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 .
Restriction/Election
Applicant’s election without traverse of group I, claims 1, 3, 5-7, 12, 13, 16, 17, 19, 22, 27, 28 and 45 in the reply filed on 04/10/26 is acknowledged.
Claims 20, 21, 29, 30, 32-39, 43, 44 and 46-65 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 04/10/26.
Objections
Claims 17 and 19-22 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
These claims are free of the prior art discussed below because there is no reasonable expectation of success for the specific fusion protein combinations claimed, which invalidates a rejection of obviousness. As will be discussed below, the J proteins “comprise” a J domain, but the remaining portions of the protein are not structurally conserved, and the fusion combination is unpredictable where the linker/Dnaj/Q are solely claimed by functional terms that are only supported for the J domain and examples showing its binding ability when combined with a particular polyglutamine binding domain that is also structurally described. This structural component distinguishes the allowable subject matter in terms of the 112(A) rejection.
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 1, 3, 5, 6, 12, 13, 16, 27, 28 and 45 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 claims are drawn to any J protein fused to any polyglutamine binding domain.
MPEP § 2137 states that "the written description requirement for a genus must be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, 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.
For written description, the analysis (a) considers actual reduction to practice, (b) disclosure of drawing or structural chemical formulas, (c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties, functional characteristics when coupled with known or disclosed and (d) representative number of examples.
actual reduction to practice/(b) disclosure of drawing or structural chemical formulas:
The specification discloses 170 sequences, of which 89-157 are functional fusion proteins, as claimed, for their polyglutamine binding ability and protein aggregation disorder treatments. It is clear from the art and the specification that the J domain is highly conserved, and the examples of fusion proteins “consisting” of the J domain are supported by the specification. However, there are no examples of full length hsp40/J proteins bound to polyglutamine that function to bind it as claimed, and treat protein aggregation disorders, as discussed in the specification.
(c ) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties
The art recognizes that hsp40 proteins are functionally hsp70 chaperones, which are analogous to J Proteins (those requiring this domain), but the art also recognizes that the remaining portions outside of the J domain of J proteins do not have predictable functionality. These structural differences of fusion proteins “comprising” a J domain can cause significant changes in the ability of full length hsp40/J proteins to bind hsp70, as well as to bind other target proteins that they chaperone for disease treatments (Summers et al. Trends Biochem Sci. 2009 May;34(5):230-3).
(d) Representative number of examples
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. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]." See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004)("[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.").
There are no example of fusion proteins “comprising” full length hsp40/J proteins. Given this lack of description in the specification, the application fails to describe the claimed invention in such a full, clear, and concise and exact terms that a skilled artisan would recognize that applicants were in possession of the genus of claimed invention.
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.
Claim(s) 1, 3, 12, 13, 16, 27, 28 and 45 are rejected under 35 U.S.C. 103 as being unpatentable over Nukina et al. (US2010/0016221) in view of Fan et al. (Cell Stress Chaperones. 2003, Oct; 8(4):309–316).
Nukina teaches a method of degrading a target protein in a subject comprising administrating to the subject an effective amount of any of a peptide comprising an HSC70-binding moiety, and a target protein-binding moiety (abstract). This reference teaches that such peptides comprise and treat polyglutamine diseases, such as Huntington's disease [0016]. This reference further teaches that the target protein-binding moiety comprises a Polyglutamine-binding peptide 1 (QBP1), and that QBP1 is SEQ ID NO: 7, which is 100% identical to instantly claimed SEQ ID NO: 7 [0017, SEQ ID NO: 7].
The difference between the prior art and the instant claims is that the prior art does not teach hsp40 (J proteins/Dnaj) as an hsp70 binding peptide in the fusion protein.
Fan teaches that Hsp40s represent a large protein family that functions to specify the cellular action of Hsp70 chaperone proteins (abstract). This reference further teaches that Type I Hsp40s are descendants of Escherichia coli DnaJ, and 12 of the 44 Human Hsp40 have a domain structure similar to that of DnaJ (abstract). Fan also teaches that Hsp40 proteins regulate complex formation between Hsp70 and polypeptides by 3 mechanisms:
1) Hsp40 proteins have evolved to contain unique classes of polypeptide-binding domains (PPDs) that bind and deliver specific clients to Hsp70
2) Hsp40 proteins stabilize Hsp70 polypeptide complexes by driving the conversion of Hsp70 from its ATP form to the adenosine diphosphate form; and
3) specialized members of the Hsp40 family are localized to different sites within the same cellular compartment (p. 309, Col. 2).
Fan teaches that between these three binding mechanisms, Hsp70 interaction with differentially localized Hsp40s enables different Hsp70/Hsp40 pairs to bind proteins at these sites (p. 309, Col. 2).
It would have been obvious to one of ordinary skill in the art at the filing date of the invention to have taken the fusion protein of Nukina and used the hsp40 of Fan because Fan teaches that it binds hsp70 and Nukina teaches that the fusion protein requires an hsp70 binding motif to function. One would be motivated to do so because Nukina teaches a fusion protein mechanism for treating polyglutamine protein aggregation diseases and Fan teaches that hsp40 binds hsp70, which Nukina teaches as the other portion of the QBP1 fusion protein. As such, there is a reasonable expectation of success that the fusion protein of Nukina will be effective in binding hsp70 when the hsp40 of Fan is used as the hsp70 binding peptide.
This meets the limitations of claim 1 by teaching a QBP1 fusion protein with motivation to use the hsp40 of Fanas the hsp70 binding portion of Nukina for treating polyglutamine protein aggregation, when the proper binding pair is used. Claims 1, 2, 5, 6, 12, 13, 16, 27, 28 and 45 do not account for any structural requirements, leaving the protein that is capable of the claimed function to be generic to the art recognized activity of each respective class of proteins, rendering the functionally described combinations obvious.
Claim 3 is met because hsp40 is human, as discussed in Fan (abstract). Claim 12 is met because QBP1 is SEQ ID NO: 7 of Nukina, and SEQ ID NO: 57 of the instant claims. Claim 13 is met because SEQ ID NO: 57 is SEQ ID NO: 7 of Nukina. Claim 16 is rendered obvious because the linker is optional, and the most basic structural configurations are common N- to C- terminus linkages taught by Nukina [0029]. Claim 27 is met because Nukina teaches treating polyglutamine binding disease, by reducing aggregation [0003-0005]. Claim 28 is met because Nukina teaches cellular protein aggregation [0004]. Claim 29 is met because Nukina also teaches QBP1 for cytotoxicity [Example 1; 109-0110]. Claim 45 is met because Nukina teaches a pharmaceutical formulation [0060-0061].
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEANETTE M LIEB whose telephone number is (571)270-3490. The examiner can normally be reached M-F 10-7.
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/JEANETTE M LIEB/Primary Examiner, Art Unit 1654
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