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 .
Claim Status
Claims 1, 3, 11, 17, and 25-38 are currently pending in this application.
Election/Restrictions
Applicant’s election is acknowledged of the P2Y receptor species of membrane protein and ATP species of P2 receptor ligand 11 in the reply filed on Feb. 24, 2025. Claims 1, 3, 11, 17, and 25-38 have been considered on the merits.
Previous Rejections
Status of the rejections:
(a) The previous claim rejections under 112(a) are withdrawn in view of applicant’s amendments.
(b) The previous claim rejections under 102 are withdrawn in view of applicant’s amendments.
Claim Interpretation
It is noted that the claims imply that the P2Y11 or portion thereof must have the recited ATP-binding function in the context of being a fused component of the first fusion protein. Similarly, the “Arrestin or a portion thereof that binds to the membrane protein bound to ATP” of the second fusion protein is interpreted to be required to have its binding function in the context of being a component of the second fusion protein and wherein “binding to the membrane protein” encompasses merely binding to the first fusion protein when bound to extracellular ATP. Furthermore, the Arrestin or a portion thereof in the context of the second fusion protein is interpreted to specifically or preferentially bind the membrane protein (or first fusion protein) bound to ATP over the membrane protein (or first fusion protein) lacking a bound ligand ([0038]) if the second fusion protein exhibits some level of membrane protein binding in the absence of extracellular ATP.
Claim Rejections - 35 USC § 112(a), Written Description (new)
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, 3, 11, 17, 25, 27-32, and 34-38 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.
The claimed invention as a whole is not adequately described if the claims require essential or critical elements that are not adequately described in the specification and that is not conventional in the art as of applicants effective filing date. Possession may be shown by actual reduction to practice, clear depiction of the invention in a detailed drawing, or by describing the invention with sufficient relevant identifying characteristics such that a person skilled in the art would recognize that the inventor had possession of the claimed invention. Pfaff v. Wells Electronics, Inc., 48 USPQ2d 1641,1646 (1998).
In making a determination of whether the application complies with the written description requirement under 35 U.S.C. 112(a) or 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant is claiming and what Applicant has possession of.
In the instant case, claims 1 and 11 are directed to an animal cell (or entire animal comprising the aforementioned) expressing two different fusion proteins and capable of detecting extracellular ATP wherein the (1) first fusion protein comprises (a) a membrane protein capable of binding ATP via a P2Y11 domain(s) and (b) a first reporter protein; and the (2) second fusion protein specifically or preferentially binds via (a) an Arrestin domain(s) to the membrane protein when the first fusion protein is bound to extracellular ATP and comprises (b) a second reporter protein; whereby the first and second reporter proteins can form a split reporter protein to signal detecting.
In view of dependent claims 26 and 33, claims 1 and 11 broadly encompasses the system whereby the first fusion protein comprises a portion of P2Y11 lacking a transmembrane domain. However each of claims 1 and 11 require the P2Y11 component be capable of binding to ATP, and imply this is more specifically extracellular ATP.
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 with sufficient nexus to the entire scope of the genus.
The art teaches that P2Y receptors have a helical seven transmembrane (TM) bundle structure forming a nucleotide binding pocket with ligand interactions made by residues in multiple TM domains (e.g., TM6 and TM7) as well as in the extracellular N-terminus domain and second extracellular loop (ECL2) domain (Jacobson et al., Br J Pharmacol 177: 2413-33 (2020) at Fig. 4, pg. 2421, left col., last para., to pg. 2422, left col., 3rd para.). Thus, the art teaches the P2Y11 or a portion thereof that binds to extracellular ATP must comprise transmembrane domains.
Furthermore the instant application only describes in detail a single first fusion protein (P2Y11-split Luc (C-terminal)) (SEQ ID NO: 1) using a P2Y11 receptor fragment (SEQ ID NO: 9) derived from NP_002557.2 (Examples, FIG. 3-9), which has the N-terminus of human P2Y11 and the full TM1 and TM2 domains as naturally connected by intracellular loop 1 (ICL1) based on NP_002557.2.
Nowhere does the instant application describe any fusion protein comprising only a portion of P2Y11 that binds to ATP wherein that portion lacks any transmembrane domains. Thus, the instant specification lacks a written description for sufficient number of representative species for the genus of first fusion proteins comprising a portion of P2Y11 that binds to ATP as the skilled artisan cannot envision the ATP binding portion of P2Y11 lacking any transmembrane domain.
The written description requirement may be satisfied through actual reduction to practice 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 structure and function, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed invention. The instant application fails to provide sufficient descriptive information across the breadth of the claims.
35 USC § 112(a) – Scope of Enablement (new)
Claims 1, 3, 11, 17, and 25-38 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because while the claims are enabled for wherein the first reporter protein is extracellularly or intracellularly positioned same with the second reporter protein such that upon the first and second fusion proteins forming a complex due to the Arrestin or portion thereof their close proximity results in activation of the full split reporter protein; the specification does not enable any person skilled in the art to which it pertains or with which it is most nearly connected to detect extracellular ATP wherein the first reporter protein is extracellularly positioned and the second reporter protein is intracellularly positioned or vice versa.
Claims 1 and 11 are directed to an animal cell (or entire animal comprising the aforementioned) expressing two different fusion proteins and capable of detecting extracellular ATP wherein (1) the first fusion protein comprises (a) a membrane protein capable of binding ATP via a P2Y11 domain and (b) a first reporter protein; and (2) the second fusion protein specifically or preferentially binds via (a) an Arrestin domain to the membrane protein when the first fusion protein is bound to extracellular ATP and comprises (b) a second reporter protein; whereby the first and second reporter proteins form a split reporter protein emitting a detectable signal when brought in close proximity due to the Arrestin domain specifically or preferentially binding to the membrane protein when bound to extracellular ATP as oppose to in the absence of extracellular ATP.
In must be emphasized that the claims broadly encompasses the system whereby the first reporter protein component of the first fusion protein component is at any position or location with regard to a membrane and wherein the second reporter protein may also be at any position or location with to the same membrane.
All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
The prior art teaches split luciferase systems (e.g., split NanoLuc luciferase) for detecting a purine (e.g., 2-Cl-IB-MECA) with a P1 receptor (e.g., A3 AR) fusion membrane protein binding to a β-Arrestin-2 fusion protein (Storme et al., Biochem Pharmacol 148: 289-307 (2018) at Abstract). But as the prior art does not teach any split reporter system that works across a cell outer membrane, there must be sufficient guidance to enable one of ordinary skill in the art to make/use the claimed invention with these features.
The instant specification describes working embodiments of detecting extracellular ATP using mice cells genetically modified to express both a P2Y11 fusion protein and a β-arrestin fusion protein utilizing a split luciferase reporter protein (Examples, FIG. 3-9) and specifically wherein the first fusion protein (P2Y11-split Luc (C-terminal)) (encoded by SEQ ID NO: 1). However the instant application is silent as to any details regarding a split reporter system functioning with the respective subunits on opposite sides of a membrane, such as an outer cell membrane.
Therefore extensive experimentation would be required to bridge these gaps in guidance to determine how to detect ATP wherein the first reporter protein is extracellularly positioned and the second reporter protein is intracellularly positioned or vice versa. Thus, undue and unreasonable experimentation is required to determine how to use the claimed invention wherein both reporter proteins are not on the same side of the membrane, including wherein the split reporter is a split luciferase as in dependent claims 3 and 17.
In summary, all claims are rejected under 35 U.S.C. 112(a) because the specification does not reasonably provide enablement, to a person skilled in the art to which it pertains or with which it is most nearly connected to, to make/use the claimed invention to detect extracellular ATP over the entire scope of the first and/or second fusion proteins. Given the lack of working examples, the limited guidance provided in the specification, the lack of guidance in the prior art, and the broad scope of the claims; undue and unreasonable experimentation would have been required for one skilled in the art to make/use the claimed system across the breadth recited in the claims to provide the detecting and which may never be achievable across the entire scope of the claims.
Claim Rejections - 35 USC § 112(d) (new)
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 28 and 35 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.
In claims 28 and 35, the wording in the phrase “the second fusion protein comprises a portion of an Arrestin comprising a domain that binds to the membrane protein bound to ATP” means that the second fusion protein encompasses second fusion proteins comprising a full-length Arrestin, which by definition comprises an Arrestin domain that binds to the membrane protein bound to ATP, as well as second fusion proteins wherein its Arrestin component consists of any portion of an Arrestin that binds to extracellular ATP. Thus, each of claims 28 and 35 encompasses the full genus of second fusion proteins comprising an Arrestin or a portion thereof that binds to the membrane protein bound to ATP as in claims 1 and 11, respectively. 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.
Conclusion
No claim is allowed.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERIC J ROGERS whose telephone number is (571)272-8338. The examiner can normally be reached Monday - Friday 9:00-6:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Tracy Vivlemore, can be reached on 571-272-2914. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ERIC J ROGERS/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638