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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on April 2, 2026 has been entered.
DETAILED ACTION
The amendment filed April 2, 2026 in response to the Office Action of January 8, 2026 is acknowledged and has been entered.
Claims 9-11, 18 and 23 have been amended.
Claims 39 and 40 have been added.
Claims 9-11, and 18-40 are pending.
Claims 24-37 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions or species, there being no allowable generic or linking claim.
Claims 9-11, 18-23 and 38-40 are currently under consideration as drawn to the elected invention.
In view of claim 10 amendment, the 112(b) rejection for claim 10 set forth in previous Office Action of January 8, 2026 is hereby withdrawn.
In view of claim 10 amendment, the 112(a) rejection for claim 10 set forth in previous Office Action of January 8, 2026 is hereby withdrawn.
In view of claim 10 amendment, the 103 rejection set forth in previous Office Action of January 8, 2026 is hereby withdrawn.
Information Disclosure Statement
The Information Disclosure Statement filed on 06/02/2026 has been considered and entered by examiner.
MAINTAINED/MODIFIED REJECTIONS
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 9, 11, and 18-23 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 9 recites “a biologically active variant retinol dehydrogenase protein, wherein the variant protein consists of SEQ ID NO: 30” which is ambiguous. This claim can be interpreted as the claimed nucleic acid that encode the biologically active variant RDH protein wherein the biologically active variant RDH protein consists of SEQ ID NO: 30, or nucleic acids encoding biologically active variants of SEQ ID NO: 30.
Claim 9 recites the limitation "the variant retinol dehydrogenase" in lines 4 and 5. There is insufficient antecedent basis for this limitation in the claim.
Claim 9 recites “wherein the N-terminal transmembrane alpha helix is deleted from the variant retinol dehydrogenase” which renders the claim indefinite. The amino acid sequences of SEQ ID NO: 30 and wild-type RDH12 are shown below:
>SEQ ID NO: 30
MAGGVCRTNVQLPGKVVVITGANTGIGKETARELASRGARVYIACRDVLKGESAASEIRVDTKNSQVLVRKLDLSDTKSIRAFAEGFLAEEKQLHILINNAGVMMCPYSKTADGFETHLGVNHLGHFLLTYLLLERLKVSAPARVVNVSSVAHHIGKIPFHDLQSEKRYSRGFAYCHSKLANVLFTRELAKRLQGTGVTTYAVHPGVVRSELVRHSSLLCLLWRLFSPFVKTAREGAQTSLHCALAEGLEPLSGKYFSDCKRTWVSPRARNNKTAERLWNVSCELLGIRWE
>RDH12
MLVTLGLLTSFFSFLYMVAPSIRKFFAGGVCRTNVQLPGKVVVITGANTGIGKETARELASRGARVYIACRDVLKGESAASEIRVDTKNSQVLVRKLDLSDTKSIRAFAEGFLAEEKQLHILINNAGVMMCPYSKTADGFETHLGVNHLGHFLLTYLLLERLKVSAPARVVNVSSVAHHIGKIPFHDLQSEKRYSRGFAYCHSKLANVLFTRELAKRLQGTGVTTYAVHPGVVRSELVRHSSLLCLLWRLFSPFVKTAREGAQTSLHCALAEGLEPLSGKYFSDCKRTWVSPRARNNKTAERLWNVSCELLGIRWE
Compared with wild-type RDH12 protein, SEQ ID NO: 30 (the variant protein) already has a 25-amino acid deletion (underlined amino acids). It is unclear whether “the N-terminal transmembrane alpha helix deletion” is an additional deletion from the SEQ ID NO: 30.
Claim 11 recites “wherein the nucleic acid encodes a variant retinol dehydrogenase 12 protein, wherein the protein consists of SEQ ID NO: 30” which is ambiguous. This claim can be interpreted as the variant retinol dehydrogenase 12 protein consists of SEQ ID NO: 30, or the nucleic acid encoding variants of protein consisting of SEQ ID NO: 30. Given Broadest Reasonable Interpretation (BRI), nucleic acids encoding variants of SEQ ID NO: 30 (without N-terminal transmembrane alpha helix) are encompassed by claim 11.
Claim 11 recites “wherein the N-terminal transmembrane alpha helix is deleted from the variant retinol dehydrogenase” which is ambiguous. As set forth above, compared with wild-type RDH12 protein, SEQ ID NO: 30 (the variant RDH12 protein) already has a 25-amino acid deletion. It is unclear whether “the N-terminal transmembrane alpha helix deletion” is an additional deletion from the SEQ ID NO: 30.
Claim 11 recites the limitation "the variant retinol dehydrogenase" in lines 6 and 7. There is insufficient antecedent basis for this limitation in the claim.
Claim 23 recites “consisting of SEQ ID NO: 30, wherein the N-terminal transmembrane alpha helix is deleted from the variant retinol dehydrogenase” which is ambiguous. As set forth above, compared with wild-type RDH12 protein, SEQ ID NO: 30 (the variant RDH12 protein) already has a 25-amino acid deletion. It is unclear whether “the N-terminal transmembrane alpha helix deletion” is an additional deletion from the SEQ ID NO: 30.
Claim 23 recites the limitation "the variant retinol dehydrogenase" in lines 3 and 4. There is insufficient antecedent basis for this limitation in the claim.
Claims 18-22 are also rejected because these claims depend on the rejected claims directly or indirectly.
Response to Arguments
For the 112(b) rejection, Applicant argues: the amendments (e.g. consists of SEQ ID NO: 30) on claims 9 and 23 make the claims definite. Applicant’s arguments have been fully considered but they are not persuasive. As set forth above, the rejected claims are still ambitious, because the claims can be interpreted as the claimed nucleic acid that encode the biologically active variant RDH protein wherein the biologically active variant RDH protein consists of SEQ ID NO: 30, or nucleic acids encoding biologically active variants of SEQ ID NO: 30. Thus, the rejection is maintained for the reasons of record. In addition, the limitation: consisting of SEQ ID NO: 30 and the N-terminal transmembrane alpha helix is deleted from the variant retinol dehydrogenase is also ambiguous. It is unclear whether “the N-terminal transmembrane alpha helix deletion” is an additional deletion from the SEQ ID NO: 30.
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 9, 11, and 18-22 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 claim(s) contains 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a WRITTEN DESCRIPTION rejection.
Claim 9 is drawn a nucleic acid encoding a biologically active variant retinol dehydrogenase 12 protein, wherein the variant protein consists of SEQ ID NO: 30, wherein the N-terminal transmembrane alpha helix is deleted from the variant retinol dehydrogenase and the solubility of the variant retinol dehydrogenase is increased over the wild-type retinol dehydrogenase. Although claim 9 recites SEQ ID NO: 30, however, given BRI, as set forth above it encompass genes encoding biologically active variants of SEQ ID NO: 30. As evidenced by paragraph [0020] of the instant publication US 2022/0340949 A1 : “the encoded human RDH12 protein can also encompass sequences comprising about 80, 85, 90, 95, 96, 97, 98, 99% sequence identity to SEQ ID NO: 30”. The genus of genes that encode protein at least 80% identical to SEQ ID NO: 30, which is 291 amino acid long, is over 10116 (1058 ways to pick 58 positions from 291 possible positions and 20 options for each picked position). Thus, the claim would encompass a broad genus of variants of SEQ ID NO: 30. Similarly, claim 11 would encompass variants of SEQ ID NO: 30.
Vas-Gath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991), makes clear that: "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Gath at page 1116.)
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, disclosure of drawings, or by disclosure of relevant identifying characteristics, for example, 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 the
Applicants were in possession of the claimed genus.
The specification teaches SEQ ID NO: 30 which is a truncated human RDH12 protein without the N-terminal transmembrane alpha helix domain ([0066], [0099] and Example 1). Lee (Lee et al., Biotechnology and Bioengineering, 119(2): 399-410, Publication Date: 12/11/2024, in IDS of 10/24/2022) teaches expressing full length human RDH12 to make retinol.
The specification and prior art do not: provide any other variants which comprise about 80, 85, 90, 95, 96, 97, 98, or 99% sequence identity to SEQ ID NO: 30 and have required activity, e.g. converting retinal to retinol; produce or test any other variants in any practical application; provide any discussion on the structure-functional relationship between all possible variants; provide any evidence that the variants of RDH12 have increased solubility of any of the RDH proteins compared to wild type. Thus, one of ordinary skill in the art would not be able to readily recognize/visualize which variants would retain/gain the functions required for a practical application.
Regarding RDH12, Sarkar (Sarkar et al., Experimental Eye Research, 188 (2019) 107793, Publication Date: 09/07/2019) teaches that due to the difficulty in expression and purification of RDHs, the structure of RDH12 or that of any other vertebrate RDH has not yet been solved (page 3, col. 1, para. 3). In addition, even a single amino acid change (Y226C) in RDH12 can lead to loss of enzyme activity (page 1, col. 2, para. 1).
In view of above, other than the truncated RDH12 (SEQ ID NO: 30), one of ordinary skilled in the art would not be able to readily recognize/visualize any other variants of truncated RDH12 protein, wherein the N-terminal transmembrane alpha helix is deleted, with required biochemical properties for a practical application.
Furthermore, the written description provision of 35 USC § 112 is severable from its enablement provision; and adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993). And Amgen Inc. v. Chugai
Pharmaceutical Co. Ltd., 18 USPQ2d 1016. The Guidelines for Examination of Patent
Applications under the 35 USC §112 paragraph 1, "Revision 1" of Written Description
Requirement (66 FR 1099-1111, March 25, 2008) state, "[p]ossession may be shown in a variety of ways including description of an actual reduction to practice, or by showing the invention was 'ready for patenting' such as by disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the Applicant was in possession of the claimed invention (Id. At 1104). Moreover, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. However, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; nor has Applicant shown the invention was "ready for patenting" by disclosure of drawings or structural chemical formulas that show that the invention was complete; nor has the
Applicant described distinguishing identifying characteristics sufficient to show that
Applicant were in possession of the claimed invention at the time the application was filed.
Claims 11, 18-22 also encompass a broad genus of variants of SEQ ID NO: 30 as claim 9.
Therefore for all these reasons the specification lacks adequate written description, and one of skill in the art cannot reasonably conclude that Applicant had possession of the claimed invention at the time the instant application was filed.
Response to Arguments
For the 112(a) rejection, Applicant argues:
Applicants have amended claim 9 to recite that a nucleic acid encodes a biologically active variant retinol dehydrogenase 12 enzyme consisting of SEQ ID NO:30. Claims 10-11 and 18 (and claims 19-22) depend from claim 9 and thus carry the same limitations. Claim 23 has also been amended as claim 9. As amended, Applicants submit that the claims are supported by the description of the specification.
Applicant’s arguments have been fully considered but they are not persuasive. As set forth above, given BRI, the claims still encompass variants of SEQ ID NO: 30. The specification and prior art does not provide sufficient written description support for the broad genus of variants of SEQ ID NO: 30 which have the required properties as claimed, e.g. increased solubility, maintained enzyme activity. Thus, the rejection is maintained for the reasons of record.
NEW REJECTIONS
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 10 and 39 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 10, which depends on claim 9, recites the nucleic acid sequence is selected from the group consisting of SEQ ID NO: 18 and SEQ ID NO: 20. Claim 9 recites a nucleic acid encoding a protein consists of SEQ ID NO: 30. However, the encoded protein of SEQ ID NO: 18 does not comprise full-length of SEQ ID NO: 30, and the encoded protein of SEQ ID NO: 20 comprises additional amino acids compared with SEQ ID NO: 30, as shown below:
>SEQ ID NO:18_translated (290 amino acids in length)
AGGVCRTNVQLPGKVVVITGANTGIGKETARELASRGARVYIACRDVLKGESAASEIRVDTKNSQVLVRKLDLSDTKSIRAFAEGFLAEEKQLHILINNAGVMMCPYSKTADGFETHLGVNHLGHFLLTYLLLERLKVSAPARVVNVSSVAHHIGKIPFHDLQSEKRYSRGFAYCHSKLANVLFTRELAKRLQGTGVTTYAVHPGVVRSELVRHSSLLCLLWRLFSPFVKTAREGAQTSLHCALAEGLEPLSGKYFSDCKRTWVSPRARNNKTAERLWNVSCELLGIRWE
>SEQ ID NO: 20_translated (303 amino acids in length)
MAGGVCRTNVQLPGKVVVITGANTGIGKETARELASRGARVYIACRDVLKGESAASEIRVDTKNSQVLVRKLDLSDTKSIRAFAEGFLAEEKQLHILINNAGVMMCPYSKTADGFETHLGVNHLGHFLLTYLLLERLKVSAPARVVNVSSVAHHIGKIPFHDLQSEKRYSRGFAYCHSKLANVLFTRELAKRLQGTGVTTYAVHPGVVRSELVRHSSLLCLLWRLFSPFVKTAREGAQTSLHCALAEGLEPLSGKYFSDCKRTWVSPRARNNKTAERLWNVSCELLGIRWELTAALEHHHHHH
>SEQ ID NO: 30 (291 amino acids in length)
MAGGVCRTNVQLPGKVVVITGANTGIGKETARELASRGARVYIACRDVLKGESAASEIRVDTKNSQVLVRKLDLSDTKSIRAFAEGFLAEEKQLHILINNAGVMMCPYSKTADGFETHLGVNHLGHFLLTYLLLERLKVSAPARVVNVSSVAHHIGKIPFHDLQSEKRYSRGFAYCHSKLANVLFTRELAKRLQGTGVTTYAVHPGVVRSELVRHSSLLCLLWRLFSPFVKTAREGAQTSLHCALAEGLEPLSGKYFSDCKRTWVSPRARNNKTAERLWNVSCELLGIRWE
The protein encoded by SEQ ID NO: 18 or SEQ ID NO: 20 does not meet the limitation “consists of SEQ ID NO: 30”. Thus, claim 10 fails to include all the limitations of claim 9.
Similarly, Claim 39 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 39, which depends on claim 38, recites the nucleic acid sequence is selected from the group consisting of SEQ ID NO: 18 and SEQ ID NO: 20. Claim 38 recites a variant biologically active RDH consisting of SEQ ID NO: 30. As set forth above, claim 39 fails to include all the limitations of claim 38.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Section 33(a) of the America Invents Act reads as follows:
Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.
Claim 40 is rejected under 35 U.S.C. 101 and section 33(a) of the America Invents Act as being directed to or encompassing a human organism. See also Animals - Patentability, 1077 Off. Gaz. Pat. Office 24 (April 21, 1987) (indicating that human organisms are excluded from the scope of patentable subject matter under 35 U.S.C. 101). Although the specification describes results of expressing the variant RDH in microorganisms (see Examples), claim 40 does not limit the term “an organism”. Thus, given Broadest Reasonable Interpretation (BRI), the claim would encompass humans expressing the variant retinol dehydrogenase. Thus, claim 40 is rejected 35 U.S.C. 101 and section 33(a) of the America Invents Act.
Conclusion
Claims 38 is drawn to allowable subject matter.
Claims 9-11, 18-23, 39 and 40 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHENG LU whose telephone number is (571)272-0334. The examiner can normally be reached Monday-Friday 8-5.
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/CHENG LU/ Examiner, Art Unit 1642
/PETER J REDDIG/Primary Examiner, Art Unit 1646
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