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
The instant application is a 35 U.S.C. 371 national phase application and claims priority to International Application No. PCT/IB2022/055858 (filing date 06/24/2022), which claims the benefit of the prior-filed Australian Provisional Patent Application Nos. AU2021903589, filing date 11/10/2021; and, AU2021901917, filing date 06/24/2021.
Status of Application/Claims
The preliminary amendment, filed 07/16/2024, is acknowledged. Claims 2-5, 11, 15-16, 18-19, 21, 23, 26-27, 29-31, 33, 35-36, and 40-46 are canceled. Claims 1, 6-8, 10, 12-14, 17, 20, 22, 24-25, 28, 32, 34, and 37-39 are currently amended. Claims 1, 6-10, 12-14, 17, 20, 22, 24-25, 28, 32, 34, and 37-39 are currently pending and are examined on the merits herein.
Information Disclosure Statements
The information disclosure statements (IDSs) submitted 06/13/2024 and 07/24/2024 list 2 non-patent literature references for which the pdf file is not properly uploaded. These references, respectively, are #3 Kim, et al. and #12 Totsuka, et al. The IDSs submitted on 06/13/2024, 07/16/2024, and 07/24/2024 have otherwise been fully considered by the examiner.
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).
The following amino acid sequences appear in the specification but to not list associated SEQ ID NOs:
KREAEAM, KREAEAEAM, REAEAEAEAM, REAEAEAM, REAEAM, EAEAEAEAM, EAEAEAM, EAEAM, EAEAEAEA, EAEAEA, EAEA.
Required response 1– 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- This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 - 1.825.
The following amino acid sequences appear in the specification and in claims 1 and 17, but to not appear in the sequence listing:
KREAEAM, KREAEAEAM, REAEAEAEAM, REAEAEAM, REAEAM, EAEAEAEAM, EAEAEAM, EAEAM, EAEAEAEA, EAEAEA, EAEA.
Required response 2– Applicant must provide:
A "Sequence Listing" part of the disclosure, as described above in item 1); as well as
An amendment specifically directing entry of the "Sequence Listing" part of the disclosure into the application in accordance with 1.825(b)(2);
A statement that the "Sequence Listing" includes no new matter in accordance with 1.825(b)(5); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(b)(4).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, 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;
If the "Sequence Listing" part of the disclosure is submitted according to item 1) b), c), or d) above, Applicant must also provide:
A replacement CRF in accordance with 1.825(b)(6); and
Statement according to item 2) a) or b) above.
Specific deficiency 3- This application fails to comply with the requirements of 37 CFR 1.821 - 1.825 because the "Sequence Listing" part of the disclosure submitted as a PDF file (37 CFR 1.821(c)(2)) or on physical sheets of paper (37 CFR 1.821(c)(3)) is not the same as the CRF of the "Sequence Listing" as required by 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii).
There are amino acid sequences for which the listed sequence in the sequence listing does not match the description provided in the specification. For example, Table 2 on p.59 indicates that SEQ ID NOs: 19, 20, and 21 are “B-Lac B variants” (i.e., variants of SEQ ID NO: 2). However, the amino acid sequences in the listing for SEQ ID NOs: 19-21 harbor amino acid residues D64 and V118, which are associated with the wild type “B-Lac A” form; whereas, amino acid residues G64 and A118 are associated with the “B-Lac B” form. Applicant is advised to check all sequences accordingly.
Required response 3- Applicant must provide:
A replacement "Sequence Listing" as described above in items 1) c) or d) in accordance with 37 CFR 1.825(b)(1)(ii) or (iii); as well as
An amendment specifically directing its entry into the application as required by 37 CFR 1.825(b)(2)(ii);
A statement that identified the locations of any deletions, replacements or additions to the “Sequence Listing” as required by 37 CFR 1.825(b)(3);
A statement that the "Sequence Listing" added by amendment includes no new matter as required by 37 CFR 1.825(b)(5);
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(b)(4); and
A statement that the content of the previously-filed CRF is identical to the "Sequence Listing" part of the disclosure added by amendment as required by 37 CFR 1.825(b)(7), where provided under item 1) c) or d) (note that where a "Sequence Listing" part of the disclosure is provided under item 1) a) or b), the text file will also serve as the CRF, and the statement of identity is not required);
OR
A CRF as required by 37 CFR 1.821(e)(1) or 1.821(e)(2); and
A statement that the content of the CRF is identical to the "Sequence Listing" part of the disclosure previously submitted as a PDF file (37 CFR 1.821(c)(2)) or on physical sheets of paper (37 CFR 1.821(c)(3)), as required by 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii).
Specification
The use of the terms Thermo Scientific, Pronalys, Labserv, New England Biolabs, and Thermo Fisher, which are trade names or marks used in commerce, have been noted in this application. The terms should be in all caps wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
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.
Claim Objections
Claims 1 and 17 are objected to because the following amino acid sequences appear in the claims but to not list associated SEQ ID NOs:
KREAEAM, KREAEAEAM, KREAEAEAEAM, REAEAEAEAM, REAEAEAM, REAEAM, EAEAEAEAM, EAEAEAM, EAEAM, EAEAEAEA, EAEAEA, EAEA.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(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.
Claims 17, 22, and 24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kim, et al. High-level expression of bovine β-lactoglobulin in Pichia pastoris and characterization of its physical properties. Protein Engineering 1997, 10:11, p.1339-1345 (herein referred to as Kim); as evidenced by NCBI_1BSO_A. Chain A, Protein-Bovine Beta-lactoglobulin A, Bos taurus, p.1-2 (published: 1998; herein referred to as NCBI_1BSO_A).
[AltContent: textbox (Instant SEQ ID NO: 1 vs NCBI_1BSO_A
[img-media_image1.png])]Kim teaches high-level expression of recombinant bovine β-lactoglobulin variant A (β-LG A) in Pichia pastoris (title; abstract; p.1340, col.1, para.1). As evidenced by NCBI_1BSO_A, wild type mature β-LG A is encoded by instant SEQ ID NO: 1 (see alignment below).
Kim teaches that the N-terminal sequence of the recombinant protein is Glu-Ala-Glu-Ala-Tyr-Val; and, that the β-LG has been expressed in the methylotropic yeast P. pastoris by fusion of the cDNA to the sequence coding for the α-mating factor (αMF) β-LG preproleader secretion signal peptide from S. cerevisiae which comprises the KREAEA site allowing for enzymatic processing (abstract; p.1339, col.2, para.4); and, that the leader sequence provides the benefit of effective secretion and directing the processing of recombinant β-LG (p.1344, col.2, para.2). Kim teaches that the enzymatic processing includes sequential removal of the Glu-Ala dipeptides that serve as spacer repeats, which are removed by STE13 dipeptidyl aminopeptidase following KEX2 mediated cleavage between Arg85/R85 and Glu86/E (p.1341, col.2, para.2). Thus, Kim teaches a recombinant, elongated β-LG A protein having an amino acid sequence comprising the core wild-type mature β-LG A wherein only the first two amino acids of the mature β-LG A sequence differ from that taught by NCBI (i.e., Kim teaches a core sequence having at least 70% identity and greater than 95% identity); and, an elongation sequence consisting of KREAEA, EA or EAEA, which all exist at various enzymatic processing steps.
Claims 1, 7-10, 12, 17, 22, and 24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Uhrinova, et al. Complete assignment of 1H, 13C and 15N chemical shifts for bovine β-lactoglobulin: Secondary structure and topology of the native state is retained in a partially unfolded form. J. of Biomol. NMR 1998, 12, p.89-107 (herein referred to as Uhrinova); as evidenced by NCBI_1BSO_A.
Uhrinova teaches recombinant expression of bovine β-LG A in P. pastoris (p.90-91). As evidenced by NCBI_1BSO_A, this β-LG A isoform is encoded by instant SEQ ID NO: 1 (see alignment above). Uhrinova teaches that β-lactoglobulin (β-LG) has been the subject of extensive physicochemical studies over the last 60 years due to it being readily available and due to its commercial importance in milk processing (p.90, col.1, para.3). Uhrinova teaches that there are two common variants of bovine β-LG which differ ty two amino acid residues that have different aggregation properties during milk processing (abstract): position 64 is an aspartate/D in variant A and is a glycine/G in variant B; and, position 118 is a valine/V in variant A and is an alanine/A in variant B (p.90, col.1, para.2). Additionally, Uhrinova teaches a crystal structure derived from a recombinant A/B mixture (p.90, col.1, para.2 and col.2, para.3).
Uhrinova teaches that the N-terminal sequence of the construct used is Glu-Ala-Tyr-Val-Thr-Met-Lys, wherein the beginning “Leu-Ile” residues are substituted for “Ala-Tyr”; that N-terminal analysis and mass spectrometry revealed that the N-terminus is ragged which is a common problem with the expression vector; and, that there was batch-to-batch variation in the relative quantities of N-terminal sequences present including Glu-Ala-Tyr-Val-Thr-Gln, Ala-Tyr-Val-Thr-Gln, and Tyr-Val-Thr-Gln and Val-Thr-Gln.
Uhrinova also teaches that for their double-labelled sample, N-terminal analysis and assignment of NMR spectra confirmed that the full-length, uncleaved sequence was the major component at >80% (p.91, col.1, para.1). Thus, Uhrinova teaches a protein that is elongated compared to the wild type core β-LG sequence, has at least 70% identity to the WT sequence, has at least 95% identity to the WT sequence, and wherein the protein also comprises an N-terminal “EA” sequence; and, teaches compositions comprising this construct and other β-LG constructs wherein the proteins differ in amino acid sequence; wherein there are 2 substitutions relative to wild type mature β-LG (i.e., instant SEQ ID NO: 1).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 7-10, 12, 17, 22, and 24-25 are rejected under 35 U.S.C. 103 as being unpatentable over Keppler, et al. Towards recombinantly produced milk proteins: Physicochemical and emulsifying properties of engineered whey protein beta-lactoglobulin variants. Food Hydrocolloids 2021, 110: 106132, p.1-14 (herein referred to as Keppler); and, further in view of Kim.
Keppler teaches that the production of animal proteins as sole protein source is not sustainable because it takes up enormous environmental impact with low production efficiently (p.1). Keppler teaches that alternative and sustainable sources such as plants, insects, fungi, and bacteria are being tested for their natural amino acid value and protein yield (p.1). Keppler teaches the potential interest of recombinantly produced dairy proteins; and, that the production of whey protein β-LG is particularly interesting as it is the main protein in bovine whey and an important component in many foods; and, that β-LG has versatile functional properties as a gelling, foaming, and emulsifying agent (p.2, col.1, para.3). (p.2, col.2). Keppler teaches that β-LG exists predominantly in two isoforms, β-LG A and β-LG B, in bovine milk, which differ by two amino acids. Keppler teaches recombinant expression in E. coli of two bovine β-LG variant B constructs, wherein the first construct has an N-terminal methionine and the second construct has the N-terminal methionine as well as L1A and I2S mutations for the benefit of ensuring correct cleavage of the N-terminal methionine (p.2, col.2, para.4). Thus, Keppler teaches a composition comprising two recombinant β-LG proteins of differing amino acid sequences with at least 70% identity to WT β-LG/at least 95% identity to wild type β-LG, and comprises at least 60% of the total β-LG protein. As β-LG B is encoded by instant SEQ ID NO: 2, Keppler teaches a composition wherein the substituted β-LG consists of 2 amino acid substitutions compared to instant SEQ ID NO: 2 and 4 amino acid substitutions compared to SEQ ID NO: 1.
Keppler does not teach the elongated N-terminal amino acid sequences recited in instant claims 1 and 17; or, explicitly teach a food product (instant claim 25).
While Keppler does not explicitly teach a particular food product, Keppler also teaches the importance of the study as it relates to production of food products for the benefits of providing for more production of non-animal derived protein sources to improve sustainability and lower environmental impacts.
Kim teaches the use of preproα-MF leader sequences derived from S. cerevisiae, as described above, for the benefits of enhancing effective secretion and directing the processing of the recombinant β-LG (p.1344, col.2, para.2), which are processed by STE13 and KEX2 to produce constructs with the EAEA and EA leader/elongation sequences.
It would have been obvious for one of ordinary skill in the art before the effective filing date to further combine the additional teachings of Keppler and to combine the teachings of Keppler with the teachings of Kim by modifying the composition comprising β-LG constructs (taught by Keppler) to harbor an N-terminal preproα-MF leader sequence (taught by Kim), which is processed by STE13 and KEX2 to produce constructs with EAEA and EA leader sequences, in order to receive the expected benefit of enhancing secretion and processing of the β-LG constructs (taught by Kim) for the benefit of producing food products that ensure food protein sustainability and have a reduced environmental impact than animal-only food sources (taught by Keppler).
Claims 1, 6-7, 17, 20, 22, 24-25, 28, 32, and 37-39 are rejected under 35 U.S.C. 103 as being unpatentable over Pandya, et al.—US9924728B2. Food compositions comprising one or both of recombinant beta-lactoglobulin protein and recombinant alpha-lactalbumin protein (publication date; 06/15/2017; effective filing date: 08/21/2014; herein referred to as Pandya), as evidenced by NCBI_1BSO_A and as evidenced by UniProt: P02754-LACB_BOVIN, p.1-9 (published: 08-01-1991; herein referred to as UP_P02754); as further evidenced by Whole Foods Market. Our guide to starting a vegan diet. 04-13-2021. Internet – Wayback Machine, p.7 (herein referred to as WFM); and, further in view of Kim.
Pandya teaches methods and compositions that comprise recombinant whey protein (i.e., β-LG protein variants and α-lactalbumin protein), as well as casein protein (title; abstract; Fig.9A). Pandya’s invention is directed toward dairy substitutes, methods of manufacturing, and compositions comprising animal-free milk fats and proteins for food applications including milk products (i.e., food products; col.71, para.8), such as milk (i.e., a dairy beverage, beverage), butter (i.e., a bar or solid moulded form), cheese, infant formula (col.51, para.4), yogurt, and cream (col.1, para.2). Thus, as evidenced by WFM, Panda teaches food products suitable for a vegan diet as the compositions do not contain animal products (p.2, para.3). Pandya teaches that although mammal-produced milk, such as bovine milk, is considered to be an ideal source of nutrition, various milk alternatives, such as plant- or nut-based milks have been pursued for reasons related to mammal- or mammalian-produced milk’s allergenicity, lactose intolerance of certain components, personal preference, and the perceived environmental benefits of reduced dairy industry (col.1, para.3). Pandya teaches, however, that existing dairy milk alternatives, such as soy, almond, or coconut milk fall short both in flavor and functionality (col.2 para.1). Pandya teaches compositions wherein the compositions can comprise any of the following components: one or both recombinant β-LG, and additional protein sources including α-lactalbumin, α-S1-casein, α-S2-casein, lactoferrin, transferrin, and serum albumin (title; abstract; col.8, para.1; col.64, para.2). As evidenced by NCBI_1BSO_A, wild type mature β-LG A is encoded by instant SEQ ID NO: 1 (see alignment above); and as evidenced by UP_P02754, wild type mature β-LG B is encoded by instant SEQ ID NO: 2 (see [AltContent: textbox (Instant SEQ ID NO: 2 vs Uniprot_P02754
[img-media_image2.png])]alignment below).
While Pandya teaches use of the “SP_MfαT” signal peptide, Pandya does not discuss or provide a motivation for using this N-terminal sequences derived from this signal peptide (instant claim 1, 6-7, 17, 20, 22, and 24-25).
Kim teaches the use of preproα-MF leader sequences derived from S. cerevisiae, as described above, for the benefits of enhancing effective secretion and directing the processing of the recombinant β-LG (p.1344, col.2, para.2), which are processed by STE13 and KEX2 to produce constructs with the EAEA and EA leader/elongation sequences.
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date to combine the collective teachings of Pandya with the teachings of Kim by modifying a composition comprising β-LG constructs (taught by Pandya) to harbor an N-terminal preproα-MF leader sequence (taught by Kim), which is processed by STE13 and KEX2 to produce constructs with EAEA and EA leader sequences, in order to receive the expected benefit of enhancing secretion and processing of the β-LG constructs (taught by Kim) for the benefit of producing food products that ensure food protein sustainability and have a reduced environmental impact than animal-only food sources (taught by Pandya). It would have further been obvious to produce a composition comprising differing recombinant β-LG variant proteins that have differing amino acid sequences and which each harbor an α-MF leader sequence because the combination of teachings by Pandya teaches various compositions comprising one or both β-LG proteins; and, a composition comprising both the β-LG A and β-LG B variants (i.e., instant wild types SEQ ID NOs: 1 and 2, respectively) each with either the EAEA or EA elongation sequence derived from the signal peptide, taught by Kim, would predictably result in compositions comprising instant SEQ ID NO: 71 or 72, respectively for β-LG A; and, instant SEQ ID NO: 73 or 74 for β-LG B. It would have further been obvious that some of Pandya’s compositions do not include any other recombinant non-β-lactoglobulin proteins other than the recombinant β-LG proteins because the combination of Pandya’s teachings teaches that compositions may include other protein sources, but other protein sources are not required (instant claim 38).
Claims 1, 10, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Uhrinova, as applied to claims 1 and 10 above; further in view of Pandya; and, further in view of UniProt.Q9XFX4 – CardB_CYNCA. 2006 (herein referred to as UP-protease); and, further in view of Barros and Malcata. Molecular characterization of peptides released from β-lactoglobulin and α-lactalbumin via cardosins A and B. J. Dairy Sci 2006, 89, p.483-494 (herein referred to as Barros).
Uhrinova teaches a composition comprising recombinant β-LG proteins that differ in amino acid sequence and that comprise amino acid substitutions, as described above for instant claims 1 and 10.
Uhrinova does not teach that the composition is substantially free of aspartyl protease-like activity (instant claim 14).
Pandya teaches various recombinant milk protein food products wherein the compositions can comprise varied amounts and combinations of different milk and whey proteins, including one or both recombinant β-LG, and optionally additional protein sources including α-lactalbumin, α-S1-casein, α-S2-casein, lactoferrin, transferrin, and serum albumin (title; abstract; col.8, para.1; col.64, para.2).
UP-protease teaches an aspartic protease CardB, which cleaves α-lactalbumin but not β-lactoglobulin.
Barros teaches cardosin A and cardosin B aspartyl protease activity on different whey protein substrates. Barros teaches that cardosins A and B are not active on β-LG (abstract; conclusion).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Uhrinova with the teachings of Pandya and UP-protease and Barros by modifying the composition (taught by Uhrinova) to comprise predominantly β-lactoglobulin rather than α-lactalbumin (taught by Pandya) in order to receive the benefit of reduced protease activity (taught by UP-protease and Barros). One would have a reasonable expectation of success because Pandya teaches that the composition components can be varied and can comprise different β-LG proteins wherein additional proteins are optional; and, UP-protease and Barros teach that aspartyl protease activity is reduced when only β-LG is the available protein as β-LG is not a substrate for cardosin A or B.
Claims 32, and 34 are rejected under 35 U.S.C. 103 as being unpatentable over Pandya, as applied to claims 17, 25, and 32 above; and, further in view of Alves, et al. Mixing animal and plant proteins: Is this a way to improve protein techno-functionalities? Food Hydrocolloids 2019, 97: 105171, p.1-10 (herein referred to as Alves).
The combination of Pandya’s teachings teaches a composition comprising two or more recombinant β-LG proteins of differing amino acid sequences for the purpose of producing a food product, as described above for instant claims 17 and 25. Pandya also teaches compositions for food products that comprise additional sources of protein, as described in claim 32 above.
Pandya does not teach that the additional source of protein is non-dairy protein (instant claim 32); or, that the non-dairy protein is derived from plant, algae, fungi, or combination thereof (instant claim 34).
Alves teaches an overview of studies about animal and plant protein interactions; and, teaches that mixing of animal and plant proteins can be efficient in modulating texture of protein gels, and has the ability to form low-cost edible films and produce stable emulsions and foams (title; abstract). Alves further teaches that while the use of plant proteins as ingredients is associated with some limitations, plant proteins display advantages including lower cost of production, low allergenicity, and unique techno-functional properties (p.1, col.1, para.1). Alves summarizes several studies comprising combinations of whey/β-LG protein and plant proteins, including pea and soy proteins (Table 2).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to further combine the teachings of Pandya with the teachings of Alves by modifying the composition of Pandya comprising β-LG proteins to also include additional protein sources (also taught by Pandya) wherein the additional protein is from plant proteins such as soy or pea protein (taught by Alves and recited Table 2 refs) in order to receive the benefit that food products comprising plant protein provide for lower cost and allergenicity than animal protein. One of ordinary skill would have a reasonable expectation of success because Alves teaches studies comprising both β-LG/whey protein and plant protein.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Co-pending Application 18/707,670
Claims 1, 6-10, 12, 14, 17, 20, 22, 24-25, 28, 32, 34, and 37-39 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6, 8-10, and 12 of copending Application No. 18/707,670 (herein referred to as App’670); further in view of Pandya; further in view of Kim; further in view of Keppler; and, further in view of Alves.
App’670 teaches a food product comprising a composition comprising one or more milk recombinant polypeptides that is/are β-LG, wherein the composition is substantially free of aspartyl protease-like activity (App’670 claims 1 and 8, and 3-4; instant claims 1, 17, 14, 22, and 24-25); wherein the composition comprises casein (App’670 claims 2 and 8; instant claim 39); wherein the food product further comprises a non-dairy source of protein (App’670 claim 5; instant claim 32); wherein the product is a fermented food, yogurt, soup, sauce, bar, gel, nutritional formulation, beverage, beverage whitener, cheese, dairy tofu, or dessert (App’670 claim 6; instant claim 28); and wherein the polypeptides are encodes by polynucleotides that harbor “leader” sequences (App’670 claim 12; instant claims 1 and 17).
App’670 does not explicitly teach that the “leader” sequences are elongation sequences as recited in instant claims 1 and 17; that there are two or more β-LGs (instant claims 7); that the elongated β-LGs encoded by the SEQ ID NOs of instant claims 6 and 20; that the composition comprises elongated β-LG that is at least about 4% of total recombinant β-LG (instant claim 8); that the elongated β-LG is at least about 40% (instant claim 9); that the β-LG comprises 1-10 substitutions relative to WT β-LG (instant claims 10 and 12); that the food product comprises non-dairy protein from a plant source (instant claim 34); or, that the food product is suitable for a vegan diet (instant claim 37).
Pandya teaches methods and compositions that comprise recombinant whey protein (i.e., β-LG protein variants and α-lactalbumin protein), as well as casein protein (title; abstract; Fig.9A). Pandya’s invention is directed toward dairy substitutes, methods of manufacturing, and compositions comprising animal-free milk fats and proteins for food applications including milk products (i.e., food products; col.71, para.8), such as milk (i.e., a dairy beverage, beverage), butter (i.e., a bar or solid moulded form), cheese, infant formula (col.51, para.4), yogurt, and cream (col.1, para.2). Thus, as evidenced by WFM, Panda teaches food products suitable for a vegan diet as the compositions do not contain animal products (p.2, para.3). Pandya teaches that although mammal-produced milk, such as bovine milk, is considered to be an ideal source of nutrition, various milk alternatives, such as plant- or nut-based milks have been pursued for reasons related to mammal- or mammalian-produced milk’s allergenicity, lactose intolerance of certain components, personal preference, and the perceived environmental benefits of reduced dairy industry (col.1, para.3). Pandya teaches, however, that existing dairy milk alternatives, such as soy, almond, or coconut milk fall short both in flavor and functionality (col.2 para.1). Pandya teaches compositions wherein the compositions can comprise any of the following components: one or both recombinant β-LG, and additional protein sources including α-lactalbumin, α-S1-casein, α-S2-casein, lactoferrin, transferrin, and serum albumin (title; abstract; col.8, para.1; col.64, para.2). As evidenced by NCBI_1BSO_A, wild type mature β-LG A is encoded by instant SEQ ID NO: 1 (see alignment above); and as evidenced by UP_P02754, wild type mature β-LG B is encoded by instant SEQ ID NO: 2 (see [AltContent: textbox (Instant SEQ ID NO: 2 vs Uniprot_P02754
[img-media_image2.png])]alignment below).
Kim teaches the use of preproα-MF leader sequences derived from S. cerevisiae, as described above, for the benefits of enhancing effective secretion and directing the processing of the recombinant β-LG (p.1344, col.2, para.2), which are processed by STE13 and KEX2 to produce constructs with the EAEA and EA leader/elongation sequences.
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date to combine the teachings of App’670 with the teachings of Pandya and Kim by modifying a food product (taught by App’670) to comprise a composition comprising β-LG constructs (taught by App’670 and Pandya) to harbor an N-terminal preproα-MF leader sequence (taught by Kim), which is processed by STE13 and KEX2 to produce constructs with EAEA and EA leader sequences, in order to receive the expected benefit of enhancing secretion and processing of the β-LG constructs (taught by Kim) for the benefit of producing food products that ensure food protein sustainability and have a reduced environmental impact than animal-only food sources (taught by Pandya). It would have further been obvious to produce a food product (taught by App’670) comprising a composition comprising differing recombinant β-LG (taught by App’670) variant proteins that have differing amino acid sequences (Pandya) and which each harbor an α-MF leader sequence (taught by Kim) because the combination of teachings by Pandya teaches various compositions comprising one or both β-LG proteins; and, a composition comprising both the β-LG A and β-LG B variants (i.e., instant wild types SEQ ID NOs: 1 and 2, respectively) each with either the EAEA or EA elongation sequence derived from the signal peptide, taught by Kim, would predictably result in compositions comprising instant SEQ ID NO: 71 or 72, respectively for β-LG A; and, instant SEQ ID NO: 73 or 74 for β-LG B. It would have further been obvious that some of Pandya’s compositions do not include any other recombinant non-β-lactoglobulin proteins because the combination of Pandya’s teachings teaches that compositions may include other protein sources for food products.
Keppler teaches that the production of animal proteins as sole protein source is not sustainable because it takes up enormous environmental impact with low production efficiently (p.1). Keppler teaches that alternative and sustainable sources such as plants, insects, fungi, and bacteria are being tested for their natural amino acid value and protein yield (p.1). Keppler teaches the potential interest of recombinantly produced dairy proteins; and, that the production of whey protein β-LG is particularly interesting as it is the main protein in bovine whey and an important component in many foods; and, that β-LG has versatile functional properties as a gelling, foaming, and emulsifying agent (p.2, col.1, para.3). (p.2, col.2). Keppler teaches that β-LG exists predominantly in two isoforms, β-LG A and β-LG B, in bovine milk, which differ by two amino acids. Keppler teaches recombinant expression in E. coli of two bovine β-LG variant B constructs, wherein the first construct has an N-terminal methionine and the second construct has the N-terminal methionine as well as L1A and I2S mutations for the benefit of ensuring correct cleavage of the N-terminal methionine (p.2, col.2, para.4). Thus, Keppler teaches a composition comprising two recombinant β-LG proteins of differing amino acid sequences with at least 70% identity to WT β-LG/at least 95% identity to wild type β-LG, and comprises at least 60% of the total β-LG protein. As β-LG B is encoded by instant SEQ ID NO: 2, Keppler teaches a composition wherein the substituted β-LG consists of 2 amino acid substitutions compared to instant SEQ ID NO: 2 and 4 amino acid substitutions compared to SEQ ID NO: 1.
Keppler does not teach the elongated N-terminal amino acid sequences recited in instant claims 1 and 17; or, explicitly teach a food product (instant claim 25).
While Keppler does not explicitly teach a particular food product, Keppler also teaches the importance of the study as it relates to production of food products for the benefits of providing for more production of non-animal derived protein sources to improve sustainability and lower environmental impacts.
It would have been obvious for one of ordinary skill in the art before the effective filing date to further combine the teachings of App’670, Pandya, and Kim with the teachings of Keppler by modifying the composition comprising β-LG constructs harboring L1A and I2S mutations for the benefit of ensuring correct cleavage of the N-terminal methionine (taught by Keppler) to also harbor an N-terminal preproα-MF leader sequence (taught by Kim), which is processed by STE13 and KEX2 to produce constructs with EAEA and EA leader sequences, in order to receive the expected benefit of enhancing secretion and processing of the β-LG constructs (taught by Kim) for the benefit of producing food products that ensure food protein sustainability and have a reduced environmental impact than animal-only food sources (taught by Keppler).
Alves teaches an overview of studies about animal and plant protein interactions; and, teaches that mixing of animal and plant proteins can be efficient in modulating texture of protein gels, and has the ability to form low-cost edible films and produce stable emulsions and foams (title; abstract). Alves further teaches that while the use of plant proteins as ingredients is associated with some limitations, plant proteins display advantages including lower cost of production, low allergenicity, and unique techno-functional properties (p.1, col.1, para.1). Alves summarizes several studies comprising combinations of whey/β-LG protein and plant proteins, including pea and soy proteins (Table 2).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to further combine the teachings of App’670, Pandya, Kim, and Keppler with the teachings of Alves by modifying the food product (taught by App’670) comprising the composition of Pandya comprising β-LG proteins harboring substitutions (taught by Keppler) and the αMF leader sequence (taught by Kim) to also include additional protein sources (also taught by Pandya) wherein the additional protein is from plant proteins such as soy or pea protein (taught by Alves and recited Table 2 refs) in order to receive the benefit that food products comprising plant protein provide for lower cost and allergenicity than animal protein. One of ordinary skill would have a reasonable expectation of success because Alves teaches studies comprising both β-LG/whey protein and plant protein.
This is a provisional nonstatutory double patenting rejection.
Conclusion
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/JAMI MICHELLE GURLEY/Examiner, Art Unit 1647
/JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647
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