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 .
Detailed Action
Applicant’s election of Group I, claims 1-15 without traverse in the reply filed on 09/24/2026 is acknowledged. Claims 1-20 are pending in this application; Group I, claims 1-15 reading on the elected invention is now under consideration for examination; non-elected Groups’ II-III, claims 16-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Priority
Applicants’ claim for the benefit of priority under 35 U.S.C. 119(e) is acknowledged. This application claims the benefit of priority under 35 U.S.C. 119(e) to the US Provisional applications: 63/695,203 filed on 09/16/2024 and 63/592,133 filed on 10/20/2023; please note claims 13-15 comprising the amino acid sequences of SEQ ID NOs: 1-3 are only granted the priority date of instant application filed on 10/20/2024, as said sequences SEQ ID NOs: 1-3 were first disclosed in the instant application filed on 10/20/2024.
Specification-Objection
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. The specification contains hyperlinks to various site domains, for example, ¶ [0070], page 21 of the instant application. Applicants’ are required to thoroughly scrutinize the specification and delete all embedded hyperlink and/or other form of browser-executable code. See MPEP § 608.01. Appropriate correction is required.
Claims Objections
Claims 13-15 are objected to, due to the following informality: Claims 13-15 recites the phrase “… an amino acid sequence of SEQ ID NO: 3, 2 and 1” respectively, as such, given that the claim language recites “an amino acid sequence”, it is deemed to encompass and read on polypeptides comprising “any two/dipeptide sequences of SEQ ID NO: 1, 2, and 3 and having the recited activity. Examiner suggests amending the claims to recite “the amino acid sequence”. Appropriate correction is required. For examination purposes claims 13-15 are interpreted to encompass variants and mutants of the recited sequence(s).
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 13-15 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 pre-AIA the applicant regards as the invention.
Claims 13-15 recites the phrase “… an amino acid sequence of SEQ ID NO: 3, 2 and 1” respectively, as such, given that the claim language recites “an amino acid sequence”, it is deemed to encompass and read on polypeptides comprising “any two/dipeptide sequences of SEQ ID NO: 1, 2 and 3 and having the recited activity.. Examiner suggests amending the claim to recite “the amino acid sequence”. Appropriate correction is required. For examination purposes claims 13-15 are interpreted to encompass variants and mutants of the recited sequence(s). The scope of the claims are unclear, as such it is unclear how homologous/identical to the amino acid sequences of SEQ ID NOs: 1, 2 and 3; a sequence of interest must be to be included within the scope of the claims and furthermore, it is not clear whether a full-length or a partial fragments of SEQ ID NOs: 1, 2 and 3 is encompassed within the scope of the claims.
Claim Rejections: 35 USC § 112(a)
The following is a quotation 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.
Written Description
I. Claims 1-15 are rejected under 35 U.S.C. (a) or 35 U.S.C. 112, first paragraph, as containing 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(s), at the time the application was filed, had possession of the claimed invention.
Claims 1-15 of the instant application as interpreted are directed to a genus of polypeptides with the associated function comprising undefined and unlimited structures i.e., composition comprising an exosome and an arginase, wherein the arginase is fused to a tetraspanin, wherein tetraspanin is a CD9 or fragment thereof (as in claims 1-12; no specific structure is recited for the claimed arginase, tetraspanin and CD9 or fragment thereof); and to a genus of polypeptides i.e., having an amino acid sequence of SEQ ID NOs: 1-3 having arginase activity, as such, the term “an amino acid sequence” in broadest reasonable interpretation encompasses not only SEQ ID NOs: 1, 2 and 3 but any fragment/subsequence within SEQ ID NOs: 1, 2 and 3 due to the recitation of indefinite article “an”; given that the claim language recites “an amino acid sequence”, it is deemed to encompass and read on “any two/dipeptide sequences of SEQ ID NOs: 1, 2 and 3 (as in claims 13-15; also see claims objections and 35 U.S.C. 112(b), rejection above for claim interpretation).
In University of California v. Eli Lilly & Co., 43 USPQ2d 1938, the Court of Appeals for the Federal Circuit has held that “A written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula, [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials”. As indicated in MPEP § 2163, 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, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show that Applicant was in possession of the claimed genus. In addition, MPEP § 2163 states that a representative number of species means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
In the instant case, there is no structure associated with function with regard to a genus of polypeptides with the associated function comprising undefined and unlimited structures i.e., composition comprising an exosome and an arginase, wherein the arginase is fused to a tetraspanin, wherein tetraspanin is a CD9 or fragment thereof (as in claims 1-12; no specific structure is recited for the claimed arginase, tetraspanin and CD9 or fragment thereof); and to a genus of polypeptides i.e., having an amino acid sequence of SEQ ID NOs: 1-3 having arginase activity, as such, the term “an amino acid sequence” in broadest reasonable interpretation encompasses not only SEQ ID NOs: 1, 2 and 3 but any fragment/subsequence within SEQ ID NOs: 1, 2 and 3 due to the recitation of indefinite article “an”; given that the claim language recites “an amino acid sequence”, it is deemed to encompass and read on “any two/dipeptide sequences of SEQ ID NOs: 1, 2 and 3 (as in claims 13-15; also see claims objections and 35 U.S.C. 112(b), rejection above for claim interpretation).
No information, beyond the characterization of specific compositions with defined structures i.e., comprising the amino acid sequences of SEQ ID NOs: 1-3 (see ¶ [0084]; pages 26-27 of specification), has been provided by the applicants’, which would indicate that they had possession of the claimed members of the genus of polypeptides with the associated function comprising undefined and unlimited structures i.e., composition comprising an exosome and an arginase, wherein the arginase is fused to a tetraspanin, wherein tetraspanin is a CD9 or fragment thereof (as in claims 1-12; no specific structure is recited for the claimed arginase, tetraspanin and CD9 or fragment thereof); and to a genus of polypeptides i.e., having an amino acid sequence of SEQ ID NOs: 1-3 having arginase activity, as such, the term “an amino acid sequence” in broadest reasonable interpretation encompasses not only SEQ ID NOs: 1, 2 and 3 but any fragment/subsequence within SEQ ID NOs: 1, 2 and 3 due to the recitation of indefinite article “an”; given that the claim language recites “an amino acid sequence”, it is deemed to encompass and read on “any two/dipeptide sequences of SEQ ID NOs: 1, 2 and 3 (as in claims 13-15; also see claims objections and 35 U.S.C. 112(b), rejection above for claim interpretation).
The genus of polypeptides comprising undefined and unlimited structures i.e., a genus of polypeptides required in the claimed invention is an extremely large structurally and functionally variable genus. While the argument can be made with the characterization of specific compositions with defined structures i.e., comprising the amino acid sequences of SEQ ID NOs: 1-3 (see ¶ [0084]; pages 26-27 of specification), since one could use structural homology to isolate or identify those polypeptides with the desired activity recited in the claims. The art clearly teaches the “Practical Limits of Function Prediction”: (a) Devos et al., (Proteins: Structure, Function and Genetics, 2000, Vol. 41: 98-107), teach that the results obtained by analyzing a significant number of true sequence similarities, derived directly from structural alignments, point to the complexity of function prediction. Different aspects of protein function, including (i) enzymatic function classification, (ii) functional annotations in the form of key words, (iii) classes of cellular function, and (iv) conservation of binding sites can only be reliably transferred between similar sequences to a modest degree. The reason for this difficulty is a combination of the unavoidable database inaccuracies and plasticity of proteins (Abstract, page 98) and the analysis poses interesting questions about the reliability of current function prediction exercises and the intrinsic limitation of protein function prediction (Column 1, paragraph 3, page 99) and conclude that “Despite widespread use of database searching techniques followed by function inference as standard procedures in Bioinformatics, the results presented here illustrate that transfer of function between similar sequences involves more difficulties than commonly believed. Our data show that even true pair-wise sequence relations, identified by their structural similarity, correspond in many cases to different functions (column 2, paragraph 2, page 105).
(b) Whisstock et al., (Quarterly Reviews of Biophysics 2003, Vol. 36 (3): 307-340) also highlight the difficulties associated with “Prediction of protein function from protein sequence and structure”; “To reason from sequence and structure to function is to step onto much shakier ground”, closely related proteins can change function, either through divergence to a related function or by recruitment for a very different function, in such cases, assignment of function on the basis of homology, in the absence of direct experimental evidence, will give the wrong answer (page 309, paragraph 4), it is difficult to state criteria for successful prediction of function, since function is in principle a fuzzy concept. Given three sequences, it is possible to decide which of the three possible pairs is most closely related. Given three structures, methods are also available to measure and compare similarity of the pairs. However, in many cases, given three protein functions, it would be more difficult to choose the pair with most similar function, although it is possible to define metrics for quantitative comparisons of different protein sequences and structures, this is more difficult for proteins of different functions (page 312, paragraph 5), in families of closely related proteins, mutations usually conserve function but modulate specificity i.e., mutations tend to leave the backbone conformation of the pocket unchanged but to affect the shape and charge of its lining, altering specificity (page 313, paragraph 4), although the hope is that highly similar proteins will share similar functions, substitutions of a single, critically placed amino acid in an active-site residue may be sufficient to alter a protein’s role fundamentally (page 323, paragraph 1).
(c) This finding is reinforced in the following scientific teachings and the art also teaches, even highly structurally homologous polypeptides do not necessarily share the same function and conversely functionally similar molecules do not necessarily have similar structures. For example proteins having similar structure have different activities; Witkowski et al., (Biochemistry 38:11643-11650, 1999) teaches that one conservative amino acid substitution transforms a b-ketoacyl synthase into a malonyl decarboxylase and completely eliminates b-ketoacyl synthase activity. Similarly, Wishart et al., (J. Biol. Chem., 1995, Vol. 270(10): 26782-26785) teach that a single mutation converts a novel phosphotyrosine binding domain into a dual-specificity phosphatase. The art also teaches that functionally similar molecules have different structures; Kisselev L., (Structure, 2002, Vol. 10: 8-9) teach that polypeptide release factors in prokaryotes and eukaryotes have same function but different structures.
As stated above, no information beyond the characterization of specific compositions with defined structures i.e., comprising the amino acid sequences of SEQ ID NOs: 1-3 (see ¶ [0084]; pages 26-27 of specification), has been provided by the applicants’, which would indicate that they had possession of the claimed genus of polypeptides with the associated function comprising undefined and unlimited structures i.e., composition comprising an exosome and an arginase, wherein the arginase is fused to a tetraspanin, wherein tetraspanin is a CD9 or fragment thereof (as in claims 1-12; no specific structure is recited for the claimed arginase, tetraspanin and CD9 or fragment thereof); and to a genus of polypeptides i.e., having an amino acid sequence of SEQ ID NOs: 1-3 having arginase activity, as such, the term “an amino acid sequence” in broadest reasonable interpretation encompasses not only SEQ ID NOs: 1, 2 and 3 but any fragment/subsequence within SEQ ID NOs: 1, 2 and 3 due to the recitation of indefinite article “an”; given that the claim language recites “an amino acid sequence”, it is deemed to encompass and read on “any two/dipeptide sequences of SEQ ID NOs: 1, 2 and 3 (as in claims 13-15; also see claims objections and 35 U.S.C. 112(b), rejection above for claim interpretation). As the claimed genera of polypeptides having widely variable structure and associated function, since minor changes in structure may result in changes affecting function and no additional information (species/variant/mutant/homologs) correlating structure with function has been provided. Furthermore, “Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features” (See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895).
Therefore, one skilled in the art cannot reasonably conclude that applicant had possession of the claimed invention at the time the instant application was filed. Applicants are referred to the revised guidelines concerning compliance with the written description requirement of 35 U.S.C. (a) or 35 U.S.C. 112, first paragraph, published in the Official Gazette and also available at www.uspto.gov.
Enablement
II. Claims 1-15 are rejected under 35 U.S.C. (a) or 35 U.S.C. 112, first paragraph, because the specification is enabling for the characterization of specific compositions with defined structures i.e., comprising the amino acid sequences of SEQ ID NOs: 1-3 (see ¶ [0084]; pages 26-27 of specification). However, specification does not reasonably provide enablement for members of the genus of polypeptides with the associated function comprising undefined and unlimited structures i.e., composition comprising an exosome and an arginase, wherein the arginase is fused to a tetraspanin, wherein tetraspanin is a CD9 or fragment thereof (as in claims 1-12; no specific structure is recited for the claimed arginase, tetraspanin and CD9 or fragment thereof); and to a genus of polypeptides i.e., having an amino acid sequence of SEQ ID NOs: 1-3 having arginase activity, as such, the term “an amino acid sequence” in broadest reasonable interpretation encompasses not only SEQ ID NOs: 1, 2 and 3 but any fragment/subsequence within SEQ ID NOs: 1, 2 and 3 due to the recitation of indefinite article “an”; given that the claim language recites “an amino acid sequence”, it is deemed to encompass and read on “any two/dipeptide sequences of SEQ ID NOs: 1, 2 and 3 (as in claims 13-15; also see claims objections and 35 U.S.C. 112(b), rejection above for claim interpretation). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands (858 F.2d 731, 8 USPQ 2nd 1400 (Fed. Cir. 1988)) as follows: (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claim(s).
Claims 1-15 are so broad as to encompass: a genus of polypeptides with the associated function comprising undefined and unlimited structures i.e., composition comprising an exosome and an arginase, wherein the arginase is fused to a tetraspanin, wherein tetraspanin is a CD9 or fragment thereof (as in claims 1-12; no specific structure is recited for the claimed arginase, tetraspanin and CD9 or fragment thereof); and to a genus of polypeptides i.e., having an amino acid sequence of SEQ ID NOs: 1-3 having arginase activity, as such, the term “an amino acid sequence” in broadest reasonable interpretation encompasses not only SEQ ID NOs: 1, 2 and 3 but any fragment/subsequence within SEQ ID NOs: 1, 2 and 3 due to the recitation of indefinite article “an”; given that the claim language recites “an amino acid sequence”, it is deemed to encompass and read on “any two/dipeptide sequences of SEQ ID NOs: 1, 2 and 3 (as in claims 13-15; also see claims objections and 35 U.S.C. 112(b), rejection above for claim interpretation). The scope of the claims is not commensurate with the enablement provided by the disclosure with regard to the extremely large number of polypeptides broadly encompassed by the claims. Since the amino acid sequence of a protein encoded by a polynucleotide determines its structural and functional properties, predictability of which changes can be tolerated in a protein's amino acid sequence and obtain the desired activity requires a knowledge of and guidance with regard to which amino acids in the protein's sequence and the respective codons in its polynucleotide, if any, are tolerant of modification and which are conserved (i.e., expectedly intolerant to modification), and detailed knowledge of the ways in which the encoded proteins' structure relates to its function. However, in this case the disclosure is limited to characterization of specific compositions with defined structures i.e., comprising the amino acid sequences of SEQ ID NOs: 1-3 (see ¶ [0084]; pages 26-27 of specification). It would require undue experimentation of the skilled artisan to make and use the claimed genus of polypeptides with the associated function comprising undefined and unlimited structures i.e., composition comprising an exosome and an arginase, wherein the arginase is fused to a tetraspanin, wherein tetraspanin is a CD9 or fragment thereof (as in claims 1-12; no specific structure is recited for the claimed arginase, tetraspanin and CD9 or fragment thereof); and to a genus of polypeptides i.e., having an amino acid sequence of SEQ ID NOs: 1-3 having arginase activity, as such, the term “an amino acid sequence” in broadest reasonable interpretation encompasses not only SEQ ID NOs: 1, 2 and 3 but any fragment/subsequence within SEQ ID NOs: 1, 2 and 3 due to the recitation of indefinite article “an”; given that the claim language recites “an amino acid sequence”, it is deemed to encompass and read on “any two/dipeptide sequences of SEQ ID NOs: 1, 2 and 3 (as in claims 13-15; also see claims objections and 35 U.S.C. 112(b), rejection above for claim interpretation). The specification provides no guidance with regard to the making of variants and mutants or with regard to other uses as claimed in the instant claims. In view of the great breadth of the claims, amount of experimentation required to make and use the claimed polypeptides, the lack of guidance, working examples, and unpredictability of the art in predicting function from a polypeptide primary structure (for example, see Whisstock et al., Prediction of protein function from protein sequence and structure. Q Rev Biophys. 2003, Aug. 36 (3): 307-340), the claimed invention would require undue experimentation. As such, the specification fails to teach one of ordinary skill how to use the full scope of the polypeptides and the encoding polynucleotides encompassed by these claims.
While enzyme isolation techniques, recombinant and mutagenesis techniques are known, and it is not routine in the art to screen for multiple substitutions or multiple modifications as encompassed by the instant claims, the specific amino acid positions within a protein's sequence where amino acid modifications can be made with a reasonable expectation of success in obtaining the desired activity/utility are limited in any protein and the result of such modifications is unpredictable. In addition, one skilled in the art would expect any tolerance to modification for a given protein to diminish with each further and additional modification, e.g. multiple substitutions.
The specification does not support the broad scope of the claims which encompass: genus of polypeptides with the associated function comprising undefined and unlimited structures i.e., composition comprising an exosome and an arginase, wherein the arginase is fused to a tetraspanin, wherein tetraspanin is a CD9 or fragment thereof (no specific structure is recited for the claimed arginase, tetraspanin and CD9 or fragment thereof); and to a genus of polypeptides i.e., having an amino acid sequence of SEQ ID NOs: 1-3 having arginase activity, as such, the term “an amino acid sequence” in broadest reasonable interpretation encompasses not only SEQ ID NOs: 1, 2 and 3 but any fragment/subsequence within SEQ ID NOs: 1, 2 and 3 due to the recitation of indefinite article “an”; given that the claim language recites “an amino acid sequence”, it is deemed to encompass and read on “any two/dipeptide sequences of SEQ ID NOs: 1, 2 and 3 (also see claims objections and 35 U.S.C. 112(b), rejection above for claim interpretation), as claimed in claims 1-15, because the specification does not establish: (A) a rational and predictable scheme for identifying an enzyme of undefined and unlimited structural features exhibiting desired activity and with an expectation of obtaining the desired biological function; (B) defined core regions/motifs involved in the desired catalytic activity of encoded polypeptides; (C) the tertiary structure of the molecule and folding patterns that are essential for the desired activity and tolerance to modifications; and (D) the specification provides insufficient guidance as to which of the essentially infinite possible choices is likely to be successful.
Thus, applicants’ have not provided sufficient guidance to enable one of ordinary skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claims broadly including a genus of polypeptides with the associated function comprising undefined and unlimited structures i.e., composition comprising an exosome and an arginase, wherein the arginase is fused to a tetraspanin, wherein tetraspanin is a CD9 or fragment thereof (as in claims 1-12; no specific structure is recited for the claimed arginase, tetraspanin and CD9 or fragment thereof); and to a genus of polypeptides i.e., having an amino acid sequence of SEQ ID NOs: 1-3 having arginase activity, as such, the term “an amino acid sequence” in broadest reasonable interpretation encompasses not only SEQ ID NOs: 1, 2 and 3 but any fragment/subsequence within SEQ ID NOs: 1, 2 and 3 due to the recitation of indefinite article “an”; given that the claim language recites “an amino acid sequence”, it is deemed to encompass and read on “any two/dipeptide sequences of SEQ ID NOs: 1, 2 and 3 (as in claims 13-15; also see claims objections and 35 U.S.C. 112(b), rejection above for claim interpretation). The scope of the claim must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1975)). Without sufficient guidance, determination of polypeptides/enzymes having the desired biological characteristics is unpredictable and the experimentation left to those skilled in the art is unnecessarily, and improperly, extensive and undue. See In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988).
Although the claims are examined in the light of the specification, specification cannot be read into the claims, i.e., the limitations of the specification cannot be read into the claims (see MPEP 2111 R-5).
Claim Rejections: 35 USC § 102 (AIA )
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
I. Claims 1-12 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Hean et al., (US 2021/0386868 A1).
Hean et al., (US 2021/0386868 A1).disclose fusion proteins compositions comprising an exosome and an arginase and fused to tetraspanin; invention relates to engineered extracellular vesicles (EVs) as a novel therapeutic approach to treating urea cycle disorders; more specifically, the invention relates to the use of various protein engineering and nucleic acid engineering strategies for improving loading of urea cycle proteins or nucleic acids encoding urea cycle proteins into EVs and targeting of the resultant EVs to tissues and organs of interest (see Abstract; Fig. 1-2; and entire document); Urea cycle disorders (UCD) are genetic errors of metabolism caused by a deficiency in enzymes or mitochondrial transport proteins involved in the production of urea, resulting in accumulation of toxic levels of ammonia in the blood (hyperammonemia), the most common urea cycle disorders are: N-Acetylglutamate synthase deficiency, Carbamoyl phosphate synthetase deficiency; Ornithine transcarbamoylase deficiency; Citrullinemia (deficiency of argininosuccinic acid synthase); Argininosuccinic aciduria (deficiency of argininosuccinic acid lyase); Argininemia (deficiency of arginase) (¶ [0003-0014]); advantageous fusion protein constructs include the following non-limiting examples: CD63-PUF531, CD63-PUF×2, CD63-PUFengineered (alternatively known a PUFeng or PUF mRNA loc), CD81-PUF531, CD81-PUF×2, CD81-PUFengineered, CD9-PUF531, CD9-PU×2, CD9-PUFengineered, and other transmembrane-based fusion proteins, preferably based on tetraspanin exosomal proteins fused to one, two or more PUF proteins; advantageous fusion proteins comprising PUF proteins and at least one soluble exosomal protein include the following non-limiting examples: CD63-PUF, syntenin-PUF531, syntenin-PU×2, syntenin-PUFengineered, syndecan-PUF531, syndecan-PU×2, syndecan-PUFengineered, Alix-PUF531, Alix-PU×2, Alix-PUFengineered, as well as any other soluble exosome protein fused to a PUF protein (¶ [0072]).
Therefore, claims 1-12 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Hean et al., (US 2021/0386868 A1) and is deemed to anticipate claims 1-12 as written and when given the broadest reasonable interpretation.
II. Claims 1-12 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Liang et al., (US 2023/0301926 A1; priority 07/03/2020).
Liang et al., (US 2023/0301926 A1; priority 07/03/2020) disclose fusion proteins compositions comprising an exosome and an arginase and fused to tetraspanin (see Abstract; Fig. 18; and entire document); therapeutic protein cargos selected from the group comprising enzymes associated with urea cycle disorders including: N-acetylglutamate synthase, carbamoyl phosphate synthetase, ornithine transcarbamoylase (OTC), argininosuccinic acid synthase, argininosuccinic acid lyase, arginase, mitochondrial ornithine transporter, citrin, y+L amino acid transporter 1 and uridine monophosphate synthase (UMPS) (¶ [0075], [0141]); particularly advantageous EV proteins include tetraspanins, CD63, CD81, CD9 (¶ [0052]-0053], [0092], [0098], [0104]; and Claims); in another embodiment, the ABD may be fused to the N terminal domain (NTD) or C terminal domain (CTD) of the EV protein; and in another embodiment, the EVs of the present invention comprise additional sequences or domains within the ABD EV protein fusion protein construct; in one advantageous embodiment, the ABD EV protein further comprises at least one multimerization domain (¶ [0054-0060]); in certain embodiments, the therapeutic cargo is actively loaded into the ABD EVs of the present invention by the use of fusion proteins; in this case, the therapeutic cargo carried by the EV forms part of the EV protein-ABD fusion protein or alternatively the therapeutic cargo carried by the EV forms part of an additional fusion protein with an EV-protein separate to the EV-protein-ABD fusion protein; the therapeutic cargo protein may be fused into the fusion protein such that it is located on the inside of the EV, on the outside of the EV or located within the membrane of the EV (¶ [0091-0093]).
Therefore, claims 1-12 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Liang et al., (US 2023/0301926 A1; priority 07/03/2020) and is deemed to anticipate claims 1-12 as written and when given the broadest reasonable interpretation.
III. Claims 1-5 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Zhang et al., (PNAS, 2018, Vol. 115(29): E6927-E6936).
Zhang et al., (PNAS, 2018, Vol. 115(29): E6927-E6936) disclose protein compositions comprising an exosome, an arginase and tetraspanin (see Abstract; Fig. 3, page E6930; Fig. 4, page E6931; Fig. 7, page E6934; Discussion col. 2, page E6933- to col. 1, page E6934; and entire document).
Therefore, claims 1-5 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Zhang et al., (PNAS, 2018, Vol. 115(29): E6927-E6936) and is deemed to anticipate claims 1-5 as written and when given the broadest reasonable interpretation.
Since the Office does not have the facilities for examining and comparing applicants’ composition of the instant invention with composition of the prior art, the burden is on the applicant to show a novel or unobvious difference between the claimed composition of the instant invention and the composition of the prior art (i.e., that the composition of the prior art does not possess the same material structural and functional characteristics of the composition of the instant invention). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
Allowable Subject Matter/Conclusion
None of the claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GANAPATHIRAMA RAGHU whose telephone number is (571)272-4533. The examiner can normally be reached on M-F 8:30am-5pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert Mondesi can be reached on 408-918-7584. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/GANAPATHIRAMA RAGHU/ Primary Examiner, Art Unit 1652
