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 .
Claim Status
The preliminary amendment filed 04/20/23 is acknowledged. No restriction is being imposed in this case. Claims 1-13 are pending and under review.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code [see p. 10, par. 2]. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claims 1, 6, and 13 are objected to because of the following informalities: Regarding claim 13, the use of a comma to separate two elements is improper. When only two elements are intended, they should be joined by a conjunction such as “and” or “or” without a comma.
The phrase “as setting forth” in claim 1 is improper because it suggests an active step of “setting forth.” An example of a grammatically correct phrase would be “as set forth.” The phrase “initiating a cellular signaling” in claim 6 is grammatically improper because cellular signaling is a process and not a countable noun. Amendment to “Initiating a cellular signal” or “initiating cellular signaling” is suggested. Appropriate correction is required.
Claim Rejections - 35 USC § 112b
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 2-9 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 6 recites the limitation "administering a plurality of modified proteins wherein the modified protein is a modified interferon gamma". There is insufficient antecedent basis for this limitation in the claim. The term “the modified protein” refers back to a “plurality of modified proteins,” creating ambiguity as to whether the limitation applies to each protein of the plurality, an individual modified protein within the plurality, or some other subset thereof. To advance compact prosecution, this limitation is interpreted as “administering a plurality of a modified protein wherein the modified protein is a modified interferon gamma,” such that a plurality of a single species of protein is administered. Claims 7-9 are also rejected for depending upon an indefinite claim without correcting the indefiniteness.
Claims 2, 5, and 9 recite “the formed IFN- γ” and refers back to independent claim 1. However, claim 1 only recites “a modified protein of IFN- γ” and does not introduce “a formed IFN- γ.” To advance compact prosecution, this phrase is interpreted as “the modified IFN- γ.” Claims 3 and 4 are also rejected for depending from an indefinite claim without correcting the indefiniteness. Appropriate correction is required.
Therefore, claims 2-9 are rejected under 35 U.S.C. 112(b) for lack of antecedent basis.
Claim Rejections - 35 USC § 112a
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, 2, 6, 9, 10 and 13 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 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 MPEP 2163(II)(3)(a)(i)(A), reduction to drawings MPEP 2163(II)(3)(a)(i)(B), 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 MPEP 2163(II)(3)(a)(i)(C).
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant has possession of and what Applicant is claiming. Independent claims 1, 6, and 10 recite “at least one modification of an amino acid at a position from 27-40 of SEQ ID NO: 1, wherein the IFN is capable of inducing an immune response,” which encompasses a genus of proteins. The specification, however, only demonstrates that substitutions to positions 27, 29, and 30 or deletion of positions 27-33 still produce a functional IFN protein and it is clear that Applicant is in possession of these species. The claims, however, are not limited to those species but instead encompass modifications at any position within residues 27-40 of SEQ ID NO: 1 without presenting a representative number of species within the recited genus, adequate structure-function correlation, or other identifying characteristics of the genus as a whole.
The amino acid sequence consisting of positions 27-40 are within and around helix B of the IFN- γ [see Yasamut et al., IDS ref NO: 26, p. 5, par. 1, lines 7 and 8]. Modifications both in and around alpha helices can drastically influence protein function. The art teaches that a single point mutation in the F helix of IFN- γ at position H111 renders the protein inactive [see Zuber et al., p. 550, col. 2, par. 1, lines 1-6], that modifications near loops can affect protein function [see Lundell et al., p. 16160, col. 1, par. 2, lines 15-22], and that modifications of amino acids can alter receptor binding independent of conformational changes [see Lundell et al, abstract, lines 9-13]. These findings underscore that the effects of amino acid substitutions in IFN- γ are highly unpredictable and not interchangeable. Accordingly, the disclosure does not reasonably convey possession of the full scope of modifications across all positions. Claims 2, 9, and 13 are rejected for explicitly or implicitly requiring the composition of claim 1.
Therefore, claims 1, 2, 6, 9, 10, and 13 are rejected for lack of written description.
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, 2, 10, and 13 are rejected under 35 U.S.C. 101 because do not constitute patent eligible subject matter.
Claims 1 and 2 are drawn to a modified IFN- γ and claims 10 and 13 are drawn to a vector comprising a modified IFN- γ.
Claims 1 and 2 are drawn to compositions, which are a statutory class (Step 1: Yes). The claims recite a modified IFN- γ protein whose structure encompasses the naturally occurring IFN- γ structure found in several species, including the Indochinese rhesus macaque [see Uniprot accession number P63310, p. 5; sequence alignment below], and therefore recites a judicial exception (Step 2A, Prong 1: Yes). According to Step 2A, Prong 2, set forth in 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) through (c), (e), and (h). Claims 1 and 2 are drawn to the composition itself and do not recite additional elements that reflect an improvement within the technical field, recite additional elements that apply the natural phenomena judicial exception to a particular treatment or which utilize a particular machine, provide additional elements that effect a transformation, or provide additional elements that apply the judicial exception in some other meaningful way (STEP 2A, Prong Two: No). The claims are therefore directed only to the naturally occurring protein rather than to a practical application of that protein, and the discovery of a naturally-occurring product does not amount to significantly more: "Groundbreaking, innovative, or even brilliant discovery does not by itself satisfy the § 101 inquiry." Myriad, 133 S. Ct. at 2117. (Step 2B: No).
Therefore, claims 1 and 2are rejected under 35 U.S.C. 101 as they do not constitute patent eligible subject matter.
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Instant SEQ ID NO: 1 aligned to Indochinese rhesus macaque
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.
Claims 1-5 and 10-12 are rejected under 35 U.S.C. 102a1 as being anticipated by Van Den Hazel et al. (US20060099175A1).
Claims 1 and 2 are drawn to a modified IFN- γ, claims 3-5 are drawn to specific modifications and protein properties, and claims 10-12 are drawn to a vector comprising a modified IFN- γ.
Van Den Hazel et al. discloses an IFN- γ polypeptide exhibiting receptor binding activity that induces the transduction of a signal [see specification, p. 6, col. 1, par. 71, lines 1-7] (which is understood to be inducing a signal towards an immune response given that IFN-γ signaling is one mechanism that induces an immune response), and consisting of up to 10 residue modifications [see claim 1] (instant claim 1). The disclosed IFN- γ is enumerated in SEQ ID NO: 1 and corresponds to instant SEQ ID NO: 1 [see claim 1 and alignment below] (instant claim 1). Van Den Hazel et al. discloses that the polypeptide has an N-glycosylation site introduced by the substitution E38N [see claims 1 and 28 (instant claim 1) and that the naturally occurring N-glycosylation site located at position 25 may be removed, preferably by substitutions of N25G and T27P [see specification, p. 16, col. 1, par. 309] (instant claims 1, 3, and 4). Regarding instant claim 2, a discontinuous epitope is a binding site formed by amino acid residues that are separated in the protein’s primary sequence but brought together in space through protein folding. Given that positions 27-40 comprise the claimed discontinuous epitope, any modification to the claimed positions 27-40 would necessarily alter a discontinuous epitope of the IFN- γ as said modification would necessarily produce a difference compared to the reference sequence. Therefore, the art inherently reads on this claim (instant claim 2). Furthermore, given that the modified amino acid comprises the claimed structural modifications, it would be inherent that the modified protein would be resistant to an autoantibody capable of neutralizing IFN- γ at the discontinuous epitope comprising positions 27-40 even if not disclosed by the prior art (instant claim 5). Van Den Hazel et al. discloses that the polypeptide may be encoded in a vector and that the vector may be a plasmid or viral vector [see specification, p. 21, col. 2, par. 361, lines 1-5] (instant claims 10-12).
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Van Den Hazel et al. SEQ ID NO: 1 aligned to instant SEQ ID NO: 1
Therefore, claims 1-5 and 10-12 are rejected under 35 U.S.C. 102a1.
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.
Claims 1-12 are rejected under 35 U.S.C. 103 as being unpatentable over Van Den Hazel et al. (US20060099175A1) in view of Harada et al., and in further view of Chawansuntati et al.
Claims 1 and 2 are drawn to a modified IFN- γ, claims 3-5 are drawn to specific modifications and protein properties, and claims 6-9 a drawn to methods of use of the modified IFN- γ.
Adult-onset immunodeficiency (AOID) is defined in the art as a condition characterized by the presence of anti- IFN- γ antibodies in adults with multiple opportunistic infections similar to those observed in patients with advanced human immunodeficiency virus (HIV) infection [see Chawansuntati et al., p. 790, col. 1, par. 1, lines 1-6]. Chawansuntati et al. notes that disseminated nontuberculous mycobacterial (NTM) infection is the most common infectious disease in patients with AOID [see p. 791, col. 2, par. 3, lines 1-8]. Harada et al. discloses a case report regarding a patient with autoantibodies against IFN- γ , negative for HIV, and diagnosed with disseminated nontuberculous mycobacterial infection (NTM). One of ordinary skill in the art would have identified this patient as suffering from AOID or at least as exhibiting the characteristic clinical features of AOID, given that the patient’s symptoms meet the ordinary meaning of AOID in the art. Harada et al. discloses that subcutaneous administration of recombinant IFN- γ was useful for the treatment of disseminated nontuberculous mycobacterial infection in this patient with IFN- γ autoantibodies [see p. 376, col. 1, par. 1, lines 8-11].
The combination of Chawansuntati et al. and Harada et al. do not teach or suggest the modified protein of the instant application.
Van Den Hazel et al. discloses an IFN-γ (identified in Van Den Hazel et al. by the alternative name of IFNG) polypeptide exhibiting normal IFN-γ functions, such as receptor binding activity that induces transduction of a signal [see specification, p. 6, col. 1, par. 71, lines 1-7] (which is understood to be inducing a signal towards an immune response given that IFN-γ signaling is one mechanism that induces an immune response)and consisting of up to 10 residue modifications [see claim 1] (instant claim 1). The disclosed IFN-γ is enumerated in SEQ ID NO: 1 and corresponds to instant SEQ ID NO: 1 [see claim 1 and alignment above] (instant claim 1). Van Den Hazel et al. discloses that the polypeptide has an N-glycosylation site introduced by the substitution E38N [see claim 27] (instant claim 1) and that the naturally occurring N-glycosylation site located at position 25 may be removed, preferably by substitutions of N25G and T27P [see specification, p. 16, col. 1, par. 309] (instant claims 1, 3, and 4). Regarding instant claim 2, given that positions 27-40 comprise the claimed discontinuous epitope, any modification to the claimed region of positions 27-40 would necessarily alter a discontinuous epitope of the IFN-γ as said modification would necessarily produce a difference compared to the reference sequence, and therefore the art inherently reads on this claim (instant claim 2). Furthermore, given that the modified amino acid comprises the claimed structural modifications, it would be inherent that the modified protein would be resistant to an autoantibody capable of neutralizing IFN- γ at the discontinuous epitope comprising positions 27-40 even if not disclosed by the prior art (instant claim 5). Van Den Hazel et al. discloses that the polypeptide may be encoded in a vector and that the vector may be a plasmid or viral vector [see specification, p. 21, col. 2, par. 361, lines 1-5] (instant claims 10-12). Van Den Hazel et al. discloses that the benefit of this peptide is that it inhibits C-terminal truncation of the IFN- γ polypeptide by proteases [see specification, p. 1, col. 2, par. 14] and that the disclosed polypeptide can be administered for the treatment of autoimmune diseases [see specification, p. 24, col. 1, par. 387, line 8].
It would have been obvious to combine these teachings and administer the polypeptide of Van Den Hazel et al. to initiate an immune response in a subject with AOID given that Harada et al. identifies AOID as an autoimmune disease through which administration of IFN-γ can provides therapeutic benefits, and Van Den Hazel et al. discloses a modified IFN-γ that is resistant to autoantibodies against IFN-γ and is disclosed to be useful for the treatment of autoimmune diseases. Furthermore, there would be an expectation of success as Harada et al. discloses that IFN-γ has therapeutic benefits and the modified protein of Van Den Hazel et al. has normal IFN-γ functions, with the additional benefit of the protein being resistant to degradation by proteases and autoantibodies as discussed above (instant claims 6-9).
Therefore, claims 1-12 are rejected under 35 U.S.C. 103.
Claims 1-5 and 10-13 are rejected under 35 U.S.C. 103 as being unpatentable over Van Den Hazel et al. (US20060099175A1) in view of Arbabi et al.
Claims 1 and 2 are drawn to a modified IFN- γ, claims 3-5 are drawn to specific modifications and protein properties, and claims 10-13 are drawn to a vector comprising a modified IFN- γ.
Van Den Hazel et al. discloses an IFN- γ polypeptide exhibiting receptor binding activity and consisting of up to 10 residue modifications [see claim 1] (instant claim 1). The disclosed IFN- γ is enumerated in SEQ ID NO: 1 and corresponds to instant SEQ ID NO: 1 [see claim 1 and alignment above] (instant claim 1). Van Den Hazel et al. discloses that the polypeptide has an N-glycosylation site introduced by the substitution E38N [see claim 27] (instant claim 1) and that the naturally occurring N-glycosylation site located at position 25 may be removed, preferably by substitutions of N25G and T27P [see specification, p. 16, col. 1, par. 309] (instant claims 1, 3, and 4). Regarding instant claim 2, any modification to the claimed region of positions 27-40 would necessarily alter a discontinuous epitope of the IFN- γ as said modification would necessarily produce a difference compared to the reference sequence, and therefore the art inherently reads on this claim (instant claim 2). Furthermore, given that the modified amino acid comprises the claimed structural modifications, it would be inherent that the modified protein would be resistant to an autoantibody capable of neutralizing IFN- γ at the discontinuous epitope comprising positions 27-40 even if not disclosed by the prior art (instant claim 5). Van Den Hazel et al. discloses that the polypeptide may be encoded in a vector and that the vector may be a plasmid or viral vector [see specification, p. 21, col. 2, par. 361, lines 1-5] (instant claims 10-12).
Van Den Hazel et al. does not disclose or suggest that the vector is a pET21a vector.
Arbabi et al. discloses cloning IFN- γ into a pET21a vector [see p. 91, par. 3, lines 1-3], described as a suitable expression vector [see p. 88, col. 1, par. 2, lines 1-3], and expressing proteins utilizing this vector [see p. 91, par. 3, lines 8-10].
It would have been obvious to combine these teachings and encode the disclosed polypeptide of Van Den Hazel et al. into a pET21a vector as Arbabi et al. discloses that this vector is suitable for the expression of IFN- γ. Furthermore, utilizing this known vector would provide a predictable expectation of success.
Therefore, claims 1-5 and 10-13 are rejected under 35 U.S.C. 103.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Tirone D Johnson whose telephone number is (571)272-1256. The examiner can normally be reached M-F, 9-5 ET.
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/TIRONE D. JOHNSON/Examiner, Art Unit 1675
/Adam Weidner/Primary Examiner, Art Unit 1675
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