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 .
Election/Restrictions
Applicant's election with traverse of Group II (claims 9-14) in the reply filed on 11/10/2025 is acknowledged. The traversal is on the following grounds.
First, applicant asserts that the NCBI disclosure of the complete genome of “Listeria virus P100plus” is not sufficient because “a sequence is a string of data representing the nucleotides present in a nucleic acid”, a sequence is thus “an intangible asset” and “a genome is not a bacteriophage” (Remarks, p. 6, par. 3).
Second, applicant asserts that the document constitutes an exception under 35 U.S.C. § 102(b)(1)(A).
Applicant’s arguments have been fully considered but are not persuasive for the following reasons.
With respect to the first argument, the examiner disagrees with the assertion. The NCBI document discloses not only the existence of “Listeria virus P100plus” but also provides its entire genome. This is sufficient structure to meet the disclosure requirement. There is no requirement that the prior art disclose all of the properties and characteristics of the bacteriophage; the only question is whether the linking feature was known publicly before the effective filing date. And although it is not necessary to sustain the restriction requirement, it is noted that a person having ordinary skill in the art could easily see exactly how the P100+ bacteriophage differs from P100. For example, the NCBI disclosure annotates specific proteins such as “receptor binding protein” which has the E97K, E104D, and Y131H mutations relative to P100’s receptor protein (see pages 12-13 of the NCBI document provided in the IDS filed on 03/27/2023). Moreover, the claims define the structure of the bacteriophage by precisely the DNA sequence (SEQ ID NO: 1) which applicant regards as an “intangible asset” and it is therefore unclear what additional details applicant believes would be sufficient to publicly disclose the P100+ bacteriophage when their own invention is defined by this same standard.
With respect to the second argument, although applicant has invoked the 102(b)(1)(A) exception, this exception is relevant only to rejection under §§ 102/103 and is not relevant to the § 371 determination of unity of invention.
For at least these reasons, the unity of invention requirement is still deemed proper and is therefore made FINAL.
Claims 1-8 and 15 are not directed to the elected invention and have been withdrawn.
Claims 9-14 are directed to the elected invention and have been examined on their merits.
Priority
The present application is a § 371 national stage entry of PCT/EP2021/076894 (filed on 09/30/2021) and claims priority to foreign application EP20199513.1 (filed on 10/01/2020).
Information Disclosure Statement
The listing of references in p. 16 of 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.
Claim Interpretation
Claim 9 refers to “Listeria serovar 1/2*” (through incorporation of the language of claim 1). 1/2* is not a term of art. However, it is noted that the specification explicitly defines “1/2*” as meaning strains which have lost the N-acetylglucosamine on the cell-wall teichoic acids, which lead to bacteriophage resistance (specification, p. 1, lines 34-37). Thus, “serovar 1/2*” is interpreted to refer to serovar 1/2 Listeria which lack GlucNac on their cell-wall teichoic acids and there therefore otherwise resistant to bacteriophage infection. This is also shown in Figure 1 of the drawings.
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 - This application fails to comply with the requirements of 37 CFR 1.821 - 1.825 because it does not contain a "Sequence Listing" as a separate part of the disclosure or a CRF of the “Sequence Listing.”.
Required response - Applicant must provide:
A "Sequence Listing" part of the disclosure; together with
An amendment specifically directing its entry into the application in accordance with 37 CFR 1.825(a)(2);
A statement that the "Sequence Listing" includes no new matter as required by 37 CFR 1.821(a)(4); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(a)(3).
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) c) or d) above, applicant must also provide:
A CRF in accordance with 37 CFR 1.821(e)(1) or 1.821(e)(2) as required by 1.825(a)(5); and
A statement according to item 2) a) or b) above.
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.
Claims 9-14 are rejected under 35 U.S.C. 112(a), as failing to comply with the enablement requirement.
The claims contain 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.
The specification lacks complete deposit information for the deposit of the P100+ and P200 bacteriophages covered by the scope of the claim. Applicant’s disclosure states that bacteriophages P100+ and P200 were deposited under accession numbers CBS146750 and CBS146751 (specification, p. 3, lines 23-27). Because it is not clear that the bacteriophages can be isolated from nature without undue experimentation and because the best mode disclosed by the specification requires the use of these specific bacteriophages, a suitable deposit for patent purposes is required.
Applicant’s specification states that the deposits were made under the provisions of the Budapest Treaty (specification, p. 12, lines 34-37).
If the deposit has been made under the provisions of the Budapest Treaty, the deposit requirement may be fulfilled by filing an affidavit or declaration by applicants or assignees or a statement by an attorney of record who has authority and control over the conditions of the deposit over his or her signature and registration number averring that:
the deposit was made under the Budapest treaty and “all restrictions imposed by the depositor on the availability to the public of the deposited material will be irrevocably removed upon the granting of the patent”.
This requirement is necessary when deposits are made under the provisions of the Budapest Treaty as the Treaty leaves this specific matter to the discretion of each State.
If the deposit was made after the effective filing date of the application for patent in the United States, a verified statement is required from a person in a position to corroborate that the cell line described in the specification as filed is the same as that deposited in the depository. Corroboration may take the form of a showing of a chain of custody from applicant to the depository coupled with corroboration that the deposit is identical to the biological material described in the specification and in the applicant's possession at the time the application was filed.
Applicant's attention is directed to In re Lundak, 773 F.2d. 1216, 227 USPQ 90 (CAFC 1985) and 37 CFR § 1.801-1.809 for further information concerning deposit practice.
Claims 9-14 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement.
The claims contain 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 at the time the application was filed, had possession of the claimed invention.
Claim 9 is broadly directed to a method comprising “contacting a bacteriophage or a combination of bacteriophages according to claim 1, or a composition comprising said bacteriophage or comprising said combination of bacteriophages, to a food product or to food processing equipment to reduce the amount of Listeria”.
The bacteriophage according to claim 1 is:
“A bacteriophage lytic for at least Listeria serovar 1/2* and/or serovar 3, wherein said bacteriophage has a genome that has at least 70% sequence identity with the bacteriophage P100 as set forth in SEQ ID NO: 1, and wherein the distal part of the receptor protein as set forward in SEQ ID NO: 4 has at least one mutation selected from: G157R, E97K, E104D and Y131H”.
Therefore, the scope of the claims broadly allows for the use of any bacteriophage having at least one mutation recited in claim 1 and having at least 70% sequence identity with the bacteriophage P100.
In order to satisfy the written description requirement for applicant’s broad claim to a method of using any bacteriophage having the at least one mutation and having at least 70% sequence identity with the bacteriophage P100, applicant must disclose sufficiently detailed, relevant identifying characteristics. These characteristics include the complete or partial structure, other physical or chemical properties, or functional characteristics when coupled with a known or disclosed correlation between function and structure. Additionally, applicant may meet this requirement by sufficiently describing a representative number of species within the claimed genus.
Klumpp et al. (Bacteriophage, 2013, vol. 3(3), pages 1-8) teaches that Listeria serovars 1/2 are particularly susceptible to phage infection and no phages have been reported for serovar 3 strains which are highly refractory to phage infection (p. 1, right col., par. 1-3). Applicant has disclosed two sets of mutations (E97K or E97K, E104D, and Y131H) which enhance the host range of P100 and A511 to include lytic activity against Listeria 1/2* and 3 serovars. Accordingly, applicant has disclosed two bacteriophages (P100+ and P200) among the large group of bacteriophages having at least 70% sequence identity to SEQ ID NO: 1 (i.e., any bacteriophage differing by as many as 39,415 bases). And although it is acknowledged that applicant has demonstrated the enhanced host range by testing variants of two bacteriophages (P100 and A511), this is not sufficient to meet the disclosure requirement for every bacteriophage covered by the breadth of applicant’s claims because applicant has only disclosed two bacteriophages which are very similar in sequence identity and characteristics. For example, Klumpp teaches that the genomes of A511 and P100 are “very similar” and “morphologically indistinguishable”, with “strong sequence homologies” (p. 3, right col., par. 2). Klumpp further teaches that A511 is a “close relative” of P100 (p. 5, right col., par. 2). Thus, when considering the breadth of the groups actually disclosed by the specification, applicant has only demonstrated possession of a mutant of P100 and its close relative and a person having ordinary skill in the art would not clearly recognize applicant’s possession of a representative number of Listeria phages from the large group of phages having “at least 70%” sequence identity to SEQ ID NO: 1.
For at least these reasons, applicant’s disclosure does not satisfy the written description requirement.
Claims 10-14 depend from claim 9 and do not substantially narrow the breadth of the claims such that one skilled in the relevant art that the inventor at the time the application was filed would recognize applicant’s possession of the claimed invention.
Claims 9-14 are rejected under 35 U.S.C. 112(a) because the specification, while being enabling for controlling contamination in a food product with some compositions, does not reasonably provide enablement for doing the same with all compositions covered by the scope of the claims.
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.
The factors considered when determining if there is sufficient evidence to support that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue” include, but are not limited to: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. See In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). MPEP § 2164.04
further states that although the analysis and conclusion of a lack of enablement are based on these factors and the evidence as a whole, it is not necessary to discuss each factor in the enablement rejection.
With respect to the breadth of the claims and the nature of the invention, the claims are so broad as to encompass the use of any bacteriophage or combination of bacteriophages according to claim 1. The bacteriophage according to claim 1 is “a bacteriophage lytic for at least Listeria serovar 1/2* and/or serovar 3, wherein said bacteriophage has a genome that has at least 70% sequence identity with the bacteriophage P100 as set forth in SEQ ID NO: 1, and wherein the distal part of the receptor protein as set forward in SEQ ID NO: 4 has at least one mutation selected from: G157R, E97K, E104D and Y131H”. Claims 10-14 are limiting to the food products and methods of spraying.
With respect to the state of the prior art, the prior art does not previously acknowledge the potential for “at least one mutation” selected from G157R, E97K, E104D, and Y131H to cause a bacteriophage to by lytic for Listeria serovars 1/2* and 3. Klumpp et al. (Bacteriophage, 2013, vol. 3(3), pages 1-8) teaches that no phages have been reported for serovar 3 strains which are highly refractory to phage infection (p. 1, right col., par. 1-3). MT178766 (cited previously) discloses the existence of bacteriophage P100+ but does not disclose the enhancement of host range due to its differences from P100. Similarly, MT178767 (cited in the IDS filed on 03/27/2023) discloses the existence of bacteriophage P200 but does not disclose the enhancement of host range.
With respect to the amount of direction provided by the inventor and the existence of working examples, applicant teaches a change from glutamic acid to lysine at position 97 yielded variant P100+ (specification, p. 16, lines 9-10 and 14) and additional changes from glutamic acid to aspartic acid at position 104 (E104D) and from tyrosine to histidine at position 131 (Y131H) yielded variant P200 (specification, p. 16, lines 12-15). Applicant teaches that these modifications altered the host ranges of A511 and P100 bacteriophages such that they were capable of lysing Listeria serovars 1/2* and 3. Applicant’s disclosure makes no mention of the effect of the G157R mutation.
With respect to the level of one of ordinary skill, a person having ordinary skill in the art is a person having an advanced understanding of microbiology or virology.
With respect to the level of predictability and the quantity of experimentation needed, there is a low level of predictability (and conversely a high level of experimentation) needed to enable the invention when the at least one mutation is G157R, E104D, or Y131H. As discussed above, there is no previous disclosure that such a mutation elicits any effect on the host range of Listeria bacteriophages and the specification provides no indication as to what/if any effect is derived from the G157R mutation (e.g., does this change improve the host range such that 1/2* serovars are infected by the modified bacteriophage? What about serovar 3? or both?) Because it was previously known that strains such as serovar 3 strains are “highly refractory to phage infection”, there is a low level of predictability that this single amino acid mutation would elicit an enhanced host range. Moreover, the specification makes clear that E104D and Y131H are required in addition to E97K and there is no evidence that a single E104D or Y131H would elicit the enhanced host range. Applicant’s specification makes clear that all three mutations are required by stating “[t]he ability to recognize SV 1/2* as observed in P100+ requires two (additional) changes” (p. 16, lines 9-15).
Thus, there would be an undue amount of experimentation needed to determine which (if any) “at least one” mutation imparts the enhanced host range. This experimentation would encompass generation of genetic mutants of each and every bacteriophage having a genome that has at least 70% sequence identity with the genome of bacteriophage P100 to determine if it possess the ability to lyse serovars 1/2* and 3 when contacted to a food product or to food processing equipment.
Conclusion: Upon consideration of the Wands’ factors and the evidence as a whole, the invention is enabled when the at least one mutation is 1) E97K (for serovar 3) or 2) E97K, E104D, and Y131H (for serovars 1/2*) but the invention is not enabled when the “at least one mutation” is G157R, E104D, or Y131H alone.
Pertinent Prior Art
A prior art rejection has not been made over claims 9-14. Although the examiner maintains that the MT178766 genome is sufficient disclosure of the P100+ bacteriophage (as discussed in the Election/Restrictions section above), this disclosure was made publicly available on April 22, 2020. As discussed in applicant’s remarks dated 11/10/2025, the disclosure was made within the one-year grace period and by the sole inventor on the present application, Mr. Steven Hagens. As such, the GenBank deposit constitutes an exception under 35 U.S.C. § 102(b)(1)(A) and is not available prior art for §§ 102 and 103. Similarly, the P200 genome was disclosed on the same day and by the inventor of the present application. Therefore, based upon applicant’s previous statement that these GenBank disclosures were made by the sole inventor on this application, they are not available as prior art pursuant to 35 U.S.C. § 102(b)(1)(A).
Klumpp et al. (Bacteriophage, 2013, vol. 3(3), pages 1-8), teaches the existence of dozens of bacteriophages (p. 2-3) and teaches that P100 and A511 have been used to “very effectively reduce Listeria contamination” when applied to ready-to-eat foods, in packaging, and on food preparation surfaces (p. 5, right col., par. 1-4). Klumpp does not teach or suggest bacteriophages having a genome having at least 70% sequence identity with the genome of bacteriophage P100 and having at least one mutation selected from G157R, E97K, E104D, and Y131H in the distal part of the receptor binding protein set forth in SEQ ID NO: 4 let alone their use in a method for controlling Listeria contamination in a food product, on food processing equipment or on food storage containers.
Loessner (WO 2007093849; cited in IDS filed on 03/27/2023) teaches the application of bacteriophage P100 to food products and food processing equipment (p. 23, lines 9-17) and although Loessner also teaches the use of variants of the P100 phage (p. 7, lines 6-25), it does not teach or suggest the specific amino acid changes recited in claim 1 nor does it suggest that such mutations would be useful for enhancing the host range of P100 such that it is now lytic for Listeria 1/2* and 3 serovars.
Conclusion
No claim is allowed.
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/GRANT C CURRENS/Examiner, Art Unit 1651