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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 7/8/2026 was filed after the mailing date of the non-final rejection on 4/8/2026. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Response to Amendment
Applicant’s remarks and amendments filed 7/8/2026, in response to the non-final rejection mailed 4/8/2026, are acknowledged and have been fully considered.
Any previous rejection or objection not mentioned herein is withdrawn.
Applicant’s amendment to the claims is acknowledged. This listing of the claims replaces all prior versions and listings of the claims.
Claims 1-22 are pending. Claims 14-22 are newly added. Claims 5-8 and 10-13 remain withdrawn as being directed to non-elected inventions.
Claims 1-4, 9, 14-22 and have been examined on the merits.
Applicant’s arguments, see pages 8-9 of the remarks filed 7/8/2026, with respect to the description of the claims under 35 U.S.C. § 112(a) for lack of Written Description have been fully considered and are persuasive. Applicant indicates that the term “uricase” refers to an art-recognized structurally characterized enzyme family, by which the instant claims are limited, and that there exists a recognized correlation between sequence/structure and function. The rejection of claims 1-4 and 9 under 35 U.S.C. § 112(a) has thus been withdrawn.
Claim Objections
Claim 15 is objected to because of the following informalities:
Claim 15 recites the limitation “the negative peptide comprises SEQ ID NO: 9”. For increased clarity and consistency of the language in the claims, it is recommended to amend the claim to recite: “the negative peptide comprises the amino acid sequence of SEQ ID NO: 9”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
(Modified and/or New, due to Applicant’s amendments)
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, 9, 14, and 17-22 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 3-4, 9, 14, and 17-22 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 by recitation of a particular amino acid sequence. 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?
It is noted that claims 15 and 16 recite specific amino acid sequences that give definition by structure to the “negative peptide”.
All other claims depend directly or indirectly from the rejected claim 1 and are, 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.
Additionally, new Claim 20 recites, in line 2, “under physiological conditions”. There is no special definition provided for “physiological conditions” in the instant disclosure and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. What temperature is required for this stability? As an example of the ambiguity, human physiological conditions would be different than those of unicellular organisms such as yeast. Further, it is presumed from the specification that there is a neutral pH, but there is no clear definition for what range of pH or temperature variance is acceptable and still be considered a “physiological condition”. Because one cannot accurately determine the metes and bounds of the conditions for which the composition is to be stable, the resulting claim is indefinite.
Response to Arguments
Applicant’s argues that the amendment to claim to recite that the negative peptide optionally further comprises one or more additional amino acid residues at the N-terminus or C-terminus or both the N-terminus and the C-terminus overcomes the rejection for indefiniteness described above. However, the amendment is an optional limitation, and therefore not required of the claim, thus it is not considered to practically limit the structure of the negative peptides.
The amended claim 1 fails to define a negative peptide such that one of ordinary skill in the art would be appropriately notified of the scope of the claim. There is no recitation of the conditions during which a negative peptide is determined. Charge at neutral pH is different than a peptide’s charge in a high pH or low pH buffer.
It is noted that claims 15 and 16 recite specific amino acid sequences that give definition by structure to the “negative peptide”. It appears that a negative peptide is adequately defined in the sequences found in SEQ ID NOs: 2 (which is also found on the N-terminus end of SEQ ID NO: 9), 4, and/or 7. However, the other claims are not limited by any specific sequence.
Therefore, the 112(b) rejection of claim 1, pertaining to the metes and bounds of the “negative peptide” limitation is maintained.
Claim Rejections - 35 USC § 103
(Modified due to Applicant’s amendments)
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, 9, and 16-22 are rejected under 35 U.S.C. 103 as being unpatentable over Hudalla et al. (US PGPUB No. 20180044379, hereafter “Hudalla”) in view of 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 a 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]).
Regarding newly added claims 16 and 17, Hudalla teaches that the negative peptide can have a sequence of SEQ ID NO: 2, 4, or 7 ([0008], claim 7), which appear to be essentially identical to the corresponding sequences recited herein.
Regarding claim 18, Hudalla teaches that the peptides can “further include one or more segments that each encode for a purification tag. Suitable purification tags are generally known in the art and can include, but are not limited to, FLAG, His tag, maltose binding protein, and glutathione-S-transferase.” ([0157]). Thus, the selection or choice of any of these purification tags, including many that are not His-tags are taught in Hudalla.
Regarding claims 19-20, Hudalla teaches that proteins produced with the CATCH- peptides can be induced to form a macroscopic hydrogel that maintains the desired structure of the attached proteins, e.g. maintains function (see [0201]-[0210]; [0216]-[0217]). Hudalla teaches that “these data demonstrated that a covalent fusion of a folded protein and a CATCH peptide was stably installed into CATCH hydrogels without appreciable loss of activity” in regard to the fusion protein containing GFP that was used as a proof-of-principle therein.
Regarding claims 21 and 22, Hudalla teaches combining the composition having positive and negative peptides with a suitable cargo peptide, with a pharmaceutically acceptable carrier or excipient, and/or a “pharmaceutically acceptable salt”, meaning an acid or base addition salt whose counter-ions are non-toxic to the subject to which they are administered in pharmaceutical doses of the salts. (see [0102]-[0104]).
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.
Regarding newly added claims 16 and 17, Hudalla teaches that the negative peptide can have a sequence of SEQ ID NO: 2, 4, or 7 and it would have been prima facie obvious to use any one or more of the negative peptides used successfully therein.
Regarding claim 18, Hudalla teaches that the selection or choice of many purification tags, including many that are not His-tags are taught in Hudalla. Because this is recited as a negative limitation, any and all possible combinations of the peptide that do not have a poly-His tag meet this limitation. It is evident from Hudalla that any of the articulated purification tags may be used and thus, following the combined teachings of Hudalla and Baca would have naturally led one of ordinary skill to a number of variants that do not include a poly-histidine tag.
Regarding claims 19-20, Hudalla teaches that proteins produced with the CATCH- peptides can be induced to form a macroscopic hydrogel that maintains the desired structure of the attached proteins, e.g. maintains function. Hudalla successfully demonstrates that a covalent fusion of a folded protein and a CATCH peptide was stably installed into CATCH hydrogels without appreciable loss of activity” in regard to the fusion protein containing GFP that was used as a proof-of-principle therein. One having ordinary skill in the art would have thus been motivated to generate a fusion protein of the useful uricase enzyme taught in Baca, with a reasonable expectation that the combination would have proper folding and activity. The testing under 72 hours amounts to a functional property that would naturally follow when producing a protein according to the teachings of the cited references. Applicant has not provided convincing evidence that there is a special property due to a particular combination (i.e. that this activity is only found in some specific combinations of sequences).
Regarding claims 21 and 22, Hudalla suggests combining the composition having positive and negative peptides with a useful cargo peptide with a pharmaceutically acceptable carrier or excipient, and/or a pharmaceutically acceptable salt. Such combinations are well-known in the art and amount to nothing more than optimization of the delivery mechanism and buffer for the peptides. One having ordinary skill in the art would have been well versed in the selection of proper carriers or excipient.
Regarding the delivery mechanism recited in claim 22, the high level recitation of “formulated for administration” does not require any actual structure for the composition. Thus, this amounts to a recitation of an intended use e.g. “for administration”. Because such formulations and preparations are well-known in the art, this cannot be considered to be an inventive property, especially because no particular structure is required. Regardless, the carriers, excipients, buffers, and/or a pharmaceutically acceptable salts taught in Hudalla would likely be suitable for such injection, if desired by one of ordinary skill in the art.
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, 9, and 16-22 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.
Response to Arguments
Applicant's arguments, in pages 8-11 of the remarks filed 7/8/2026, regarding the previous rejection of claims 1-4 and 9 as being obvious over the combined teachings of Hudalla et al. (US PGPUB No. 20180044379) and Baca et al. (US PGPub No. 20180258406) have been fully considered but they are not persuasive.
Applicant argues (see page 10) that there is no expectation that a uricase enzyme fused to a self-assembling peptide, or incorporated into an assembled supramolecular structure, will retain the catalytic activity and thus, one would not have been motivated to combine the therapeutic uricase of Baca with the complementary self-assembling peptides taught in Hudalla.
As an initial matter, the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
Additionally, MPEP § 2143.02.I. establishes that conclusive proof of efficacy is not required to show a reasonable expectation of success. OSI Pharm., LLC v. Apotex Inc., 939 F.3d 1375, 1385, 2019 USPQ2d 379681 (Fed. Cir. 2019) ("To be clear, we do not hold today that efficacy data is always required for a reasonable expectation of success. Nor are we requiring ‘absolute predictability of success.’"); Acorda Therapeutics, Inc. v. Roxane Lab., Inc., 903 F.3d 1310, 1333, 128 USPQ2d 1001, 1018 (Fed. Cir. 2018) ("This court has long rejected a requirement of ‘[c]onclusive proof of efficacy’ for obviousness." (citing to Hoffmann-La Roche Inc. v. Apotex Inc., 748 F.3d 1326, 1331 (Fed. Cir. 2014); PharmaStem Therapeutics, Inc. v. ViaCell, Inc., 491 F.3d 1342, 1364 (Fed. Cir. 2007); Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1364, 1367–68 (Fed. Cir. 2007) (reasoning that "the expectation of success need only be reasonable, not absolute")).
One of ordinary skill in the art would consider the teachings of Hudalla in its entirety. Hudalla describes a set of charge complementary peptides to be coupled to a cargo polypeptide that are capable of self-assembling under stimulating conditions (Abstract). Hudalla teaches that the complementary peptides can be capable of forming supramolecular structures, and teaches that the negative or positive peptide segment can be operatively coupled to the cargo polypeptide and any optional linker such that the cargo polypeptide is translated in-frame with negative or positive peptide segment (see e.g. [0079]). Hudalla describes that the cargo polypeptide can be a reporter protein (e.g. a fluorescent protein), a pharmaceutically relevant protein (a protein that can be effective to prevent or treat a disease or symptom thereof in a subject), and/or an enzyme, inter alia. It is evident from the disclosure of Hudalla that cargo peptides are intended to be fully interchangeable with the charge complementary self-assembling peptides taught therein.
Hudalla teaches successful integration of a test protein, GFP, which was able to form the correct folded structures necessary for its fluorescence (see especially [0216]-[0217]). Because Hudalla teaches applying the charged peptides for delivery of pharmaceutically relevant proteins and enzymes, there is nothing taught therein which would have led away from the instantly claimed invention. As discussed before, this amounts to a matter of judicious selection in providing a uricase known in the art as the pharmaceutically relevant protein/enzyme according to the teachings of Hudalla in view of Baca. In addition, the teachings of Baca that the Applicant point out indicate that one of ordinary skill in the art would know to considering these various factors involving enzyme stability and tetramerization when providing uricase for a therapeutic activity (see e.g. [0106] and [0076]), and the adjustment of such variable amounts to optimization when producing a fusion protein, according to the guidance in the art.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
The applicant argues that there is no indication in Baca that uricases could be incorporated into self-assembling peptides or hydrogels, and that Baca’s disclosure is evidence of uncertainty as to whether the claimed uricase fusion protein and hydrogel would function together. However, in response to this, it is noted that "A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton."KSR, 550 U.S. at 421, 82 USPQ2d at 1397. "[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle."Id. at 420, 82 USPQ2d at 1397. Office personnel may also take into account "the inferences and creative steps that a person of ordinary skill in the art would employ."Id. at 418, 82 USPQ2d at 1396. See MPEP 2141.II.C.
From the combined teachings of Hudalla and Baca, one of ordinary skill in the art would have been aware of the problems highlighted by the Applicant, which Baca teaches modifications to solve, and one would have been sufficiently motivated to optimize the selection of the enzyme and the conditions under which the fusion protein is produced and tested.
In response to Applicant’s argument regarding the solubility and recovery of untagged uricase, the Examiner does not find this argument persuasive in light of the knowledge in the art and the teachings of Hudalla. Tagging insoluble enzymes is an established strategy to increase solubility (e.g. this is often done using an MBP tag, for example). Further, the teachings of Hudalla establish that the tagging with the negative and/or positive peptides can be used to overcome such issues with solubility and to provide increased control as to when or even where such supermolecular assembly is desired (e.g. [0123]-[0124]). In other words, one would have predicted that tagging the uricase with the negative and/or positive peptides would result in improved control over the assembly process, as established by the teachings of Hudalla.
It is herein noted that the claims are directed to a product, i.e. the composition, and not to a method of producing the product or using the product. Because the teachings of the art would have motivated one to try the combination of the charged peptides from Hudalla with a uricase as suggested by Baca, one would have been motivated to produce a composition with the functional properties which Applicant is arguing.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971), and see MPEP § 2145.X.A: “there is no requirement that an "express, written motivation to combine must appear in prior art references before a finding of obviousness." Ruiz v. A.B. Chance Co., 357 F.3d 1270, 1276, 69 USPQ2d 1686, 1690 (Fed. Cir. 2004). See KSR, 550 U.S. at 402, 82 USPQ2d at 1389 ("The diversity of inventive pursuits and of modern technology counsels against confining the obviousness analysis by a formalistic conception of the words teaching, suggestion, and motivation, or by overemphasizing the importance of published articles and the explicit content of issued patents.") “.
Here, both the cited prior art references are reasonably pertinent to the problem at hand, and the combination of the therapeutically useful uricase enzyme, useful for the treatment of gout and other inflammatory conditions, with the charged complimentary self-assembling polypeptides taught in Hudalla with the stated goal of being used with, among several other cargo proteins, enzymes would have been a matter of combining elements already known in the art, according to the teachings therein. One of ordinary skill would predict from the teaching of Hudalla that therapeutically useful enzymes which require careful control of oligomerization to be activated, as is taught in Baca, would be suitable as cargo proteins.
Regarding Applicant arguments concerning the surprising enzymatic activity of a uricase fusion protein immobilized in the nanofiber hydrogel of [0322]-[0323] (e.g. FIG.s 56-57, and 59), and of the in vivo experiments discussed in [0326]-[0327] (FIG. 62), it is noted that these results pertain to only one particular species of the invention, one having a uricase from Aspergillus flavus fused to a negative peptide at the N-terminus of the uricase enzyme resulting in a fusion protein having the sequence of SEQ ID NO: 9 (FIG. 59). The evidence has been considered, however the claims at issue are not limited in scope to this one fusion protein, and thus, the evidence provided is not considered to be commensurate in scope with the argument set forth by the Applicant. Further, Applicant has not provided any convincing evidence of combinations of uricase enzymes and cargo peptides that lack activity, such that the enzyme activity could be considered an unexpected result nor is there suitable evidence that the art is unpredictable. Because the enzyme family is well-studied and structures of uricase enzymes are known (see Applicant’s discussion of the previous rejections under 112(a) on pages 8-9), this argument is not found convincing.
The rejections of claims 1-4 and 9 are thus maintained for the reasons described above. Further, the arguments above have also been considered regarding the application of the prior art to the limitations of the newly added claims. Claims 16-22 have been rejected under 35 U.S.C. § 103 as being obvious over the combination of Hudalla and Baca as described above.
Allowable Subject Matter
Claim 15 is 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.
The following is a statement of reasons for the indication of allowable subject matter:
Claim 15 appears to require a specific fusion protein that comprises the entirety of the amino acid sequence of SEQ ID NO: 9. Such a sequence is not expressly taught in the prior art, nor would this specific fusion protein have been obvious to one of ordinary skill in the art. SEQ ID NO: 9 contains, from amino acid 34 to amino acid 335, the amino acid sequence of a wild-type uricase protein found in Aspergillus flavus (see APPENDIX A below). The cited reference Baca et al. teaches that this uricase protein has undesirable properties for using for chronic treatment of gout. Therefore, one of ordinary skill in the art would not have possessed motivation to select and provide this specific amino acid sequence for the uricase when making a uricase fusion protein.
Applicant’s arguments on pages 10-11 concerning the expectation of success and the activity of the claimed invention involves data from a fusion protein which appears to be same as that recited in claim 15. Thus, the arguments presented there appear to be commensurate in scope with the fusion peptides of claim 15.
As allowable subject matter has been indicated, applicant's reply must either comply with all formal requirements or specifically traverse each requirement not complied with. See 37 CFR 1.111(b) and MPEP § 707.07(a).
Conclusion
Claims 1-4, 9, 14, and 16-22 are rejected.
Claim 15 is presently objected to but would allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims, and to address the informality identified above.
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 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
APPENDIX A: Alignment of SEQ ID NO: 9 to B8NB34 (Uricase from Aspergillus flavus)
Qy = SEQ ID NO: 9
Db = B8NB34_ASPFN (UniProt), Uricase from Aspergillus flavus
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