DETAILED ACTION
Applicant’s response filed June 29, 2026 has been received and entered into the application file. Applicant’s arguments and amendments to the claims have been fully considered.
Claims 16-22, 24-29, 32-33, and 36-38 of the claim set filed June 29, 2026 are pending. Claims 1-15, 23, 30-31 and 34-35 are cancelled. Of the pending claims, claims 21-22, 24-29, 32-33, and 37-38 are withdrawn. Thus, claims 16-20 and 36 are being examined on the merits herein.
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 .
OBJECTION(S)/REJECTION(S) WITHDRAWN
Nucleotide and/or Amino Acid Sequence Disclosures
RE: Specific deficiencies and the required response to this Office Action are as follows:
(1) Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). All sequences longer than ten nucleotides or four amino acids referenced in the specification must include a SEQ ID NO and must be included in the Sequence Listing. MPEP 2422.02 requires, "that when a sequence is presented in a drawing, regardless of the format or the manner of presentation of that sequence in the drawing, the sequence must still be included in the Sequence Listing and the sequence identifier ("SEQ ID NO:X') must be used, either in the drawing or in the Brief Description of the Drawings." See MPEP § 2421-2422.
Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
See Fig T2 which has amino acid or nucleic acid sequences that are not accompanied by SEQ ID NO in the figure or in the specification.
Applicant submitted a substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings. Thus, the previously filed objection is withdrawn.
Drawings
Re: The drawings of May 19, 2023, and specifically Fig T2, are objected to because the drawings contain nucleotide and amino acid sequences that are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
Applicant amended the Brief Description of the Drawings section of the specification describing Fig 22 (formerly Fig T2) to insert the sequence identifiers corresponding to the sequences listing in Fig 22. As such, the previous objection is withdrawn.
RE: The drawings are objected to because the drawings are not numbered in consecutive Arabic numerals, as required by 37 C.F.R § 1.84 (u)(1). In the instant case, the drawings are numbered as Fig. 1-6, Fig. S1-S14 and Fig. T1-T2. Examiner respectfully notes the Figures should be labeled consecutively as Fig. 1-22, for example.
Applicant submitted replacement sheets of the drawings with the figures amended so that all of the figures are labeled using consecutive Arabic numerals: Figs 1-22. The specification is amended throughout to renumber said figures. As such, the previously filed objection is withdrawn.
RE: The drawings are objected to because p20/38-22/38 of the drawings are not labeled as any particular figure. Examiner believes p20/38-22/38 are unlabeled duplicates of Fig. S14 found on p23/38-25/38.
Applicant amendment deleted p20/38-22/38. As such, the previously filed objection is withdrawn.
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.
RE: Claim 31 is 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.
Applicant amendment cancelled claim 31, thus making the rejection of said claim moot.
OBJECTION(S)/REJECTION(S) MAINTAINED & UPDATED FOR AMENDMENT
Claim Interpretation
&
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.
RE: Claims 16-20, 23, 30-31 and 36 are rejected under 35 U.S.C. 112(b), 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. Dependent claims 17-20, 23, 30-31 and 36 are rejected by virtue of their dependency on claim 16 and for not remedying the issue at hand.
Applicant amendment cancelled claims 23 and 30-31, thus making the rejection of said claims moot.
Applicant amended claim 16 to state:
A kit of parts having biological activity, the kit of parts comprising
- a first target comprising a first protein,
- a second target, coupled to comprising a liposome, exosome, DNA, RNA, viral protein, transcription factor, or small molecule,
wherein the first protein and the second protein are suitable to form a heterodimer upon irradiation with ultraviolet (UV), visible or infrared light in a first wavelength range or in the dark, which can
wherein the biological activity consists of triggering both the uptake of DNA, RNA, proteins, or small molecules into a cell, and biological effects, and
wherein at least one of the first and the second target itself has reduced biological activity as compared with the heterodimer,
wherein the first protein is a phytochrome and the second protein is a phytochrome interacting partner or vice versa,
wherein the phytochrome is selected from the group consisting of PhyA, PhyB, PhyC, PhyD, PhyE, BphP1 and DrBphP and the phytochrome interacting partner is selected from the group consisting of PIF1, PIF2, PIF3, PIF4, PIF5, PIF6, PIF7, PIF8, FHY1, FHL, PpsR2, Q- PAS1 and engineered antibodies.
Thus, in essence, claim 16 can be re-phrased/reads on as stating:
A kit of parts having biological activity, the kit of parts comprising
- a first target (not clearly defined) comprising a first protein wherein the first protein is a phytochrome and wherein the phytochrome is selected from the group consisting of PhyA, PhyB, PhyC, PhyD, PhyE, BphP1 and DrBphP,
- a second target (not clearly defined) comprising a liposome, exosome, DNA, RNA, viral protein, transcription factor, or small molecule (one way in which to read the claim- the 2nd target comprises the molecules), coupled to a second protein wherein the second protein is a phytochrome interacting partner and the phytochrome interacting partner is selected from the group consisting of PIF1, PIF2, PIF3, PIF4, PIF5, PIF6, PIF7, PIF8, FHY1, FHL, PpsR2, Q- PAS1 and engineered antibodies,
wherein the first protein and the second protein are suitable to form a heterodimer upon irradiation with ultraviolet (UV), visible or infrared light in a first wavelength range or in the dark, which can be reversed upon irradiating the heterodimer with UV, visible or infrared light in a second wavelength range or in the dark, wherein the second wavelength range is different from the first wavelength range (functional language taken into account for examination purposes),
wherein the biological activity (intended use of the kit) consists of triggering both the uptake of DNA, RNA, proteins, or small molecules into a cell (cell is not positively recited as being required by the kit), and biological effects, and
wherein at least one of the first and the second target itself has reduced biological activity as compared with the heterodimer (functional language).
Thus, said kit is for the use of light-controlled importing of DNA, RNA and/or proteins into cells but said cells are not a required limitation of said kit.
In regards to the previously filed rejection, Applicant’s amendment removed the term “optionally” from the phrase “which can optionally be reversed upon irradiating the heterodimer with UV, visible, or infrared light in a second wavelength or in the dark, wherein the second wavelength range is different from the first wavelength range”. Thus, the phrase now states “which can be reversed upon irradiating the heterodimer with UV, visible, or infrared light in a second wavelength or in the dark, wherein the second wavelength range is different from the first wavelength range” and is therefore a required limitation of claim 16.
In regards to the previously filed rejection in which Examiner noted the claim language “a first target comprising a first protein” and “a second target comprising a second protein” is unclear and indefinite, Applicant amended to define “a first protein” as wherein the first protein is a phytochrome and wherein the phytochrome is selected from the group consisting of PhyA, PhyB, PhyC, PhyD, PhyE, BphP1 and DrBphP and further amended to define “a second protein” as wherein the second protein is a phytochrome interacting partner and the phytochrome interacting partner is selected from the group consisting of PIF1, PIF2, PIF3, PIF4, PIF5, PIF6, PIF7, PIF8, FHY1, FHL, PpsR2, Q- PAS1 and engineered antibodies. Further, Applicant amended to define the second target/protein as comprising a liposome, exosome, DNA, RNA, viral protein, transcription factor, or small molecule, and as being coupled to a second protein.
Thus, Applicant has clearly defined the first protein and the second protein. However, Examiner respectfully notes a specific structural element is not defined as being required by the “first target” and the “second target” in claim 16.
Per the claims, the first target is defined by claim 19 as being suitable to bind to a receptor or part thereof and is exemplified in Fig 1 as being DARPin. Examiner notes the language of claim 19 is an intended use of the first target and not a specific structural element. Per the claims, the second target is defined by withdrawn claim 37 as comprising a virus or a derivative thereof and is exemplified in Fig 1 as being OptoAAV. However, Examiner respectfully notes the metes and bounds of claim 16 are still unclear in regards to the specific structural elements required by the phrases “first target” and “second target”. As an example, the language of claim 19 reads on such molecular molecules as hormones. Thus, it is unclear if a hormone, for example, would be a suitable molecule for the first target.
Moreover, Examiner respectfully notes the amendment “a second target, coupled to a second protein, comprising a liposome, exosome, DNA, RNA, viral protein, transcription factor, or small molecule” is unclear. It is not clear whether it is the second target which comprises the liposome, etc or whether it is the second protein which comprises the liposome, etc. In the interest of compact prosecution, Examiner is interpreting said amendment to be read as “a second target comprising a liposome, exosome, DNA, RNA, viral protein, transcription factor, or small molecule, coupled to a second protein”. I.e., it is the 2nd target which comprises the molecules and not the 2nd protein.
Thus, as noted in the previously filed non-final and discussed supra, Examiner respectfully notes the claim language “a first target comprising a first protein” and “a second target comprising a second protein” is unclear and indefinite. It is unclear what structural element is required by the “first target” and the “second target”.
The terms “first target” and “second target” are not defined by the claims, the specification does not provide a standard for ascertaining what structure is required for said targets, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Thus, the metes and bounds of the claim cannot be determined and the claim is indefinite. Thus, the previously filed rejection is maintained and updated below for amendment.
Claims 16-20 and 36 are rejected under 35 U.S.C. 112(b), 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. Dependent claims 17-20, 23, 30-31 and 36 are rejected by virtue of their dependency on claim 16 and for not remedying the issue at hand.
As noted supra, amended claim 16 can be re-phrased/reads on as stating:
A kit of parts having biological activity, the kit of parts comprising
- a first target (not clearly defined) comprising a first protein wherein the first protein is a phytochrome and wherein the phytochrome is selected from the group consisting of PhyA, PhyB, PhyC, PhyD, PhyE, BphP1 and DrBphP,
- a second target (not clearly defined) comprising a liposome, exosome, DNA, RNA, viral protein, transcription factor, or small molecule, coupled to a second protein wherein the second protein is a phytochrome interacting partner and the phytochrome interacting partner is selected from the group consisting of PIF1, PIF2, PIF3, PIF4, PIF5, PIF6, PIF7, PIF8, FHY1, FHL, PpsR2, Q- PAS1 and engineered antibodies,
wherein the first protein and the second protein are suitable to form a heterodimer upon irradiation with ultraviolet (UV), visible or infrared light in a first wavelength range or in the dark, which can be reversed upon irradiating the heterodimer with UV, visible or infrared light in a second wavelength range or in the dark, wherein the second wavelength range is different from the first wavelength range (functional language taken into account for examination purposes),
wherein the biological activity (intended use of the kit) consists of triggering both the uptake of DNA, RNA, proteins, or small molecules into a cell (cell is not positively recited as being required by the kit), and biological effects, and
wherein at least one of the first and the second target itself has reduced biological activity as compared with the heterodimer (functional language).
Thus, said kit is for the use of light-controlled importing of DNA, RNA and/or proteins into cells but said cells are not a required limitation of said kit.
Examiner respectfully notes a specific structural element is not defined as being required by the “first target” and the “second target” in amended claim 16.
Per the claims, the first target is defined by claim 19 as being suitable to bind to a receptor or part thereof and is exemplified in Fig 1 as being DARPin. Per the claims, the second target is defined by claim 37 as comprising a virus or a derivative thereof and is exemplified in Fig 1 as being OptoAAV. However, Examiner respectfully notes the metes and bounds of claim 16 are still unclear in regards to the specific structural elements required by the phrases “first target” and “second target”. As an example, the language of claim 19 reads on such molecular molecules as hormones. Thus, it is unclear if a hormone, for example, would be a suitable molecule for the first target.
Moreover, Examiner respectfully notes the amendment “a second target, coupled to a second protein, comprising a liposome, exosome, DNA, RNA, viral protein, transcription factor, or small molecule” is unclear. It is not clear whether it is the second target which comprises the liposome, etc or whether it is the second protein which comprises the liposome, etc. In the interest of compact prosecution, Examiner is interpreting said amendment to be read as “a second target comprising a liposome, exosome, DNA, RNA, viral protein, transcription factor, or small molecule, coupled to a second protein”.
Thus, as discussed supra, Examiner respectfully notes the claim language “a first target comprising a first protein” and “a second target comprising a second protein” is unclear and indefinite. It is unclear what structural element is required by the “first target” and the “second target”.
The terms “first target” and “second target” are not defined by the claims, the specification does not provide a standard for ascertaining what structure is required for said targets, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Thus, the metes and bounds of the claim cannot be determined and the claim is indefinite. Thus, the claims (both independent claim 16 and dependent claims 17-20 and 36) are properly rejected.
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.
Re: Claims 16-20, 23, 30-31 and 36 are rejected under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter.
Applicant amendment cancelled claims 23 and 30-31, thus making the rejection of said claims moot.
Applicant amended claim 16 to specify that the first protein is a phytochrome (selected from the grouping of phytochromes listed in claim 16) and the second protein is a phytochrome interacting partner (selected from the grouping of phytochrome interacting partners listed in claim 16). Claim 16 is also amended to specify that the second target is coupled to the second protein and also comprises a liposome, exosome, DNA, RNA, viral protein, transcription factor, or small molecule, while still being able to from a heterodimer with the first protein.
Applicant’s remarks state such a fusion protein, as is now defined by amended claim 16, is not a naturally occurring composition. Examiner respectfully notes a fusion protein is not required by the claim language as currently written. The claim language “coupled to” does not limit the claim to a fusion protein. Examiner respectfully notes that the individual molecules of amended claim 16 are all still naturally occurring products. Further, and as noted supra in regards to the 112b rejection, it is still unclear as to what exactly is required by the first target and the second target in terms of structure. As currently written, claim 16 recites a generic 1st target and a generic 2nd target. Thus, Examiner respectfully notes, and as noted in Applicant remarks, amended claim 16 reads on a phytochrome as the first protein (i.e., a naturally occurring protein) and a phytochrome interacting partner as the second protein (i.e., a naturally occurring protein). Per applicant’s remarks in regards to amended claim 16 and the 101 rejections, the second protein is now required to be “coupled to” a liposome, exosome, DNA, RNA, viral protein, transcription factor, or small molecule (i.e., naturally occurring products).
Thus, amended claim 16 recites naturally occurring products, both individually, and in combination. The combination of said products, i.e., a phytochrome as the first protein and a phytochrome interacting partner as the second protein, wherein the second protein is now required to be coupled to a liposome, exosome, DNA, RNA, viral protein, transcription factor, or small molecule, does not improve or change in any way each components natural functioning. Thus, the claimed composition does not have markedly different characteristic from what occurs in nature and is a "product of nature" exception. Further, given the claims are directed to a composition, the claims do not recite additional steps that integrate the judicial exception into a practical application. Thus, in view of the above and considered as a whole, the claimed composition does not have markedly different characteristics from what occurs in nature and such elements discussed above are not significantly more than the indicated judicial exceptions. Thus, the claims do not qualify as eligible subject matter, and thus the previously filed rejection is maintained and updated below for amendment.
Claims 16-20 and 36 are rejected under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter.
The rationale set forth below conforms to current Office practice for examination of claims under § 101.
These claims are analyzed for eligibility in accordance with their broadest reasonable interpretation. All of the claims are directed to a statutory category, e.g., a composition (Step 1: YES).
The next part of the analysis involves whether the claimed invention recites or is directed to one or more judicial exceptions (Step 2A, prong one).
Claim 16: Claim 16 is directed to a biological composition comprising:
- a first target (not clearly defined) comprising a first protein wherein the first protein is a phytochrome and wherein the phytochrome is selected from the group consisting of PhyA, PhyB, PhyC, PhyD, PhyE, BphP1 and DrBphP (i.e., naturally occurring products),
- a second target (not clearly defined) comprising a liposome, exosome, DNA, RNA, viral protein, transcription factor, or small molecule (i.e., naturally occurring products), coupled to a second protein wherein the second protein is a phytochrome interacting partner and the phytochrome interacting partner is selected from the group consisting of PIF1, PIF2, PIF3, PIF4, PIF5, PIF6, PIF7, PIF8, FHY1, FHL, PpsR2, Q- PAS1 and engineered antibodies (i.e., naturally occurring products),
wherein the first protein and the second protein are suitable to form a heterodimer upon irradiation with ultraviolet (UV), visible or infrared light in a first wavelength range or in the dark, which can be reversed upon irradiating the heterodimer with UV, visible or infrared light in a second wavelength range or in the dark, wherein the second wavelength range is different from the first wavelength range (functional language taken into account for examination purposes),
wherein the biological activity (intended use) consists of triggering both the uptake of DNA, RNA, proteins, or small molecules into a cell (cell is not positively recited as being required by the claim), and biological effects, and
wherein at least one of the first and the second target itself has reduced biological activity as compared with the heterodimer (functional language).
Claim 16 is recited in a generic manner in terms of the 1st target and 2nd target. Claim 16 does not define a structural element required by the 1st target or the 2nd target. Thus, given its broadest reasonable interpretation, claim 16 would encompass a composition comprising (1) a phytochrome such as PhyB (i.e., as a 1st protein) and (2) a small molecule (i.e., generically recited, reads on a naturally occurring structure) coupled to a phytochrome interacting partner such as PIF6 (i.e., as a 2nd protein). Examiner notes “coupled to” reads on annealed, aggregated, covalently bound, etc. Thus, claim 16 recites a combination of naturally occurring products.
Further, Examiner additionally notes PhyB (i.e., 1st protein) and PIF6 (i.e., 2nd protein) form a heterodimer upon irradiation with UV, visible or infrared light, as is required by amended claim 16.
In regards to the limitation directed to biological activity, the claim language as currently written is not narrowed to the proteins disclosed as having said biological activity. The claim language as currently written does not exclude other naturally occurring elements providing said biological activity.
The claim as a whole, considering all claim elements both individually and in combination, does not amount to significantly more than natural products. The combination of said natural products does not improve or change in any way each components natural functioning. Thus, the claimed composition does not have markedly different characteristic from what occurs in nature and is a "product of nature" exception. Accordingly, the claim is directed to an exception (Step 2A, prong one: YES). Thus, the claims do not qualify as eligible subject matter, and are rejected under 35 U.S.C. 101.
Claim 17: Claim 17 depends from claim 16. Claim 16, as currently written, does not require a cell. Thus, claim 17 does not modify the original structure of the claimed proteins of claim 16. Thus, the combination of a cell to the naturally occurring proteins of claim 16 does not improve or change in any way each components natural functioning. Thus, the claimed composition does not have markedly different characteristics from what occurs in nature and is a "product of nature" exception. Accordingly, the claim is directed to an exception (Step 2A, prong one: YES). Thus, the claims do not qualify as eligible subject matter, and are rejected under 35 U.S.C. 101.
Claims 18-20: It is noted that these claims recite limitations that are considered only to be directed to intended use/functional limitations. Said limitations do not modify the original structure of the claimed proteins and further the recited function of the claims do not provide additional structure/do not structurally modify the composition to provide a markedly different characteristic. Thus, the claimed composition does not have markedly different characteristics from what occurs in nature and is a "product of nature" exception. Accordingly, the claims are directed to an exception (Step 2A, prong one: YES). Thus, the claims do not qualify as eligible subject matter, and are rejected under 35 U.S.C. 101.
Claim 36: Said claim is related to naturally occurring products which do not modify the original structure of the claimed proteins in such a way that is markedly different from what occurs in nature. The combination does not improve or change in any way each components natural functioning. Thus, the claimed composition does not have markedly different characteristic from what occurs in nature and is a "product of nature" exception. Accordingly, the claim is directed to an exception (Step 2A, prong one: YES). Thus, the claims do not qualify as eligible subject matter, and are rejected under 35 U.S.C. 101.
The next part of the analysis involves whether the claimed invention recites additional elements that integrate the judicial exception into a practical application (Step 2A, prong two).
Given the claims are directed to a composition, the claims do not recite additional steps that integrate the judicial exception into a practical application (Step 2A, prong two: No).
The final part of the analysis involves whether the claimed invention, as a whole, recite something “significantly more” than the judicial exceptions (Step 2B).
In view of the above and considered as a whole, the claimed composition does not have markedly different characteristics from what occurs in nature and such elements discussed above are not significantly more than the indicated judicial exceptions. Thus, the claims do not qualify as eligible subject matter, and are rejected under 35 U.S.C. 101 (Step 2B: NO).
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.
RE: Claims 16-18, 20, 23, 30-31, and 36 are rejected under 35 U.S.C. 103 as being unpatentable over Ho (WO 2017/053629 A2, published March 30, 2017; cited in the Incoming Written Opinion of the International Searching Authority, filed 5/19/2023; IDS filed 12/11/2023).
Applicant amendment cancelled claims 23 and 30-31, thus making the rejection of said claims moot.
Applicant amended claim 16 to state:
A kit of parts having biological activity, the kit of parts comprising
- a first target comprising a first protein,
- a second target, coupled to comprising a liposome, exosome, DNA, RNA, viral protein, transcription factor, or small molecule,
wherein the first protein and the second protein are suitable to form a heterodimer upon irradiation with ultraviolet (UV), visible or infrared light in a first wavelength range or in the dark, which can
wherein the biological activity consists of triggering both the uptake of DNA, RNA, proteins, or small molecules into a cell, and biological effects, and
wherein at least one of the first and the second target itself has reduced biological activity as compared with the heterodimer,
wherein the first protein is a phytochrome and the second protein is a phytochrome interacting partner or vice versa,
wherein the phytochrome is selected from the group consisting of PhyA, PhyB, PhyC, PhyD, PhyE, BphP1 and DrBphP and the phytochrome interacting partner is selected from the group consisting of PIF1, PIF2, PIF3, PIF4, PIF5, PIF6, PIF7, PIF8, FHY1, FHL, PpsR2, Q- PAS1 and engineered antibodies.
The above underlined amendments are merely de minimis as they are the incorporation of now cancelled claims 23, 30 and 31 into independent claim 16. As said claims were previously rejected using the same reference, the amendments are not sufficient to overcome the previous rejection of record.
Thus, the previously filed rejections are maintained and updated below for amendment.
Claims 16-18, 20, and 36 are rejected under 35 U.S.C. 103 as being unpatentable over Ho (WO 2017/053629 A2, published March 30, 2017; cited in the Incoming Written Opinion of the International Searching Authority, filed 5/19/2023; IDS filed 12/11/2023).
In regards to claim 16, and as noted supra, amended claim 16 can be interpreted as stating:
A kit of parts having biological activity, the kit of parts comprising
- a first target (not clearly defined) comprising a first protein wherein the first protein is a phytochrome and wherein the phytochrome is selected from the group consisting of PhyA, PhyB, PhyC, PhyD, PhyE, BphP1 and DrBphP,
- a second target (not clearly defined) comprising a liposome, exosome, DNA, RNA, viral protein, transcription factor, or small molecule, coupled to a second protein wherein the second protein is a phytochrome interacting partner and the phytochrome interacting partner is selected from the group consisting of PIF1, PIF2, PIF3, PIF4, PIF5, PIF6, PIF7, PIF8, FHY1, FHL, PpsR2, Q- PAS1 and engineered antibodies,
wherein the first protein and the second protein are suitable to form a heterodimer upon irradiation with ultraviolet (UV), visible or infrared light in a first wavelength range or in the dark, which can be reversed upon irradiating the heterodimer with UV, visible or infrared light in a second wavelength range or in the dark, wherein the second wavelength range is different from the first wavelength range (functional language taken into account for examination purposes),
wherein the biological activity consists of triggering both the uptake of DNA, RNA, proteins, or small molecules into a cell (cell is not positively recited as being required by the kit), and biological effects, (i.e., said biological activity is an intended use of the kit does not provide additional structural elements to the claimed product) and
wherein at least one of the first and the second target itself has reduced biological activity as compared with the heterodimer (functional language).
Ho teaches [0007] optogenetics offers a molecular toolbox of light-switchable proteins and among the photo-switchable proteins, phytochrome-family proteins are powerful because they can be activated by one wavelength and deactivated by a second wavelength, allowing control over the degree of activation in live cells in space and time. Ho teaches, for example, Phytochrome B (PhyB) has been used for light-switchable transcription, signal cascade activation, actin nucleation, autocatalytic protein splicing, and pseudopodia elongation. Ho teaches the apo form of PhyB from A. thaliana covalently binds to the tetrapyrrole chromophore phycocyanobilin (PCB) to form the holoprotein, after which PhyB rapidly associates with and dissociates from phytochrome interacting factor 6 (PIF6) upon absorption of red (R, Amax= 650nm) photons or far-red (FR, Amax=750nm) photons, respectively. Ho teaches the PhyB/PIF6 system dimerizes in seconds, is amenable to fusion proteins, and is non-toxic to mammalian cells [0007].
FIGURE 9A of Ho shows the expected mechanism for light-activable gene delivery using VNP-PIF6 in the presence of PhyB with a NLS fusion under deactivating (Far Red, left panel) light and activating (Red, right panel) light. Under activating conditions, the PhyB-NLS adopts a conformation capable of binding PIF6 and binds the VNP-PIF6 which enhances nuclear uptake of the virus through the NLS, while under deactivating conditions and/or ambient conditions, the PIF6 dissociates from and does not bind the PhyB-NLS, resulting in basal levels of nuclear uptake (Fig 9A, [0160]).
Thus, [0053] FIGURE 9A of Ho depicts a mechanism for decreasing or increasing nuclear uptake of a virus displaying an optogenetic binding partner (PIF6) on its surface into a target cell where an optogenetic protein (PhyB) and its associated chromophore are present to form the holoprotein (Pr and Pfr) in the cytoplasm, the optogenetic protein having a nuclear localization signal (NLS) on its surface and exposing the system to far-red (inactivating) light or red (activating light) to decrease or enhance nuclear uptake of the virus, respectively ([0053, Fig 9A).
Fig 9A, Ho
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Ho additionally teaches the virus (VNP) can further include a nucleic acid molecule which can be a therapeutic nucleic acid molecule and said therapeutic molecule may be RNAi or a CRISPR/Cas genome editing tool [0121]. Examiner notes the instant specification (p7) teaches the biological effects of the claimed invention are caused by the DNA/RNAi, etc provided by the heterodimer (i.e., the therapeutic molecule comprised within the virus). Said therapeutic molecule may have biological effects on signal transduction, gene transcription, etc. Thus, the therapeutic molecule of Ho would inherently cause “biological effects” in the target cell. Further, and as noted supra, the claimed biological activity is an intended use of the claimed product.
Therefore, the invention of Ho teaches a method for delivering a nucleic acid molecule to the nucleus of a target cell, (i.e., the method of Ho teaches the uptake of a nucleic acid molecule into a cell) comprising obtaining a virus comprising a nucleic acid molecule and further comprising an optogenetic binding partner (i.e., PIF6), delivering the virus to a target cell containing an optogenetic protein (i.e., PhyB) which further comprises a nuclear localization signal and which is capable of binding the optogenetic binding partner (i.e., PIF6) present on the surface of the virus, exposing the target cell to light of a sufficient wavelength to induce conformational change in the optogenetic protein (i.e., PhyB) that allows the optogenetic protein (PhyB) to bind to the optogenetic binding partner (PIF6) on the surface of the virus, thereby enhancing nuclear delivery of the virus.
Thus, Ho teaches:
- a first target (i.e., a nuclear localization signal, NLS) comprising a first protein wherein the first protein is a phytochrome and wherein the phytochrome is PhyB,
- a second target (i.e., a viral nanoparticle, VNP) comprising DNA or RNA (i.e., a nucleic acid molecule), coupled to a second protein wherein the second protein is a phytochrome interacting partner and the phytochrome interacting partner is PIF6,
wherein the first protein and the second protein are suitable to form a heterodimer upon irradiation with ultraviolet (UV), visible or infrared light in a first wavelength range or in the dark, which can be reversed upon irradiating the heterodimer with UV, visible or infrared light in a second wavelength range or in the dark, wherein the second wavelength range is different from the first wavelength range (functional language taken into account for examination purposes),
wherein the biological activity consists of triggering both the uptake of DNA, RNA, proteins, or small molecules into a cell (cell is not positively recited as being required by the kit), and biological effects, (i.e., said biological activity is an intended use of the kit and does not provide additional structural elements to the claimed product but Ho teaches of said limitation) and
wherein at least one of the first and the second target itself has reduced biological activity as compared with the heterodimer (i.e., the first and second targets/proteins do not have as great of a nuclear uptake of the therapeutic molecule as compared with the heterodimer) (functional language but Ho teaches of said limitation).
In regards to a kit of parts, Ho teaches of a kit including the virus and nucleic acid molecule of the invention (i.e., the second target comprising a second protein) [0104]. Ho does not teach a kit comprising a first target comprising a first protein. However, it would have been prima facie obvious to one having ordinary skill in the art at the time of the invention to collect both the first target comprising a first protein and the second target comprising a second protein into a single container (e.g. kit) for the predictable result of providing the composition in convenient packaging for distribution, thus meeting the limitation of claim 16. One of ordinary skill in the art would have been motivated to modify the kit of Ho in order to provide the components in a manner that is convenient for saving time and provides easier distribution of the composition components; thus one would have had a reasonable expectation of successfully collecting these items into a single container (e.g. kit) for the predictable result of providing the composition in convenient packaging for distribution.
Therefore, the claim is obvious and is properly rejected.
In regards to claim 17, Ho teaches claim 16. Further, Ho teaches the target cell can be in a human subject [0131]. As Ho does not teach the cell is genetically modified, it is thus assumed said target cells may be genetically unmodified.
Therefore, the claim is obvious and is properly rejected.
In regards to claim 18, Ho teaches claim 16. Further, and as discussed supra in regards to claim 16, Ho teaches of a nuclear localization signal which reads on “the first target”. As a POSITA will appreciate, nuclear localization signals bind receptor proteins to initiate transport into the nucleus. Thus, Ho teaches wherein the first target is suitable to bind a protein. Therefore, the claim is obvious and is properly rejected.
In regards to claim 20, Ho teaches claim 18. Further, and as discussed supra in regards to claim 18, Ho teaches wherein the first target (i.e., the nuclear localization signal) is suitable to bind to a protein (i.e., a nuclear receptor protein). Examiner notes the specification teaches the biological effects of the present invention are caused by DNA/RNA/proteins etc provided by the heterodimer (p7). As the first target binding (i.e., the nuclear localization signal) to a protein (i.e., a nuclear receptor protein) and the subsequent biological effects of said binding (i.e., movement into the nucleus) is not caused by the heterodimer, (i.e., the biological effects of binding of the heterodimer would cause the nucleic acid molecule of the virus (i.e. second target) to be transported into the nucleus), Examiner thus notes the teachings of Ho read on the limitations of the instant claim. Therefore, the claim is obvious and is properly rejected.
In regards to claim 36, Ho teaches claim 16. Further, Ho teaches of the nucleotide sequences for the 2nd target (i.e., an AAV virus) and the second protein (i.e., PIF6) [0111], [0106]. Ho additionally teaches of the nucleotide sequences for the first protein (i.e., PhyB) [0112] and first target (i.e., nuclear localization signal) [0123].
Thus, as Ho teaches the limitations of claim 16 and thus a kit encompassing the first target comprising a first protein and a second target comprising a second protein as well as teaching said proteins form a heterodimer when exposed to light, it would thus be prima facie obvious to one having ordinary skill in the art at the time of the invention to collect the nucleotide sequences for both a first nucleotide sequence encoding a first target protein, as taught by Ho, as well as a second nucleotide sequence encoding a second target sequence, as taught by Ho, into a single container (e.g. kit) for the predictable result of providing the composition, in the initial nucleotide sequence state, in convenient packaging for distribution, thus meeting the limitation of claim 36. One of ordinary skill in the art would have been motivated to modify the kit of Ho in order to provide the components in their initial nucleotide sequences in a manner that is convenient for saving time and provides easier distribution of the composition components; thus one would have had a reasonable expectation of successfully collecting these items into a single container (e.g. kit) for the predictable result of providing the composition, in the initial nucleotide sequences, in convenient packaging for distribution.
Therefore, the claim is obvious and is properly rejected.
Response to Remarks/Amendment
RE: Rejections under 101
In response to Applicant remarks regarding the 101 rejection and specifically to Applicant remarks stating the amended claims do not encompass a naturally occurring product, Examiner respectfully directs Applicant to the above discussed 101 rejection in which Examiner explains why the amended claims do encompass a naturally occurring product.
RE: Rejections under 112b
In response to Applicant remarks stating one of skill in the art would understand the metes and bounds of the present claims, especially when read in view of the as-filed specification, Examiner respectfully directs Applicant to the above discussed 112b rejection in which Examiner explains why the claims continue to be unclear.
RE: Rejections under 103
Applicant remarks state that Ho requires the presence of a genetically modified cell that has been genetically engineered to produce the intracellular optogenetic protein. Applicant remarks further state that in the present invention, the cell does not need to be genetically engineered to contain an optogenetic protein in the cytoplasm. Instead, the optogenetic protein and the optogenetic binding partner are provided and can interact with each other on the outside of the cell. Applicant remarks note this is a major difference as it allows for the transduction of native cells, whereas the system of Ho can only be used with cells that have been previously genetically engineered to produce the intracellular optogenetic protein.
Applicant remarks have been considered but have not been found persuasive. Applicant remarks are addressing a limitation that is not positively recited by the language of claim 16 as currently written. Claim 16 does not require a cell. Thus, Applicant’s remarks stating that in the present invention, the cell does not need to be genetically engineered to contain an optogenetic protein in the cytoplasm, are not directed towards the claim language as currently written.
Applicant remarks state in Ho, the uptake of DNA, RNA, proteins, etc into the target cell itself does not occur selectively, rather Ho describes the uptake into the nucleus when the cytoplasm of the cell is modified to contain the optogenetic protein that is triggered by irradiation with light.
Applicant remarks have been considered but have not been found persuasive. Examiner respectfully notes said remarks are addressing a limitation that is not required by the language of claim 16 as currently written. The claim does not require the uptake into the target cell itself to occur selectively. The biological activity of the kit of triggering the uptake into a cell is an intended use of the kit and thus does not provide additional structural limitations to the claimed kit. The kit itself does not require a cell for said biological activity to occur. The kit does not positively recite a cell as a limitation.
Applicant remarks state a POSITA would not have predicted that both the first target and the second target could have been successfully delivered together into a single container as part of a kit in convenient packaging for distribution. Applicant remarks further state Ho teaches the target cell should be genetically modified to express the optogenetic protein.
Examiner respectfully notes the claims do not require the kit to be in a single container and further, as discussed supra, the claims do not require a cell.
If Applicant would find an interview to discuss the instant invention helpful, please do not hesitate to reach out to the examiner.
Conclusion
No claims are allowable. No claims are free of the prior art.
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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KATHERINE R SMALL whose telephone number is (703)756-4783. The examiner can normally be reached Monday - Friday 8:30am-4pm.
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/KATHERINE R SMALL/Examiner, Art Unit 1633
/EVELYN Y PYLA/Primary Examiner, Art Unit 1633
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