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 claims benefit of priority to Japan Application No. JP2020-198419 filed 11/30/2020. This application is also a 371 of PCT/JP2021/043758 filed 11/30/2021. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. However, an English translation of the foreign patent document was not provided. Therefore, for the purposes of applying prior art, the effective filing date of the claimed invention is 11/30/2021.
Amendments and Claim Status
In the reply filed 05/26/2026, Applicant amended claims 18, 33 and 36.
Claims 17-36 are currently pending.
Claims 17, 19-32 and 34-35 remain withdrawn by the Examiner.
Claims 18, 33 and 36 are under examination.
Maintained Objections (with modification as necessitated by amendment)
Specification Objections
The disclosure is objected to because of the following informalities: The Specification still recites bacterial genus/species without being italicized. Applicant has amended the Specification to italicize some recitations of bacterial genus/species. However, non-italicized recitations remain. For example, see paragraph [0010] of the amended Specification filed 05/26/2026.
Appropriate correction is required.
Claim Objections
Claim 33 is objected to because of the following informalities: Claim 33 is missing the word ‘to’ in line 4 after the recitation of ‘D-allulose.’ The claim as-amended recites “contacting the protein of Claim 18 with D-allulose isomerize” in lines 3-4. The claim should recite “contacting the protein of claim 18 with D-allulose to isomerize …”.
Claim 33 is also objected to because the ‘C’ in ‘Claim 18’ in both lines 3 and 7 is capitalized.
Appropriate correction is required.
Maintained Rejections (with modification as necessitated by amendment)
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.
Claim 18 is rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim does not fall within at least one of the four categories of patent eligible subject matter because the claims are directed to a product of nature.
STEP 1: Is the claim to a process, machine, manufacture or composition of matter?
Answer to STEP 1: Yes, claim 18 is directed to a protein, a product.
STEP 2: Is the claim directed to a law of nature, a natural phenomenon or an abstract idea
(judicially recognized exceptions)?
Step 2 comprises two, respective steps: Step 2A Prong 1 and Step 2A Prong 2.
STEP 2A, PRONG 1: Does the claim recite an abstract idea, law of nature or natural
phenomenon?
A claimed product is ‘directed to’ a natural phenomenon if the product of the claim is not
‘markedly different’ from its closest-occurring natural counterpart.
With regard to STEP 2A, PRONG 1:
The invention of claim 18 is a protein having the amino acid sequence of instant SEQ ID NO: 1. This amino acid sequence, according to a preponderance of evidence, is a naturally occurring amino acid sequence. Specifically, according to the instant Specification, instant SEQ ID NO: 1 is from Enterobacter roggenkampii NrT7-1 (Specification, Paragraph [0057]).
Thus, as there is no evidence the sequence is artificial in any way, the amino acid sequence encoding the protein of claim 18 is interpreted as a naturally-occurring amino acid sequence. Considering the amino acid sequence is naturally-occurring, there is no difference in the protein as claimed and the protein as it occurs in nature. Therefore, when compared to its closest naturally occurring counterpart, which is the naturally occurring protein in Enterobacter roggenkampii NrT7-1, there is no difference between the amino acid sequence of the protein as claimed and the naturally occurring counterpart in Enterobacter roggenkampii NrT7-1.
Even though the protein was isolated from a microorganism, being Enterobacter roggenkampii NrT7-1, as evidenced by the instant Specification (Specification, Paragraph [0038]), isolating is not demonstrative of a marked difference between the natural amino acid encoding the protein as there is nothing present within the claim which specifically focuses on any chemical changes due to isolating the protein from its natural habitat, the microorganism Enterobacter roggenkampii NrT7-1.
It is noted claim 18 has been amended to recite the protein is immobilized on a carrier that enables a continuous isomerization reaction. There is no indication in the Specification that immobilizing the protein on carrier results in the protein have any characteristics that are different from the naturally occurring protein in its natural state. That is, the carrier simply immobilizes the protein, the carrier itself is not responsible for the continuous isomerization reaction. Rather, an additional protein, being an enzyme, is required for the isomerization reaction to occur. The protein and the carrier alone do not react in a manner that provides a continuous isomerization reaction. Thus, the claimed protein does not have markedly different characteristics from what occurs in nature.
Answer to STEP 2A, PRONG 1: Yes, the claim is directed to a natural product (‘natural phenomenon’).
STEP 2A, PRONG 2: Does the claim recite additional elements that integrate the natural product into a practical application?
Integration into a practical application” according to the most recent PEG guidance:
1. Requires an additional element or a combination of additional elements in the claim to apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception, such that the claim is more than a drafting effort designed to monopolize the exception.
2. Uses the considerations laid out by the Supreme Court and the Federal Circuit to evaluate whether the judicial exception is integrated into a practical application.
With regard to STEP 2A, PRONG 2:
The only additional element is the carrier that the protein is immobilized on. Although the limitation indicates the protein is immobilized on the carrier, it does not provide any information as to how the protein is immobilized and recites a carrier in high generality. While the carrier must be an ion exchange resin, sodium alginate or a synthetic adsorbent, these are all generic carriers that fail to meaningfully limit the claim because it is at best the equivalent of merely adding the words “apply it” to the judicial exception because the protein and the carrier alone do not interact in such a way that amounts to a markedly different product. The carrier simply immobilizes the protein so that the protein can be used in combination with another protein for a continuous isomerization reaction. However, the combination of the protein and the carrier alone does not provide for a continuous isomerization reaction.
ANSWER TO STEP 2A, PRONG 2: No, the claim does not recite additional elements that integrate the JE into a practical application.
ANSWER TO STEP 2A: Yes, the claim is directed to a Judicial Exception.
STEP 2B: Does the claim recite additional elements that amount to significantly more than the JE?
The only additional element is the carrier that the protein is immobilized on. However, the protein being immobilized on a carrier is well-understood, routine and conventional activity in the scientific community. For example, Iyappan et al. (Of Record), who disclose the use of rhamnose isomerase in a process to produce rare monosaccharides such as psicose and allose (See entire document, Abstract), immobilize rhamnose isomerase in their conversion reaction (Column 3, Lines 38-40). Moreover, Iyappan et al. immobilize the rhamnose isomerase with sodium alginate (Column 5, Lines 5-7). Additionally, the claim recites the carrier in such a high level of generality that it merely tells a scientist to utilize any ion exchange resin, sodium alginate or synthetic adsorbent.
ANSWER TO STEP 2B: No, the claim does not recite any additional elements that amount to significantly more than the Judicial Exception.
For the foregoing reasons, claim 18 is rejected under 35 U.S.C. § 101 for being directed to non-eligible subject matter because the claim merely identifies an amino acid encoding a protein which is naturally-occurring, a Judicial Exception which is not markedly different from its naturally-occurring counterpart and does not recite additional elements which integrate the natural product into a practical application or contribute significantly more than the Judicial Exception itself.
Status of the Art
Claims 18 and 33 as-amended appear to be free of the prior art. The closest prior art regarding the protein of claim 18, which is also required by claim 33, is A0A4R0FYS9_ENTR disclosed by UniProt (UniProt, 07/31/2019) (IDS Reference of 05/30/2023, 1 Page). UniProt discloses A0A4R0FYS9_ENTR, an L-rhamnose isomerase, which shares 99.1% sequence identity to instant SEQ ID NO: 1. An alignment is provided below wherein Qy is instant SEQ ID NO: 1 and Db is A0A4R0FYS9_ENTR disclosed by UniProt.
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However, A0A4R0FYS9_ENTR disclosed by UniProt does not share the sequence of instant SEQ ID NO: 1 nor would it be obvious to one of ordinary skill in the art to modify A0A4R0FYS9_ENTR disclosed by UniProt at the specific amino acid positions or to the specific amino acids where instant SEQ ID NO: 1 and A0A4R0FYS9_ENTR differ. Thus, claim 18 appears to be free of the prior art. Similarly, claim 33 requires the protein of claim 18. Therefore, claim 33 also appears to be free of the prior art.
However, claim 18 is still not allowable as it is rejected under 35 U.S.C. 101 as set forth above. Additionally, claim 33 is not allowable as it currently objected to. Claim 33 would also require amendment to become allowable as it recites “the protein of claim 18” and claim 18 is currently rejected under 35 U.S.C. 101.
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.
Claim 36 is rejected under 35 U.S.C. 103 as being unpatentable over Iyappan et al. (US 9752170 B2, 09/05/2017) in view of UniProt (A0A4R0FYS9_9ENTR, 07/31/2019) (IDS Reference of 05/30/2023, 1 Page).
Regarding claim 36, Iyappan et al. disclose a gene encoding rhamnose isomerase and the use of the rhamnose isomerase in a process to produce rare monosaccharides such as psicose and allose (See entire document, Abstract). More specifically, Iyappan et al. disclose:
A process of overproduction of rare monosaccharides from fructose, said process comprising the steps of:
1. culturing host cells transformed with an expression construct comprising SEQ ID NO:1 and SEQ ID NO:2 in a separate suitable medium in the presence of IPTG or lactose for a period in the range of 2-3 hours to produce D-tagatose 3-epimerase and rhamnose isomerase respectively,
2. isolating the expressed protein from the host cells by conventional method, and purifying the isolated protein using chromatographic techniques,
3. immobilizing D-tagatose 3-epimerase and rhamnose isomerase thus produced in the previous step in a suitable matrix,
4. contacting fructose with immobilized D-tagatose 3-epimerase for a period in the range of 5 to 10 hours to produce psicose, and
5. contacting D-psicose produced in the previous step with immobilized rhamnose isomerase for a period in the range of 6-12 hours to produce D-allose (Claim 13 of Iyappan et al.).
Thus, Iyappan et al. disclose a method of producing D-allose, the elected species of what is produced, comprising contacting rhamnose isomerase with D-psicose to produce D-allose. It is noted D-psicose is another name for D-allulose.
Iyappan et al. do not disclose the rhamnose isomerase has 90% sequence identity to instant SEQ ID NO: 1.
However, UniProt discloses A0A4R0FYS9_9ENTR, an L-rhamnose isomerase, with gene name rhaA from Enterobacter wuhouensis (Page 1). A0A4R0FYS9_9ENTR from UniProt shares 99.1% sequence identity to instant SEQ ID NO: 1. A sequence alignment is provided below wherein Qy represents instant SEQ ID NO: 1 and Db represents A0A4R0FYS9_9ENTR of UniProt.
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While UniProt does not disclose the specific activity indicated in part (A) or (B) of the claim, it appears, absent evidence to the contrary, the protein disclosed by UniProt would necessarily provide the claimed activity as it is also an L-rhamnose isomerase that falls within the limitations set forth in (b). Therefore, it appears the claimed activity is inherent to the protein and the protein disclosed by UniProt would necessarily provide the claimed activity.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized the L-rhamnose isomerase disclosed by UniProt in the method of Iyappan et al. as it amounts to simple substitution of one known element for another because the L-rhamnose isomerase was a known L-rhamnose isomerase. Therefore, it would have been obvious to one of ordinary skill in the art to utilize the L-rhamnose isomerase disclosed by UniProt motivated by the desire to effectively produce D-allose. Exemplary rationales that may support a conclusion of obviousness include simple substitution of one known element for another to obtain predictable results. See MPEP 2143(I)(B).
USC § 103 – Response to Arguments
Applicant's arguments filed 05/26/2026 have been fully considered but they are not persuasive.
Applicant argued it is unpredictable to rely on generic rhamnose isomerase annotation as a basis for substitution and that there is evidence there is substantial divergence between the rhamnose isomerase of Iyappan and A0A4R0FYS9 (Page 17). Applicant further argued Iyappan does not teach or disclose a protein with the sequence of instant SEQ ID NO: 1 nor does Iyappan disclose a protein with 90% sequence identity to instant SEQ ID NO: 1 (Page 17).
The Examiner respectfully disagrees. It is the Examiner’s position that it is common to rely on well-known and utilized databases, such as UniProt, to identity proteins and their functions. While every single protein may not provide the annotated function, one of ordinary skill in the art would have a reasonable expectation that a protein within a well-known and utilized database would provide the function it is annotated to provide as the function is inferred based upon sequence homology to other proteins that provide such function. Thus, it remains the Examiner’s position that it would be obvious to utilize another protein annotated as an L-rhamnose isomerase in the method of Iyappan, including A0A4R0FYS9_9ENTR as recited in the modified rejection set forth above, as it amounts to simple substitution of one known element for another to obtain predictable results. See MPEP 2143(I)(B).
Conclusion
No claims are allowed.
Claims 18 and 36 are rejected.
Claim 33 is objected to.
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.
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/A.T.W./Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
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