predicted via its structure to have epimerase activity.
To one of ordinary skill in the art, before the effective filing date of the instant invention, it would have been prima facie obvious in view of the combined teachings of Lanos et al. and A0A5J6V7K4 to provide a sequence of the epimerase from Ornithinimicrobium pratense, which overlaps substantially with the claimed sequence SEQ ID: 11.
One would have been motivated to do so because Lanos teaches beneficial industrial uses of D-picose-3-epimerases. Because of its similar sequence and structure to known epimerases, the sequence of UniProt A0A5J6V7K4 would predictably have the desired 3-psicose D-epimerase activity. To one of ordinary skill, it would have been a matter of judicious selection and routine optimization to provide a known epimerase when performing this conversion. This amounts to a matter of simply substituting one element for another which predictably has the same function or activity, as described in MPEP § 2143.I.B- KSR Rationale B.
Claim 18 would have been obvious because Lanos teaches using alginate or resins as carriers for containing the D-psicose 3-epimerase, and alginate is considered a carrier which falls within the description provided in the instant disclosure. Based upon the teachings of Lanos, one having ordinary skill in the art would be aware of suitable solvents and carriers for enzymes and would have been motivated to provide D-psicose 3-epimerase in a useful way known to the art.
There would have been a reasonable expectation of success because Lanos teaches that D-psicose 3-epimerases can be used to produce D-psicose/D-allulose in vitro and UniProt Entry A0A5J6V7K4 teaches a related sequence having predicted epimerase activity.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date, as evidenced by the references, especially in the absence of evidence to the contrary.
Citation of Pertinent Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Venkitasubramanian et al. (US PGPub No. 20180112244) pertains to proteins that exhibit fructose to allulose epimerase activity that are useful for the industrial production of allulose from fructose (Abstract, Title). Venkitasubramanian teaches the bio-conversion of D-fructose to D-allulose by D-tagatose-3-epimerase (DT3E) or by D-psicose-3-epimerase is established in the art ([0003]; FIG. 1, FIG. 2). Venkitasubramanian teaches D-psicose-3-epimerase enzymes that have the desired activity ([0146]; [0194]; [0233]).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDREW TERRY MOEHLMAN whose telephone number is (571)270-0990. The examiner can normally be reached M-F 9am-5pm EST.
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, Anand Desai can be reached at 571-272-0947. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/A.T.M./Examiner, Art Unit 1655
/ANAND U DESAI/Supervisory Patent Examiner, Art Unit 1655
Appendix A: SEQ ID NO: 11 and Sugar phosphate isomerase/epimerase from Ornithinimicrobium pratense
PNG
media_image1.png
200
400
media_image1.png
Greyscale
Prosecution Insights