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 .
Applicant’s response filed 08/28/2026 has been received and considered entered. This is a response to amendments and arguments filed 08/28/2026.
Election/Restrictions
Applicant’s election of Group I (claims 1-14), SEQ ID NO:11 of Group A, and SEQ ID NO:27 of Group C in the reply filed on 07/06/2026 was acknowledged.
However, the species election requirement of Group A is withdrawn.
Claims 15-16 stand withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claim 19 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 in the reply filed on 07/06/2026.
Claims Status
Claims 2-4 is/are cancelled and claims 17-19 is/are newly added. Claims 1, 5-19 is/are currently pending with claims 15-16, 19 withdrawn. Claims 1, 5-14, 17-18 is/are under examination.
Claim Interpretation
The claims contain limitations preceded by the term “optional”. All claim limitations recited as “optional” are interpreted as not required. As such, prior art can be applied to teach these limitations, but does not need to be applied.
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, 5-6, 8 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) an enhancer (claim 1) and a nucleic acid molecule comprising an enhancer and a promoter (claims 5-6, 8), wherein the enhancers and promoters are naturally occurring. This judicial exception is not integrated into a practical application because the products of nature are not integrated into a practical application, and no additional elements are required beyond the products of nature. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claim the enhancer or the enhancer and promoter, with no additional limitation which amounts to significantly more than the naturally-occurring genetic sequences and chromosomes, nor does it meet any other considerations under MPEP 2106.05(a-h). The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception. The only elements recited in claims 1, 5-6, and 8 are enhancers and combinations of enhancers and promoters which exist in nature in naturally-occurring chromosomes.
Claims 1, 5-6, and 8 recite nucleic acid molecules, which constitute compositions—one of the statutory categories of invention.
Claims 1, 5-6, 8 recite products which encompass products of nature as described in MPEP § 2106.04(b)(II). These compositions are enhancers and combinations of enhancers and promoters which are found in nature (e.g., SEQ ID NO:11 is found in human chromosome 15; SEQ ID NOs:2 and 6 are part of the known TRMP1 gene sequence, see NCBI Reference Sequence NG_016453.2). The specification teaches that SEQ ID NOs:1-14 and 32-39 are derived from human or mouse genomes, without any additional modification or structures (Table 1). Claim 1 recites naturally occurring enhancer sequences with no additional limitations; claim 5 is drawn to an “isolated nucleic acid molecule” comprising an enhancer and a promoter, encompassing chromosomes (which are nucleic acid molecules) which naturally comprise these sequences; claim 6 is drawn to a nucleic acid molecule consisting of an enhancer linked by a spacer to a promoter, encompassing a fragment of a naturally occurring chromosome, consisting of the enhancer, the promoter, and intervening sequence (spacer) which are naturally occurring; claim 8 is drawn to an expression vector, encompassing a chromosome.
According to Step 2A, Prong Two, set forth in MPEP § 2106.04(II)(A)(2), the claims are next evaluated with respect to whether the judicial exception is integrated into a practical application. These considerations are set forth in MPEP § 2106.05(a)-(h). This analysis turns to the additional steps or elements recited within the claims. Claims 1, 5-6, and 8 do not recite any additional elements beyond what has been determined to be a judicial exception.
There are no additional elements that reflect an implementation with a particular additional element nor is it transformed or reduced to a different state, nor which meets any other considerations under MPEP § 2106.05(a)-(h), such that the claimed compositions amount to significantly more than the judicial exceptions.
For all these reasons, claims 1, 5-6, and 8 are directed to judicial exceptions without significantly more and are rejected.
Claim Rejections - 35 USC § 112
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.
Claim 17 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 17 recites that the gene comprises or consists of SEQ ID NO:46 or 47; however, SEQ ID NO:47 is an amino acid sequence. A gene is inherently a nucleic acid and not a polypeptide. It is thus unclear as to what is encompassed by the claimed sequence with respect to SEQ ID NO:47.
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 1, 5-14, 17-18 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 new ground of rejection necessitated by amendment.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V, v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the 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. See, e.g., Pfaff v. Wells Eiees., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641,1647 (1998); Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm., 927 F. 2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it”).
According to the MPEP § 2163, "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 (see i)(A) above), reduction to drawings (see i)(B) above), or by disclosure of relevant, identifying characteristics, i.e., 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 applicant was in possession of the claimed genus (see i)(C) above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutsch land GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus.")."
Claims 1 and 5 recite an enhancer that “is shown in any one of SEQ ID NO: 4-8, 10-14, 36, 38-39” and a promoter that “is shown in any one of SEQ ID NO: 1-3, 34”, respectively. This creates an enormous genus of species, as an element that “is shown in” a SEQ ID NO denotes any sequence comprised within that SEQ ID NO, including both the full length of that SEQ ID NO and any fragment of any size comprised within that SEQ ID NO.
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. In the instant case, nucleic acid sequences of SEQ ID NOs: 1-8, 10-14, 34,36, 38-39 are the only species of this genus whose complete structures are disclosed. While the genus encompasses a large number of variants and molecules that have the same activity as transcriptional regulators (enhancers and promoters) and the genus encompasses a large number of variants and molecules that have a different structure, the specification does not describe the complete structure of a representative number of species of the large genus of enhancers or promoters comprised in or having the sequence of SEQ ID NOs:1-8, 10-14, 34,36, or 38-39 or functional equivalents thereof. Additionally, the specification does not describe the complete structure of a representative number of species of the large genus of enhancers or promoters comprised in or having the sequence of SEQ ID NOs: 1-8, 10-14, 34,36, or 38-39.
Next, then, it is determined whether a representative number of species have been sufficiently described by other relevant identifying characteristics (i.e. other than nucleotide sequence), specific features and functional attributes that would distinguish different members of the claimed genus. In the instant case, the only other identifying characteristic is that the sequence “has expression specificity and sufficient expression activity in retinal ON-bipolar cells, and can be efficiently expressed in human retinal organoids, and has the potential to be used to treat human ophthalmology retinal related diseases, especially thoses retinal macular region-related diseases” (page 3 lines 3-6). Such a functional limitation cannot be an identifying characteristic for the claimed diverse genus of molecules since by Applicant’s definition of these enhancers and promoters or functional equivalent thereof, all members of the claimed genus will have that characteristic. Further, no identifying characteristics of the enhancers or promoters comprised in but not having the full-length sequence of SEQ ID NOs: 1-8, 10-14, 34,36, 38-39 are disclosed.
The inventions of claims 6-14 and 17-18 require the use of the inventions of claims 1 and 5 and therefore are likewise rejected under 35 U.S.C. 112, first paragraph, as failing to comply with the written description requirement.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claim(s) 1, 5, 8 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by NCBI Reference Sequence NG_016453.2 (2016; human chromosome 15 GRCh38 primary assembly). This is a new ground of rejection necessitated by amendment.
Regarding claims 1, 5, 8, the NCBI Reference Sequence (human TRPM1 sequence, chromosome 15) teaches a nucleic acid sequence and expression vector (chromosome) comprising instant SEQ ID NOs:2 and 6 (see alignments below).
SEQ ID NO:2:
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133
858
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SEQ ID NO:6:
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244
1300
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Claim(s) 1 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Olek (WO2003078657A1, of record). This rejection is maintained.
Regarding claim 1, Olek teaches a nucleic acid comprising SEQ ID NO:1 (SEQ ID NO:1 comprises a sequence 100% identical to instant SEQ ID NO:4, see alignment below).
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152
661
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Response to Arguments
Applicant's arguments filed 08/28/2026 have been fully considered but they are not persuasive. Applicant argues that though Olek teaches instant SEQ ID NO:4, Olek is not a proper reference under 35 USC 102 because Olek does not disclose that SEQ ID NO:1 of Olek comprises an enhancer sequence. However, as the structures are identical (SEQ ID NO:1 of Olek comprises a sequence 100% identical to instant SEQ ID NO:4), Olek does inherently teach an enhancer which meets the requirements of instant claim 1.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claim(s) 1, 5-6, 11-14, 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wyk (WO2012174674A1), in view of NCBI Reference Sequence NG_016453.2 (2014; human chromosome 15 GRCh38 primary assembly). This is a new ground of rejection necessitated by amendment.
Regarding claims 1, 5-6, 8-11, Wyk teaches a nucleic acid molecule and an rAAV vector comprising a TRPM1 enhancer/promoter combination and a sequence encoding a light-sensitive (photosensitive) transgene (claims 1, 11, 13, 15-16).
Regarding claims 12 and 14, Wyk teaches that the nucleic acid molecule is comprised in a medicament (claim 19) and used as a medicament (claims 19-20, 22).
Regarding claim 13, Wyk teaches that the medicament is used in a method of treating retinitis pigmentosa or macular degeneration (claim 22).
Regarding claim 18, Wyk teaches that the AAV is AAV2 (pages 14, 27).
However, Wyk does not teach the sequences of TRPM1 enhancers and promoters.
The NCBI Reference Sequence NG_016453.2 teaches that the 5’ UTR of hTRPM1 consists of nucleotides 64549-84918.
Regarding claims 1 and 5, the NCBI Reference Sequence teaches that the 5’ UTR of hTRPM1 consists of nucleotides 64549-84918, comprising instant SEQ ID NOs:4 and 6 (see alignments below).
SEQ ID NO:4:
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244
1289
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SEQ ID NO:6:
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244
1300
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It would have been obvious to an artisan at the time of filing that a nucleotide sequence comprising a combination of TRPM1 enhancer and promoter would include the complete sequence of the TRPM1 5’ UTR as described in the NCBI Reference Sequence for the human TRPM1 gene. As such, the nucleotide sequence rendered obvious by the combination of Wyk and the NCBI Reference Sequence would comprise instant SEQ ID NOs:4 and 6 and an intervening spacer sequence.
Double Patenting
Applicant is advised that should claim 14 be found allowable, claims 12-13 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. Claims 12 and 13 only differ from claim 14 in that these two claims recite intended uses of identical compositions to those of claim 14; however, the compositions of claims 12-14 do not differ structurally and are structurally indistinguishable. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AFRICA M MCLEOD whose telephone number is (703)756-1907. The examiner can normally be reached Mon-Fri 9:00AM-6:00PM EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ram Shukla can be reached on (571) 272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/AFRICA M MCLEOD/Examiner, Art Unit 1635
/RAM R SHUKLA/Supervisory Patent Examiner, Art Unit 1635
