DETAILED ACTION
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
The amendment filed on 12-18-2025 is acknowledged. Claims 9 and 18 have been amended. Claims 1-8 have been canceled. Claims 20-26 have been added. Claims 9-26 are pending.
Election/Restrictions
Applicant's election with traverse of Group II in the response filed 12/18/2025 is acknowledged. The traversal is on the ground(s) that examination of all claims would not be an undue burden. This is not found persuasive because burden is not a criterion in determining whether a restriction is proper when said restriction is made under PCT Rules 13.1 and 13.2.
The requirement is still deemed proper and is therefore made FINAL.
Consequently, claims 15-16, 22 and 26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 9-14, 17-21 and 23-25 are currently under examination.
Information Disclosure Statement
The Information Disclosure Statement filed on 12-9-2022 has been considered. An initialed copy is attached hereto.
It should be noted that the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
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 - Sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.831(c). Sequence identifiers for sequences (i.e., “SEQ ID NO:X” or the like) must appear either in the drawings or in the Brief Description of the Drawings. While it is noted that the specification refers to “SEQ ID NO:8-11” in reference to Figure 1 and “SEQ ID NO:8-13” in reference to Figure 9, there is no delineation regarding which SEQ ID NO: is associated with a given sequence.
Required response – Applicant must provide:
Amended drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers (i.e., “SEQ ID NO:X” or the like) into the Brief Description of the Drawings, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Claim Objections
Claim 11 is objected to for utilizing the acronym “Pip” without defining it upon its first recitation.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 10-14 and 18 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural product without significantly more.
Laws of nature or natural phenomena include naturally occurring principles/ relations that are naturally occurring or that do not have markedly different characteristics compared to what occurs in nature (MPEP2106.04(b)).
“The law of nature and natural phenomenon exceptions reflect the Supreme Court's view that the basic tools of scientific and technological work are not patentable, because the "manifestations of laws of nature" are "part of the storehouse of knowledge," "free to all men and reserved exclusively to none." Funk Bros. Seed Co. v. Kalo Inoculant Co., 333 U.S. 127, 130, 76 USPQ 280, 281 (1948). Thus, "a new mineral discovered in the earth or a new plant found in the wild is not patentable subject matter" under Section 101. Diamond v. Chakrabarty, 447 U.S. 303, 309, 206 USPQ 193, 197 (1980). "Likewise, Einstein could not patent his celebrated law that E=mc2; nor could Newton have patented the law of gravity." Id. Nor can one patent "a novel and useful mathematical formula," Parker v. Flook, 437 U.S. 584, 585, 198 USPQ 193, 195 (1978); electromagnetism or steam power, O’Reilly v. Morse, 56 U.S. (15 How.) 62, 113-114 (1853); or "[t]he qualities of ... bacteria, ... the heat of the sun, electricity, or the qualities of metals," Funk, 333 U.S. at 130, 76 USPQ at 281; see also Le Roy v. Tatham, 55 U.S. (14 How.) 156, 175 (1853).”
Products of nature are analyzed under 35 USC 101 through the “markedly different characteristics analysis”. MPEP 2106.04(c) as a part of step 2A prong one of the analysis.
“If the claim includes a nature-based product that has markedly different characteristics, then the claim does not recite a product of nature exception and is eligible (Step 2A: NO) at Pathway B unless the claim recites another exception (such as a law of nature or abstract idea, or a different natural phenomenon). For claims where the entire claim is a single nature-based product (e.g., a claim to "a Lactobacillus lactis strain with inactivated nisin production), once a markedly different characteristic in that product is shown, no further analysis would be necessary for eligibility because no product of nature exception is recited (i.e., Step 2B is not necessary because the answer to Step 2A is NO). For claims including limitations in addition to the nature-based product, further eligibility analysis is required.
If the claim includes a nature-based product that does not exhibit markedly different characteristics from its naturally occurring counterpart in its natural state, then the claim recites a "product of nature" exception, and requires further analysis in Step 2A Prong Two to determine whether the claim as a whole integrates the exception into a practical application.
Claims 10-13 and 17-18 recite the following natural product:
A nisin-producing Lactococcus lactis strain comprising an inactivated phage infection protein TC#3.A.1.155.1, wherein the strain is selected from Lactococcus lactis subsp. lactis, Lactococcus lactis subsp. cremoris, and Lactococcus lactis subsp. lactis biovar diacetylactis
MPEP2106.04(C) II sets forth:
Appropriate characteristics can be expressed as the nature-based product’s structure, function, and/or other properties, and are evaluated on a case-by-case basis. Non-limiting examples of the types of characteristics considered by the courts when determining whether there is a marked difference include:
• Biological or pharmacological functions or activities;
• Chemical and physical properties;
• Phenotype, including functional and structural characteristics; and
• Structure and form, whether chemical, genetic or physical.
“To show a marked difference, a characteristic must be changed as compared to nature, and cannot be an inherent or innate characteristic of the naturally occurring counterpart or an incidental change in a characteristic of the naturally occurring counterpart. Myriad, 569 U.S. at 580, 106 USPQ2d at 1974-75. Thus, in order to be markedly different, applicant must have caused the claimed product to possess at least one characteristic that is different from that of the counterpart.” (MPEP2106.04 (c)II. C).
Comparing the relevant characteristics between the product of claims 10-13 and 17-18 and its naturally occurring counterpart, the examiner finds no markedly difference characteristics between the characteristics. As set forth in the specification mutations in the phage infection protein of Lactococcus lactis are naturally inactivated (see Example 1). Moreover, Garbutt et al. (Journal of Dairy Science Vol. 80, pages 1512-1519 – IDS filed on 12-9-2022) clearly disclose that the Lactococcus lactis ssp. lactis strains C2 and ML3 have spontaneously pip mutants that are phage-resistant (see page 1512). While Garbutt et al. do not explicitly disclose that said mutation results in increased nisin production, the disclosed “mutant” would necessarily have said ability.
If there are no markedly different characteristics between the product of the claim and the naturally occurring counterpart, the claim is probed for the presence of additional limitations. The claimed additional elements are analyzed alone or in combination to determine if the natural product is sufficiently different than is integrated into a practical application (MPEP 2106.04(d).I.; MPEP 2106.05(a-h)). If the claim contains no additional elements beyond the natural product, the claim fails to integrate the natural product into a practical application (MPEP 2106.04(d).III).
There are no additional limitations to the natural product in claim 10-13 and 17-18.
The recitation of the specific residues of the inactivated phage infection protein is not considered an additional limitation as it merely describes naturally occurring mutations.
Considering the additional limitations in addition to the natural product together as a whole, the additional elements do not rise to the level of significantly more than the natural product.
In combination, the lack of additional limitations, acted upon by the judicial exception (or natural law, or natural product), fail to rise to the level of significantly more. No additional limitation has clearly been identified.
The claims have all been examined to identify the presence of a naturally occurring product or natural phenomena. Each additional limitation in the claims has been addressed, alone and in combination, to determine whether the additional limitations integrate the judicial exception into a practical application. Each additional limitation in the claims has been addressed, alone and in combination, to determine whether those additional limitations provide an inventive concept which provides significantly more than those exceptions. Individually, the limitations of the claims and the claims as a whole have been found lacking.
For these reasons, the claims, when the limitations are considered individually and as a whole, are rejected under 35 USC § 101 as being directed to non-statutory subject matter.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Biological Deposit
Claims 13 and 19 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
It is apparent that the Lactococcus lactis strains represented by the DSMZ accession numbers DSM 3302 and DSM 18874 are required in order to practice the invention. The deposit of biological organisms is considered by the Examiner to be necessary for the enablement of the current invention (see 37 CRF 1.808(a)). The examiner acknowledges the deposit of organisms under the DSMZ accession numbers DSM 3302 and DSM 18874 in partial compliance with this requirement. However, said deposits are not in full compliance with 37 CFR 1.803-1.809.
If the deposit is made under terms of the Budapest Treaty, then an affidavit or declaration by Applicants or person(s) associated with the patent owner (assignee) who is in a position to make such assurances, or a statement by an attorney of record over his or her signature, stating that the deposit has been made under the terms of the Budapest Treaty and that all restrictions imposed by the depositor on the availability to the public of the deposited material will be irrevocably removed upon the granting of a patent, would satisfy the deposit requirements. See 37 CFR 1.808.
If a deposit is not made under the terms of the Budapest Treaty, then an affidavit, or declaration by Applicants or person(s) associated with the patent owner (assignee) who is in a position to make such assurances, or a statement by an attorney of record over his or her signature, stating that the following criteria have been met:
1) during the pendency of the application, access to the deposit will be afforded to one determined by the Commissioner to be entitled thereto;
2) all restrictions imposed by the depositor on the availability to the public of the deposited material will be irrevocably removed upon the granting of a patent; and
3) the deposits will be maintained for a term of at least thirty (30) years from the date of the deposit or for the enforceable life of the patent or for a period of at least five (5) years after the most recent request for the furnishing of a sample of the deposited material, whichever is longest; and
4) a viability statement in accordance with the provisions of 37 CFR 1.807; and
5) the deposit will be replaced should it become necessary due to inviability, contamination or loss of capability to function in the manner described in the specification.
In addition, the identifying information set forth in 37 CRF 1.809(d) may need to be added to the specification. See 37 CFR 1.803 – 1.809 for additional explanation of these requirements.
Written Description
Claims 9-14, 17-21 and 23-25 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The instant claims are drawn to nisin producing Lactococcus lactis stains with an inactive phage infection protein TC#3A.1.155.1. The rejected claims further require:
said Lactococcus lactis strain has increased nisin production;
said strain is selected from Lactococcus lactis subsp. lactis, Lactococcus lactis subsp. cremoris, and Lactococcus lactis subsp. lactis biovar diacetylactis (claims 10 and 23);
the inactivated phage infection protein fully or substantially lacks one, two, three, four, five or six predicted Pip transmembrane domains corresponding to amino acids 14-38, 694-714, 738- 760, 768-790, 796-819 and 849-873 of SEQ ID NO: 1, respectively, or the inactivated phage infection protein fully or substantially lacks one, two, three, four or five predicted Pip transmembrane domains corresponding to amino acids 694-714, 738-760, 768- 790, 796-819 or 849-873 of SEQ ID NO: 1 (claim 11);
The nisin-producing Lactococcus lactis strain is obtained by a process comprising phage-hardening against a bacteriophage which recognizes the phage infection protein (TC#3.A.1.155.1) (claims 12 and 21);
The phage infection protein having a polypeptide sequence with at least 90% homology to SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10 or SEQ ID NO: 11 (claim 18);
the mutating of the mother strain gene(s) step comprises phage-hardening against a c2 type bacteriophage (claim 19);
the mutating of mutating mother strain genes comprises fully or partially deleting gene(s) which encode the phage infection protein or regulate expression of gene(s) which encode the phage infection protein (claim 20); and
the nisin-producing Lactococcus lactis mother strain produces one or both of nisin A and nisin Z (claim 22).
Consequently, the rejected claims encompass a myriad of differing Lactococcus lactis strains containing a multitude of mutations.
To adequately describe the genus of Lactococcus lactis strains the claimed genotypic and phenotypic characteristics, Applicant must not only describe the Lactococcus lactis strains produce nisin and a given phage infection protein but also describe the “genes which encode the phage infection protein or regulate expression of genes which encode the phage infection protein” and the means by which said modification is achieved. However, the specification does not disclose distinguishing and identifying features of a representative number of members of the genus of Lactococcus lactis strains to which the claims are drawn, such as a correlation between the structure of the Lactococcus lactis strains (i.e. genome and phenotype) and its recited function (i.e. inactivated phage infection protein and/or having increased nisin production) so that the skilled artisan could immediately envision, or recognize at least a substantial number of members of the claimed genus of mutated Lactococcus lactis strains. The specification is limited to obtaining Lactococcus lactis strains A-D via culturing the Lactococcus lactis DMS 18874 strain (see Example 1) and the subsequent phenotypic characterization of said strains. Said disclosure cannot be extrapolated to the full scope of the recombinant microbial species encompassed by the rejected claims. Therefore, since the specification fails to adequately describe at least a substantial number of members of the genus of recombinant microbial strains to which the claims refer and hence fails to meet the written description requirements as set forth int 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph.
MPEP § 2163.02 states, “[a]n objective standard for determining compliance with the written description requirement is, 'does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed' ”. The courts have decided:
The purpose of the “written description” requirement is broader than to merely explain how to “make and use”; the applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the “written description” inquiry, whatever is now claimed.
See Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Federal Circuit, 1991). Furthermore, the written description provision of 35 USC § 112 is severable from its enablement provision; and adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
MPEP 2163.02 further states, “[p]ossession may be shown in a variety of ways including description of an actual reduction to practice, or by showing the invention was 'ready for patenting' such as by disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention” See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); Regents of the Univ. of Cal. v. Eli Lilly, 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997); Amgen, Inc. v. Chugai Pharm., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it"). Moreover, because the claims encompass a genus of variant species, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. However, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; nor has Applicant shown the invention was “ready for patenting” by disclosure of drawings or structural chemical formulas that show that the invention was complete; nor has Applicant described distinguishing identifying characteristics sufficient to show that Applicant were in possession of the claimed invention at the time the application was filed.
Additionally, MPEP 2163 states:
"A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed." In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004)”
And:
For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are "representative of the full variety or scope of the genus," or by the establishment of "a reasonable structure-function correlation." Such correlations may be established "by the inventor as described in the specification," or they may be "known in the art at the time of the filing date." See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014) (Holding that claims to all human antibodies that bind IL-12 with a particular binding affinity rate constant (i.e., koff) were not adequately supported by a specification describing only a single type of human antibody having the claimed features because the disclosed antibody was not representative of other types of antibodies in the claimed genus, as demonstrated by the fact that other disclosed antibodies had different types of heavy and light chains, and shared only a 50% sequence similarity in their variable regions with the disclosed antibodies.).
Moreover, the describing of a biological entity by their functions was addressed in the Centocor decision (CENTOCOR ORTHO BIOTECH, INC. v ABBOTT LABORATORIES (Fed Cir, 2010-1144, 2/23/2011)). In said case the court stated”
To satisfy the written description requirement, "the applicant must 'convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention,' and demonstrate that by disclosure in the specification of the patent." Carnegie Mellon Univ. v. Hoffmann-La Roche Inc., 541 F.3d 1115, 1122 (Fed. Cir. 2008) (quoting Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563-64 (Fed. Cir. 1991)). Assessing such "possession as shown in the disclosure" requires "an objective inquiry into the four corners of the specification." Ariad, 598 F.3d at 1351. Ultimately, "the specification must describe an invention understandable to [a person of ordinary skill in the art] and show that the inventor actually invented the invention claimed." Id. A "mere wish or plan" for obtaining the claimed invention is not adequate written description. Regents of the Univ. of Cal. v. Eli Lilly & Co., 119 F.3d 1559, 1566 (Fed. Cir. 1997).
The court further opined that Centocor's suggestion
that our decision in Noelle and the PTO written description guidelines support the view that fully disclosing the human TNF-α protein provides adequate written description for any antibody that binds to human TNF-α. That suggestion is based on an unduly broad characterization of the guidelines and our precedent.
The court concluded that
While our precedent suggests that written description for certain antibody claims can be satisfied by disclosing a well-characterized antigen, that reasoning applies to disclosure of newly characterized antigens where creation of the claimed antibodies is routine. Claiming antibodies with specific properties, e.g., an antibody that binds to human TNF-α with A2 specificity, can result in a claim that does not meet written description even if the human TNF-α protein is disclosed because antibodies with those properties have not been adequately described.
With regard to the sequences recited in claim 18, it is well established (as evidenced by the teachings of Skolnick et al.), the art is unpredictable. Skolnick et al. (Trends in Biotechnology 18: 34-39, 2000) discloses the skilled artisan is well aware that assigning functional activities for any particular protein or protein family based upon sequence homology is inaccurate, in part because of the multifunctional nature of proteins (see, e.g., the abstract; and page 34, Sequence-based approaches to function prediction). Even in situations where there is some confidence of a similar overall structure between two proteins, only experimental research can confirm the artisan's best guess as to the function of the structurally related protein (see, in particular, the abstract and Box 2). Thus, one skilled in the art would not accept the assertion, which is based only upon an observed similarity in amino acid sequence that a variant of a given polypeptide would necessarily have a given biological activity. Moreover, protein chemistry is probably one of the most unpredictable areas of biotechnology. Consequently, the effects of sequence dissimilarities upon protein structure and function cannot be predicted. Bowie et al (Science, 1990, 257:1306-1310) teach that an amino acid sequence encodes a message that determines the shape and function of a protein and that it is the ability of these proteins to fold into unique three-dimensional structures that allows them to function and carry out the instructions of the genome and further teaches that the problem of predicting protein structure from sequence data and in turn utilizing predicted structural determinations to ascertain functional aspects of the protein is extremely complex (see column 1, page 1306). Bowie et al further teach that while it is known that many amino acid substitutions are possible in any given protein, the position within the protein's sequence where such amino acid substitutions can be made with a reasonable expectation of maintaining function are limited. Certain positions in the sequence are critical to the three-dimensional structure/function relationship and these regions can tolerate only conservative substitutions or no substitutions (column 2, page 1306). The sensitivity of proteins to alterations of even a single amino acid in a sequence are exemplified by Burgess et al (J. of Cell Bio. 111:2129-2138, 1990) who teach that replacement of a single lysine reside at position 118 of acidic fibroblast growth factor by glutamic acid led to the substantial loss of heparin binding, receptor binding and biological activity of the protein and by Lazar et al. (Molecular and Cellular Biology, 1988, 8:1247-1252) who teach that in transforming growth factor alpha, replacement of aspartic acid at position 47 with alanine or asparagine did not affect biological activity while replacement with serine or glutamic acid sharply reduced the biological activity of the mitogen. These references demonstrate that even a single amino acid substitution will often dramatically affect the biological activity and characteristics of a protein. Clearly, variant proteins based on any of the sequence recited in claim 8 that maintained the recited biological characteristics of the parent could not be predicted. Additionally, Bork (Genome Research, 2000,10:398-400) clearly teaches the pitfalls associated with comparative sequence analysis for predicting protein function because of the known error margins for high-throughput computational methods. Bork specifically teaches that computational sequence analysis is far from perfect, despite the fact that sequencing itself is highly automated and accurate (p. 398, column 1). One of the reasons for the inaccuracy is that the quality of data in public sequence databases is still insufficient. This is particularly true for data on protein function. Protein function is context dependent, and both molecular and cellular aspects have to be considered (p. 398, column 2). Conclusions from the comparison analysis are often stretched with regard to protein products (p. 398, column 3). Further, although gene annotation via sequence database searches is already a routine job, even here the error rate is considerable (p. 399, column 2). Most features predicted with an accuracy of greater than 70% are of structural nature and, at best, only indirectly imply a certain functionality (see legend for table 1, page 399). As more sequences are added and as errors accumulate and propagate it becomes more difficult to infer correct function from the many possibilities revealed by database search (p. 399, paragraph bridging columns 2 and 3). The reference finally cautions that although the current methods seem to capture important features and explain general trends, 30% of those features are missing or predicted wrongly. This has to be kept in mind when processing the results further (p. 400, paragraph bridging cols 1 and 2). Clearly, given not only the teachings of Bowie et al., Lazar et al. and Burgess et al. but also the limitations and pitfalls of using computational sequence analysis and the unknown effects of alternative splicing, post translational modification and cellular context on protein function as taught by Bork, the functional variants of the polypeptides of SEQ ID NO:8, 9, 10 or 11 cannot be predicted. Clearly, it could not be predicted that a polypeptide that is a “variant” of a given SEQ ID NO: will function in a given manner. Reasonable correlation must exist between structure and function.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 10-12, 14 and 17-21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Garbutt et al. (Journal of Dairy Science Vol. 80, pages 1512-1519 – IDS filed on 12-9-2022).
Garbutt et al. disclose Lactococcus lactis subsp. lactis strains with mutated phage infection protein (pip) which rendered them resistant to C2 bacteriophages (see abstract and page 1513). Garbutt et al. further disclose that two thirds of the mutated pip (including the C-terminal membrane anchoring region) was deleted (see page 1517). While Garbutt et al. do not explicitly disclose that said mutation results in increased nisin production, the disclosed “mutant” would necessarily have said ability.
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.
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 9-12, 14, 17-21 and 23-24 are rejected under 35 U.S.C. 103 as being unpatentable over Garbutt et al. (Journal of Dairy Science Vol. 80, pages 1512-1519 – IDS filed on 12-9-2022).
Garbutt et al. disclose Lactococcus lactis subsp. lactis strains with mutated phage infection protein (pip) which rendered them resistant to C2 bacteriophages (see abstract and page 1513). Garbutt et al. further disclose that two thirds of the mutated pip (including the C-terminal membrane anchoring region) was deleted (see page 1517). While Garbutt et al. do not explicitly disclose that said mutation results in increased nisin production, the disclosed “mutant” would necessarily have said ability.
Garbutt et al. differs from the rejected claims in that they don’t explicitly disclose the measurement of their Lactococcus lactis subsp. lactis mutant strains for nisin production. However, given that it is standard practice in laboratories to “characterize” mutant strains, it would have been obvious for one of ordinary skill in the art to measure nisin production.
Conclusion
No claim is allowed.
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/ROBERT A ZEMAN/Primary Examiner, Art Unit 1645 April 24, 2026
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