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 of Group 2 (claims 18, 21-27, 37-40, drawn to a method of reducing the risk of, preventing, or treating VRE colonization or infection, or modulating the subject’s microbiome) and the species of VREML237-2 (SEQ ID NO: 1) in the reply filed on 16 March 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
The Examiner agrees with applicant’s statement that an election for the second species does not apply to the subject matter of Group 2 (Remarks pg. 2).
Claim Status
The amended claim set filed 24 July 2024 is acknowledged. Claims 1, 5, 8, 18, 21-31, 34, and 37-40 are currently pending. Of those, claims 1, 8, 18, 21-30, and 34 are currently amended, and claims 37-40 are new. Claims 1, 5, 8, 28-31, and 34 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 16 March 2026. Claims 2-4, 6-7, 9-17, 19-20, 32-33, 35-36 are cancelled. Claims 18, 21-27, and 37-40 will be examined on the merits herein.
To improve clarity, references to the specification in this action will use paragraph numbers from the Pre-Grant Publication US-20240287468-A1, in order to avoid confusion if amendments to the specification change the page and line numbers where text is found.
Priority
The instant application claims priority to provisional application 63/210,555 (filed 15 June 2021) and is a 371 of PCT/IB2022/055508 (filed 14 June 2022). The effective filing date used for all claims is 15 June 2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 24 July 2024, 23 April 2025, 16 March 2026 were filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner. Signed copies of these statements are attached with this action.
Drawings
The drawings are objected to because: Figure 2 does not comply with 37 C.F.R. 1.84. Specifically, the text is not legible and does not comply with the following sections of the rule (emphasis added). See Examiner’s view of Figure 2 below.
“(a) Drawings. There are two acceptable categories for presenting drawings in utility and design patent applications.
(1) Black ink. Black and white drawings are normally required. India ink, or its equivalent that secures solid black lines, must be used for drawings; or
(p) Numbers, letters, and reference characters.
(1) Reference characters (numerals are preferred), sheet numbers, and view numbers must be plain and legible, and must not be used in association with brackets or inverted commas, or enclosed within outlines, e.g., encircled. They must be oriented in the same direction as the view so as to avoid having to rotate the sheet. Reference characters should be arranged to follow the profile of the object depicted.
(3) Numbers, letters, and reference characters must measure at least .32 cm. (1/8 inch) in height. They should not be placed in the drawing so as to interfere with its comprehension. Therefore, they should not cross or mingle with the lines. They should not be placed upon hatched or shaded surfaces. When necessary, such as indicating a surface or cross section, a reference character may be underlined and a blank space may be left in the hatching or shading where the character occurs so that it appears distinct.”
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Examiner’s view of Figure 2. Text is blurry and not legible. The smaller text may also be too small.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claim 18 is objected to because of the following informalities: Claim 18 is incomplete because it depends from a withdrawn claim. Appropriate correction is required.
Claim 40 is objected to because of the following informalities: Claim 40 the bacteria “L. acidophilus, L. rhamnosus, L. gasseri, L. reuteri, L. bulgaricus, L. plantarum, L. johnsonii, L. paracasei, L. casei, L. salivarius, L. lactis, B. bifidum, B. longum, B. breve, B. infantis, B. lactis, B. adolescentis”. The claim is incomplete because the bacteria genera “L” and “B” are not defined in the claims and multiple different bacterial genera begin with the letter “L” or “B”. The claim is not indefinite because the specification teaches that “L” is an abbreviation for Lactobacillus and “B” is an abbreviation for Bifidobacterium [0098], but the claims should be interpretable without reading the full specification. The genus need only be written out fully once, subsequent references can use the abbreviated form. Appropriate correction is required.
Claim Interpretation
Regarding claims 21 and 23-27, the claim recites phrases beginning with “optionally”. MPEP 2111.04 states: “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure.” The claim scope for examination is based only on the required elements of these claims.
Regarding claim 27, the claim recites “cream vaginal foam”. There is no comma and the plain meaning of the claim is that this is one object; this interpretation is also supported in the specification at [0014] using the same phrase. However, the instant specification also describes a cream and vaginal foam as being two different options in a list at [0119]. Applicant may wish to add a comma if the claim does not currently reflect their intent.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 21 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Regarding claim 21, the claim states “the subject is at risk of colonization or infection by VRE or is colonized or infected by VRE”. The specification does not specifically define subjects that are “at risk” but teaches that those at risk of colonization include non-immunocompromised subjects who come into contact with the bacteria [0006-0007]; therefore, the broadest reasonable interpretation is that any non-colonized subject is “at risk of colonization or infection by VRE”. Therefore, the claim recites that either the subject is not colonized with VRE and thus is at risk of colonization, or else the subject is colonized. The claim includes all possible subjects, and does not limit the parent claim. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements. In the interest of compact prosecution, it is noted that claim 22 already recites subjects that are colonized with VRE. So applicant might consider removing this subject matter from claim 21 and only claiming subjects that are at risk of colonization.
Claim Rejections - 35 USC § 112(a)
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.
Claims 18, 21-27, and 37-40 are rejected under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, 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 elected bacteriophage strain VREML237-2 (SEQ ID NO: 1) deposited with the ATCC under Accession Number PTA-126934 is required to practice the full scope of the claimed invention. In the interest of compact prosecution, it is noted that this argument would also apply to the non-elected, deposited bacteriophages. As such the biological material must be known and readily available or obtainable by a repeatable method set forth in the specification, or otherwise known and readily available to the public. If it is not so obtainable or available, the requirements of 35 USC 112(a) or pre-AIA 35 U.S.C. 112, first paragraph, may be satisfied by a deposit of the bacteriophage(s).
The process disclosed in the specification does not appear to be repeatable, it is not clear that the invention will work with commonly available material and it is not apparent if the biological materials considered necessary to make and use the invention is both known and readily available to the public. The claim recites administering the specific deposited bacteriophage, so one of ordinary skill in the art must have access to the deposited bacteriophage in order to practice the full scope claimed. Therefore, a deposit at a recognized depository may be made to obviate this rejection. It is noted that Applicants have deposited biological material but there is no indication in the specification as to public availability. The specification does not indicate whether or not the deposit was made under the terms of the Budapest Treaty.
If the deposit is made under the terms of the Budapest Treaty, then a statement, affidavit or declaration by Applicants, or by an attorney of record over his or her signature and registration number, or by someone in a position to corroborate the facts of the deposit, that the instant invention will be irrevocably and without restriction released to the public upon the issuance of a patent, would satisfy the deposit requirement made herein.
If the deposit is a non-Budapest Treaty deposit, then in order to certify that the deposit meets the requirements set forth in 37 CFR 1.801-1.809 and MPEP 2402-2411.05, a statement, affidavit or declaration by Applicant or by an attorney of record over his or her signature and registration number, or by someone in a position to corroborate the facts of the deposit would satisfy the requirements herein by stating and providing that:
(a) During the pendency of the application, access to the invention will be afforded to the Commissioner upon request;
(b) All restrictions upon availability to the public will be irrevocably removed upon granting of the patent;
(c) The deposit will be maintained in a public depository for a period of 30 years, or 5 years after the last request or for the enforceable life of the patent, whichever is longer; and
(d) Provide evidence of the test of the viability of the biological material at the time of deposit (see 37 CFR 1.807).
Claims 18, 21-27, and 37-40 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.
When evaluating the specification in the context of the prior art at the time of filing, one having ordinary skill in the art at the time of filing would have concluded that the specification demonstrated possession of methods of reducing the risk of, or preventing, or treating VRE colonization or infection in a subject in need thereof comprising administering to the subject one of the bacteriophages of SEQ ID NOs: 1-5, or variant bacteriophages having at least 90% gANI, but have not demonstrated possession of methods for modulating a human subject's microbiome or methods that use bacteriophages that have less than 90% gANI to one of SEQ ID NOs: 1-5 and that do not have the same properties as the described bacteriophages. The rationale for this conclusion follows.
MPEP 2163 states:
An original claim may lack written description support when (1) the claim defines the invention in functional language specifying a desired result but the disclosure fails to sufficiently identify how the function is performed or the result is achieved or (2) a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349-50 (Fed. Cir. 2010) (en banc). The written description requirement is not necessarily met when the claim language appears in ipsis verbis in the specification. "Even if a claim is supported by the specification, the language of the specification, to the extent possible, must describe the claimed invention so that one skilled in the art can recognize what is claimed. The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement." Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002).
Thus, the written description requirement may be satisfied through disclosure of function and minimal structure when there is a well-established correlation between structure and function. In contrast, without such a correlation, the capability to recognize or understand the structure from the mere recitation of function and minimal structure is highly unlikely. In this latter case, disclosure of function alone is little more than a wish for possession; it does not satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (written description requirement not satisfied by merely providing "a result that one might achieve if one made that invention"); In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming a rejection for lack of written description because the specification does "little more than outline goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate").
The claims are drawn to methods of reducing the risk of, or preventing, or treating VRE colonization or infection in a subject in need thereof, or for modulating a human subject's microbiome, comprising administering to the subject an isolated bacteriophage according to claim 1 or a progeny thereof. The elected bacteriophage of claim 1 is “An isolated bacteriophage that infects and lyses one or more strains of vancomycin-resistant Enterococci (VRE), wherein the bacteriophage is of a strain selected from:(i) bacteriophage strain VREML237-2 (SEQ ID NO: 1) deposited with the ATCC under Accession Number PTA- 126934, or a variant strain thereof, wherein the variant strain has an average nucleotide identity across its genome (gANI) of at least 80% to said bacteriophage strain VREML237-2;”.
Therefore, the broadest reasonable interpretation of the claim is that the bacteriophage can have less than 80% gANI relative to the deposited bacteriophage genome because the limitation “or progeny thereof” does not place any limits on what modifications can be made to the progeny phages. Also, the broadest reasonable interpretation of “modulating a human subject's microbiome” is broader than only modulating VRE levels and also includes other modulations of other species. In order to describe the method, the specification must describe how to select which bacteriophages from this group of phages with unlimited genetic modifications that are capable of use for reducing the risk of, or preventing, or treating VRE colonization or infection in a subject in need thereof, and for modulating a human subject's microbiome.
The specification teaches that there has not been a commercially manufactured phage product targeting VRE, and that “little research was conducted” in the U.S. and Western Europe, though it continued to be used in Eastern Europe [0004]. The specification teaches “Typically, scholars would identify organisms with a gANI≥95% as belonging to the “Same Species.” … A variant strain having at least 90% gANI to the reference strain is presumed and deemed to have the same phenotypic characteristics as said reference bacteriophage strain.” [0044]. In other words, the specification teaches that the scope of bacteriophages claimed (variants with at least 80% gANI, progeny that can have even more genetically dissimilar) are not all considered to be the “same species” and are not “presumed and deemed to have the same phenotypic characteristics as said reference bacteriophage strain”.
The examples of the specification demonstrate an anti-VRE effect for five bacteriophages: VREML237-2 (SEQ ID NO: 1, the elected bacteriophage species), as well as the non-elected species VREML110-1 (SEQ ID NO: 2), VREML 105 (SEQ ID NO: 3), VREML202-1 (SEQ ID NO: 4), and VREML85-2 (SEQ ID NO: 5) [Tables 1-2]. The anti-VRE effect is demonstrated for individual bacteriophages [Table 1-2] and for a cocktail comprising all five bacteriophages [0171, 0177]. Example 6 states this “five-phage cocktail” [0175] can reduce VRE gastrointestinal colonization in a mouse model, when the cocktail is administered after VRE colonization [0175]; no data is presented but the experiments leading to the conclusion were described [0176]. Example 7 states this cocktail can reduce VRE burden in a human gut microbiome model, when the cocktail is administered prior to VRE colonization.; however, the data in Figure 2 cannot be interpreted to support this statement. Example 7 also states that the phage cocktail stimulated microbial recovery after antibiotic treatment in two of three samples [0179]; however, there is no data presented to support this claim and the specification does not explain what data was collected and how it was analyzed in order to reach this conclusion. Example 8 appears to be prophetic and describes trials that could be performed in the future.
The specification also teaches that the function of infecting and lysing VRE is not associated with genetic relatedness in bacteriophages. The phages with genomes of SEQ ID NOs: 1-2 both have this function, but have little to no genetic relatedness. Aligning the first 15,000 nucleotides of each sequence resulted in two potential matches, both with 0.2% query match.
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In summary, the working examples teach that each of the bacteriophages with SEQ ID NOs: 1-5 individually antagonize VRE, and that the cocktail comprising them is capable of both prevention and treatment of VRE colonization or infection. The specification also states that bacteriophages with 90% gANI or more are presumed to have the same properties, but below this limit, the function of infecting and lysing VRE is not correlated with genetic relatedness as measured by gANI. Also, there is no data or explanation supporting the structure of the phages being correlated with the function of modulating the subject’s microbiome, other than reducing the level of VRE present.
MPEP 2163 states: “An invention described solely in terms of a method of making and/or its function may lack written descriptive support where there is no described or art-recognized correlation between the disclosed function and the structure(s) responsible for the function.” In this case, the bacteriophages useful for the method are described by being capable of functions: “infects and lyses one or more strains of vancomycin-resistant Enterococci (VRE)” from claim 1, “reducing the risk of, or preventing, or treating VRE colonization or infection in a subject in need thereof” from claim 18, and “for modulating a human subject's microbiome” also from claim 18. However, the method administers bacteriophages with less than 90% gANI that cannot be presumed to have the same function as the tested bacteriophages. The specification does not identify any structures correlated with the claimed functions, other than being one of the five bacteriophages tested in the examples, or having greater than 90% gANI with one of the five bacteriophages tested in the examples.
The specification also does not identify any structures associated with the broader scope of “modulating a human subject’s microbiome”, the assertion of a method capable of achieving this effect by administering the bacteriophages claimed appears to be a mere wish for possession that does not satisfy the written description requirement.
The specification is not required to teach features that were well known in the art at the time of filing. From MPEP 2163: “What is conventional or well known to one of ordinary skill in the art need not be disclosed in detail. See Hybritech Inc. v. Monoclonal Antibodies, Inc., 802 F.2d at 1384, 231 USPQ at 94. See also Capon v. Eshhar, 418 F.3d 1349, 1357, 76 USPQ2d 1078, 1085 (Fed. Cir. 2005).” Hazan and Beyth (US-20170281700-A1; hereafter Hazan; PTO-892) is a similar patent application using bacteriophages to treat or prevent an infection caused by Enterococcus species [Abstract], and is cited to demonstrate what was conventional in this field at the time of filing. Hazan describes bacteriophage variants having at least 95% genome identity, corroborating the specification’s statement that this level of relatedness is generally considered in the art to be the “same species” and have the same properties. Hazan’s process of isolating anti-Enterococcus bacteriophages [Example 1 beginning 0130] is similar to that used in the instant specification. Hazan also performs genome sequencing on the bacteriophages [Example 4 beginning 0141]. However, in Hazan’s experiments using the bacteriophages to treat VRE [Example 6 beginning 0152] or E. faecalis [Example 5 beginning 0150], the conclusions about the experimental results [0153 or 0151, respectively] are supported by the presence of figures displaying the data [Figure 5 A-B or Figures 4B-D, respectively] and by discussing the specific outcomes that were observed. One of ordinary skill in the art at the time of filing would recognize that unsupported assertions about experimental results are less convincing compared to the data and detail provided by Hazan.
When evaluating the specification in the context of the prior art at the time of filing, one having ordinary skill in the art at the time of filing would have concluded that the specification demonstrated possession of methods of reducing the risk of, or preventing, or treating VRE colonization or infection in a subject in need thereof comprising administering to the subject one of the bacteriophages of SEQ ID NOs: 1-5, or variant bacteriophages having at least 90% gANI, but have not demonstrated possession of methods for modulating a human subject's microbiome or methods that use bacteriophages that are less than 90% related and that do not have the same properties as the described bacteriophages. Therefore, claims 18, 21-27, and 37-40 are rejected as lacking adequate written description.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMELIA N DICKENS whose telephone number is (571)272-0381. The examiner can normally be reached M-F 8:30-4:30 (EDT/EST).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached at (571) 270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/AMELIA NICOLE DICKENS/Examiner, Art Unit 1645
/SAMIRA J JEAN-LOUIS/Supervisory Patent Examiner, Art Unit 1642
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