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 .
Priority
This application is a National-Stage entry (371) of PCT/US2021/054869, filed 10/13/2021. Applicant claims domestic benefit under 35 U.S.C. 199(e) to U.S. Provisional Patent Application No. 63/091,267, filed on 10/13/2020.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 10/18/2023 and 1/6/2026 are acknowledged. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Election/Restrictions
Applicant’s election of Group I (claims 1-4 and 9), in the reply filed on 1/6/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
The requirement is still deemed proper and is therefore made FINAL.
Claims 5-8 and 10-13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 1-4 and 9 are pending and have been examined on the merits.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency 1 – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
Sequences of more than 4 specified amino acids must be identified by SEQ ID NO. Such sequences without proper identification include those recited in Table 1, on pages 43-44, and the sequences in lines 3-5 of page 74.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specific deficiency 2 – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings. Specifically, these include the sequences depicted in of FIGs 12; 13; 50A-C, and 53A-C.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
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, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specification
The disclosure is objected to because of the following informalities:
TRADE NAMES, TRADEMARKS, AND OTHER MARKS USED IN COMMERCE:
The use of the terms SPECTRAMAX (pg. 53); One Shot™ (pg. 53); Origami™ B (pg. 53); Superdex™ (pg. 54); Kimwipe™ (pg. 55, pg. 73); Frontier™ (pg. 71); and Sigmacote® (pg. 72); which are each a trade name or a mark used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms. This is not an exhaustive list and Applicant’s attention to identifying any other trademarks/trade names is requested.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks (see MPEP 608.01(v) and 608.01(u)).
Appropriate correction is required.
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.
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 1-4 and 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 1 and dependent claims refer to positive and negative peptides. The definition of negative peptide is not clear. The positive peptide is defined by the SEQ ID NOs structures recited. However, the negative peptide is not defined. Clarification is requested about what makes a negative peptide. Is it 3 consecutive amino acids with negatively charged amino acid and/or hydrophobic amino acid residues, where at least one is negatively charged and one is a hydrophobic amino acid in the whole peptide polymer chain?
Claim 3 recites: the charge complementary self-assembling peptides of claim 1 or claim 2,wherein a uricase enzyme is attached to a positive and/or negative peptide at a position between the N and/or C termini of the positive and/or negative peptide.
Claim 9 recites: the charge complementary self-assembling peptides of claim 2, wherein a uricase enzyme is attached to a positive and/or negative peptide at a position between the N and/or C termini of the positive and/or negative peptide.
Claims 3 and 9 each recite “a uricase enzyme is attached to a positive and/or negative peptide at a position between the N and/or C termini of the positive and/or negative peptide”. This limitation is indefinite as it is impossible to determine the meaning of the claimed subject matter. An peptide sequence is traditionally a linear sequence of amino acids linked by carboxylic bonds, beginning with a N-terminus and ending in a C-terminus. It is unclear how the uricase enzyme could be attached at a position between the N- and/or C- termini of a peptide. The use of “and/or” renders this limitation impossible to determine. The enzyme sequence may be internal to the other peptide sequences, and thus could be found “between the N and C termini” but in no way could it be “or” as a peptide has to have both of these termini present. Further, theoretically, the uricase enzyme could be attached through a chemical crosslinker to a reactive side chain residue, typically a cysteine or lysine. However, such an arrangement is not explicitly described and would still be attached “between” the two termini of the other peptide.
The resulting claims are considered indefinite because the claims do not clearly set forth the metes and bounds of the patent protection desired.
Claims 3 and 9 are rejected under 35 U.S.C. § 112(b) for indefiniteness.
All other claims depend directly or indirectly from the rejected claim 1 and are, therefore, also rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, for the reasons set forth above.
For the purposes of compact prosecution, this claim element has been interpreted under the broadest reasonable interpretation (B.R.I.) in light of the specification to be referring to a peptide in which the amino acid sequence of the uricase enzyme is internal to the sequence of the negative or positive peptides to which it is attached, i.e. at a position between the N-terminus and C-terminus.
Claim Rejections - 35 USC § 112(a)- Written Description
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 1-4 and 9 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 claims 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.
MPEP 2163.03(V) states that an original claim may lack written description support when a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349-50 (Fed. Cir. 2010) (en banc).
In the instant case, claims 1-4 and 9 are each so broad as to encompass fusion proteins having any uricase enzyme. Thus, the claims are drawn to fusion proteins with the entire genus of all uricase enzymes.
Comparatively, the specification only recites a small number of species of the broad genus that meets the recited limitations.
MPEP § 2163.(II)(A)(3)(a) states that 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 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 inventor was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
The specification fails to reasonably describe the full genus of the claimed invention by providing identifying characteristics or functional properties of the bacteria and compositions thereof so that one can predict or conclude that the Applicants were in possession of more species than those reduced to practice herein.
The instant specification does not disclose relevant identifying characteristics, such as key physical properties or functional characteristics of the enzymes and the sequences that comprise the enzymes such that the entirety of the claimed genus is encompassed by the description in the disclosure.
The specification generally teaches that the uricase may be a wild-type uricase, and may be an animal uricase, a mammalian uricase, or a human uricase (pg. 7, lines 11-14).
The specification also states that “In some embodiments, a uricase cargo polypeptide comprises an amino acid sequence with at least 70% identity to SEQ ID NO: 9 (FIG. 59 ). In some embodiments, a uricase cargo polypeptide comprises a sequence of SEQ ID NO: 9. In some embodiments, a uricase cargo polypeptide comprises an amino acid sequence encoded by a nucleic acid sequence comprising a sequence with at least 70% identity to the sequence of SEQ ID NO: 10 (FIG. 59)” (see page 7, lines 15-31; and also page 37-38).
The disclosure does not provide any teachings or guidance about the structure or identifying characteristics of uricase, such that the disclosure amounts to a correlation between structure and function in the entire genus of enzymes. Further, practically speaking, the disclosure only contains a singular uricase structure, contained in SEQ ID NO:9, as described above. There is no evidence that entire breadth of the genus has been considered.
The disclosure provides examples of a single uricase-CATCH fusion protein that was reduced to practice, as described in FIG. 55B and FIG. 59 (see Examples 4 and 5 on pages 75-76 of the specification). The description in the specification does not explicitly state what uricase sequences was used, but one can ascertain from FIG. 59 that the fusion proteins reduced to practice included the amino acid sequences of SEQ ID NO: 9 encoded by the nucleic acid sequence of SEQ ID NO: 10. The specification demonstrates that a uricase-loaded gel having this CATCH-uricase fusion protein is able to deplete uric acid crystals in vitro (pages 75-76, FIGs. 57-61) and potentially provide therapeutic benefit in an animal gout model (pages 76-77, FIG. 62). However, this can only be said for this singular embodiment of the fusion protein.
When turning to the relevant state of the art, Boca et al. (US PGPub No. 20180258406) teaches uricase sequences having beneficial effects and methods of treating patients suffering from hyperuricemia (Abstract). Boca teaches that a functional uricase can be found in a wide range of organisms, such as archaea, bacteria, and eukaryotes, but that in humans and some primates uricase is not expressed ([0004]). Boca teaches two known recombinant uricases used as therapeutics ([0008]), one of which is a chimera and the other is a modified recombinant Aspergillus flavus uricase ([0008]-[0009]).
Boca also discloses that a uricase according to the invention therein may comprise an amino acid sequence that is at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOS: 1-34 disclosed therein ([0012] and Table 1).
Elsewhere Boca describes analyzing the sequences of more than 200 uricase sequences from publicly-available databases were studied, from which 8 candidate sequences were chosen for further investigation and optimization ([0074]-[0076]), and only some of these had further success, and ultimately only two, from Deinococcus geothermalis and Arthrobacter globiformis, were selected for further investigation ([0076]-[0081]).
Hoffman et al. (US PGPub No. 20190309269, which correlates to WO 2019183292, of record) pertains to erythroid cells that have been engineered to comprise a uricase (Title, Abstract). Hoffman teaches that uricases are known to the art, including ones from Candida utilis, Aspergillus flavus, Penicillium freii, Aspergillus niger, Schizosaccharomyces pombe (Fission yeast), Schizosaccharomyces pombe (Fission yeast), Arthrobacter globiformi, Bacillus subtilis, Cellulomonas flavigena, Mus musculus, Danio rerio, Macaca mulatta, Glycine max, Oryza sativa subsp. japonica, and Drosophila melanogaster ([0015]; [0141], Table 1). However, no clear correlation between a defined structure and the functions of the entire genus is contemplated therein. Further, Fig. 1 of Hoffman demonstrates varying levels of activity among uricase from different species.
Thus, there is no evidence of a clear correlation between structure and function in the art.
Therefore, in light of the guidance and examples in the specification, taking into account the general knowledge in the art, one having ordinary skill in the art around the time of filing would have concluded that the specification demonstrated possession of a fusion protein comprising uricase having the sequence set forth in SEQ ID NO: 9 or SEQ ID NO:10, but one would not have concluded that this single species of the fusion protein comprises a “representative number of species” within the claimed genus of any such enzyme.
For these reasons, the disclosure fails to provide adequate written description to support the entirety of the broad genus claim to any and all uricase fusion proteins.
Claims 1-4 and 9 are thus rejected under 35 U.S.C. § 112(a) because the claimed subject matter is not described in the specification in such a way as to reasonably convey to a skilled artisan that the inventor, or a joint inventor, had possession of the 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.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-4 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Hudalla et al. (US PGPUB No. 20180044379, hereafter “Hudalla”) and Baca et al. (US PGPub No. 20180258406, hereafter “Baca”).
Hudalla teaches a set of charge complementary self-assembling peptides comprising a positive peptide comprising at least 3 amino acids (A1-A3, as set forth sequentially from C to N terminus), wherein A1, A2, and A3 are each independently selected from a positively charged amino acid and a hydrophobic amino acid, and wherein at least one amino acid of A1-A3 is a positively charged amino acid and at least one amino acid of A1-A3 is a hydrophobic amino acid; and a negative peptide comprising at least 3 amino acids (B1-B3), wherein B1, B2, and B3 are each independently selected from a negatively charged amino acid and a hydrophobic amino acid, and wherein at least one amino acid of B1-B3 is a negatively charged amino acid and at least one amino acid of B1-B3 is a hydrophobic amino acid, wherein the positive and the negative peptide are configured to self-assemble when mixed under a stimulating condition (Abstract, claim 1, [0005]) and discloses that the positive peptide has a sequence selected from the group consisting of SEQ ID NO: 1, 3, 5, 6, or 8, which are identical to the amino acid sequences of the positive peptides in the instant claims.
Hudalla teaches a fusion peptide containing a cargo polypeptide produced from a recombinant DNA construct containing DNA encoding the negative or positive peptide segment operatively coupled with DNA encoding the cargo polypeptide and any optional linker and that the cargo polypeptide may include, inter alia, an enzyme or a pharmaceutically relevant protein- a protein that can be effective to prevent or treat a disease or symptom thereof in a subject ([0079]).
Regarding claims 2-3 and 9, Hudalla teaches that the positive peptide, the negative peptide, or the positive and the negative peptide can each further include one or more cargo polypeptides coupled to the N-terminus, the C terminus, or both the N-terminus and the C-terminus of the positive peptide, the negative peptide, or both the positive and the negative peptide ([0008]; claim 9). Hudalla does not explicitly teach that the peptide is “between” the N- and C-terminus of one or more of the peptides, however, FIG. 49 (reproduced below) demonstrates an exemplary molecule having multiple CATCH peptides with peptide linkers and TEV sites between each, while FIG. 50B demonstrates an corresponding amino acid sequence.
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FIG. 49 from Hudalla et al.
Regarding claim 4, Hudalla teaches that the fusion protein may be used in pharmaceutical formulations and/or incorporated into other compositions ([0102] and [0146]).
Hudalla also teaches that the self-assembly domains/peptides can be engineered to resist assembly until acted upon by a stimulus that can be applied under neutral, near-physiological conditions that support maintaining protein folding and function, which has advantages for fusion protein assembly and precision of control during production ([0122]-[0125]). Hudalla teaches that such “charge-complementary peptides can contain one or more ionizable residues that renders the self-assembly of the charge-complementary peptides energetically unfavorable until the two peptides are combined in solution” ([0124]). Hudalla also teaches that “CATCH peptides were designed to co-assemble into β-sheet nanofibers when combined, yet resist self-assembly due to electrostatic repulsion. This electrostatically controlled assembly enabled high yield production” ([0224]). Hudalla suggests that stable integration of folded proteins into supramolecular assemblies is broadly useful for creating biomaterials with more sophisticated functional capabilities and that such a self-assembling system is useful in addressing the impending functionality bottleneck imposed by continued reliance on unfolded peptides and small organic compounds as functional components within biomaterials ([0224]).
However, Hudalla does not explicitly teach a fusion protein wherein either the positive and/or negative peptide is attached to a uricase protein.
Baca et al. teaches improved uricase sequences having beneficial effects and methods of treating patients suffering from hyperuricemia (Title, Abstract).
Baca teaches that urate oxidase, or uricase (EC 1.7.3.3, uox) is a homotetrameric enzyme composed of four identical 34 KDa subunits which is responsible for the initial step that begins a series of reactions that convert uric acid to a more soluble and easily excreted product ([0035]).
Baca states that “in humans and some primates uricase is not expressed. The lack of uricase expression in humans has resulted in higher systemic uric acid levels, and in some cases, hyperuricemia conditions such as gout and tumor lysis syndrome.” ([0004]). Baca teaches two clinically approved uricases, Krystexxa® and Elitek®, each of which have adverse side effects, and teaches that both are subject to a black box warning for anaphylaxis, infusion reactions, and/or hemolysis ([0008]-[0010]). Thus, Baca teaches that there is a need in the art to develop safer, more convenient, and less immunogenic options for treating hyperuricemia (e.g. and unmet problem to be solved) ([0010]-[0011]).
Baca also teaches methods for preparing recombinant uricases ([0066]) and teaches that uricase are oligomeric proteins, particularly that they form tetramers ([0067]-[0068]; FIG ).
Baca teaches that uricase enzymes were modified and optimized, and that more than 200 uricase sequences from publicly-available databases were studied, from which 8 candidate sequences were chosen for further investigation and optimization ([0074]-[0076]). Baca goes on to demonstrate that most of the tested uricases were present at high level in the insoluble (P) material, and not easily produced in soluble form ([0076]; FIG. 1).
Therefore, before the effective filing date of the instant invention, to one of ordinary skill in the art, it would have been obvious to combine the one or more of the charged complementary self-assembling peptides taught in Hudalla with a uricase enzyme as taught in Baca for the benefit of producing a controllable, self-assembling complex having a therapeutically useful uricase, taught in Baca to be desirable for treating diseases caused by uric acid build-up, where the uricase enzyme is ready for improvement because of the known problems with solubility and adverse effects.
One would have been motivated to do so from the teachings of both Baca and Hudalla, namely that uricase has potential valuable therapeutic use but known preparations of it suffer from the problems of adverse side-effects and production issues due to insolubility and the large molecular weight of its tetramer form, as taught in Baca. Hudalla teaches a controllable way to produce and oligomerize cargo proteins, by linking a desired protein (or fragments of it) to the charged complementary self-assembling peptides, and being able to selectively control when the proteins become active and control precisely the oligomerization status, through the charged peptide interactions. Thus, one would reasonably predict that subunits and/or fragments of uricase fused to the charged complementary self-assembling peptides of Hudalla would result in improved production, due to changes in the solubility of the fused peptide as suggested by Hudalla, and would result in control of the tetramer/oligomer state of the uricase subunits, that would result in improved therapeutic formulations.
MPEP § 2143.I. KSR Rationale (A) describes that it is obvious to combine prior art elements according to known methods to yield predictable results: “The rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395... "[I]t can be important to identify a reason that would have prompted a person of ordinary skill in the relevant field to combine the elements in the way the claimed new invention does." KSR, 550 U.S. at 418, 82 USPQ2d at 1396”.
In the instant case as discussed above each of the recited elements of the claimed invention was known to the prior art, as the charged complementary self-assembling peptides are described in detail in Hudalla ’379 and recombinant uricase enzymes are taught in Baca ’406. Further, one would reasonably predict that fusion of uricase to the charged complementary self-assembling peptides of Hudalla would result in improved production, and better enzyme kinetics with control of the tetramer/oligomer state, as discussed above.
Regarding claims 2, 3, and 9, it would have been prima facie obvious and within the level of ordinary skill in the art to produce fusion proteins with the cargo protein attached at either end, or fused in an internal sequence, of the charged complementary self-assembling peptides as this is taught in Hudalla. Such recombinant molecular biology techniques are well-known and routine in the biochemical arts. Further, there is no evidence of unexpected results or criticality of any one of these arrangements, as all three options (N-terminus fusion, C-terminus fusion, and internal or “in between” arrangements) are taught in the instant disclosure and claimed interchangeably. Thus, it would have been a matter of routine optimization for one in ordinary skill to produce the instantly claimed fusion proteins in any such arrangement.
In view of the evidence and teachings of the cited art, there would have existed a reasonable expectation of success, because Hudalla teaches fusion proteins with charged complementary self-assembling peptides and teaches that cargo proteins, including enzymes, may be attached thereto, while Baca teaches the known applications and optimization of uricase enzymes. As both references support that molecular cloning and production of recombinant protein sequences is within the level of ordinary skill and common to the art, the production of such fusion proteins would have been reasonably successful.
Therefore, the invention of claims 1-4 and 9, as a whole would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
Claims 1-4 and 9 are rejected.
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDREW TERRY MOEHLMAN whose telephone number is (571)270-0990. The examiner can normally be reached M-F 9am-5pm EST.
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/A.T.M./Examiner, Art Unit 1655
/ANAND U DESAI/Supervisory Patent Examiner, Art Unit 1655