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 of Group II, claims 1, 2, 9, 11, 24-29, and 41, and the required species: A) ECML-123-2, B), IBD, C) oral dosage form, and D) gastric acid reducing agent, in the reply filed on 7/6/2026 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)).
Claims 2, 11, and 27-29 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 7/6/2026.
Claims 1, 9, 24-26, and 41 are under examination on the merits.
Information Disclosure Statement
The Information Disclosure Statements (IDSs) submitted on 5/1/2024, 4/27/2026, and 8/25/2026 are in compliance with 37 CFR 1.97. Accordingly, the references listed in the IDSs are being considered by the examiner.
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.
Claim Objections
Claim 1 is objected to because of the following informalities: claim 1 recites “a method of reducing the risk of, or preventing, or treating AIEC colonization or infection” on lines 1-2, but does not spell out “adherent-invasive Escherichia coli” until line 7. “AIEC” on line 2 should instead read “adherent-invasive Escherichia coli (AIEC)”. Appropriate correction is required.
Claim 1 is objected to because of the following informalities: claim 1 recites “a lytic infection” on line 7, but should instead recite “a lytic phage infection”. Appropriate correction is required.
Claim 24 is objected to because of the following informalities: claim 24 recites “wherein the subject is suffering from an inflammatory bowel disease (IBD)” on lines 1-2, but should instead read “wherein the subject has an inflammatory bowel disease (IBD)”. Appropriate correction is required.
Claim Interpretation
The specification indicates that AIEC infection refers to AIEC invasion of the subject’s tissue that is causing disease in the subject, and “preventing” means to reduce the risk of AIEC colonization or infection or prevent AIEC colonization or infection, or to reduce the level of AIEC colonization or infection, in a subject in need thereof (spec., para. [0042]). “Colonization” refers to the presence of AIEC in a subject that is not necessarily causing disease in the subject (spec., para. [0041]).
Thus, the examiner is interpreting “infection” in the claims to mean that it is an AIEC invasion that is already causing disease. The examiner is interpreting vaccination such that the preventing part of it is held to the definition of the specification, meaning to reduce the risk of AIEC colonization or infection or preventing AIEC colonization or infection, or to reduce the level of AIEC colonization or infection, in a subject in need thereof.
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.
Scope of Enablement
Claims 1, 9, and 24-26 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating inflammatory bowel disease (IBD), comprising administering to a subject a bacteriophage composition comprising the bacteriophage strain ECML-123-2, does not reasonably, does not reasonably provide enablement for a method of treating inflammatory bowel disease (IBD), comprising administering to a subject a bacteriophage composition comprising a variant strain of bacteriophage strain ECML-123-2 that has at least 80% average nucleotide identity across its genome to ECML-123-2. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
The breadth of the claims is found in claim 1.
The nature of the invention is a method of treating inflammatory bowel disease (IBD) in a subject in need thereof, comprising administering to the subject a bacteriophage composition comprising a bacteriophage strain capable of producing a lytic infection in an adherent-invasive Escherichia coli strain, and a pharmaceutically acceptable carrier, wherein the bacteriophage strain is strain ECML-123-2 deposited with the ATCC under Accession Number PTA-121408, or a variant strain thereof, wherein the variant strain has at least 80% average nucleotide identity across its genome (gANI) to said bacteriophage strain ECML-123-2.
The level of skill of one skilled in this art is high.
The specification teaches that phage ECML-123-2 is lytic to a number of AIEC strains (paras. [0127-128] and Example 3, and that a seven phage cocktail comprising ECML-123-2 prevented death in a treated group of mice infected with an AIEC strain (paras. [0135-0150], Group 3, high phage cocktail dose).
The state of the prior art is such that bacteriophage strains capable of producing a lytic infection in an adherent-invasive E. coli strain may be utilized to treat IBD (Danglas, et al. PGPub US20160143865A1, published 5/26/2016; Abstract).
It is well established in the art that protein chemistry is an unpredictable areas of biotechnology. For example, conservative replacement of a single “lysine” residue 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 (Burgess et al., J of Cell Bio. 111:2129-2138, 1990). 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 (Lazar et al. Molecular and Cellular Biology 8:1247-1252, 1988). As these references illustrate, it is unpredictable that a polypeptide variant of a known target protein binder will also bind said target. It is also unpredictable that they would bind said target in the same way, having the same effect on the target (i.e. inhibit or activate). Ju (Proceedings of the National Academy of Sciences, U.S.A., Vol. 88, Pg. 2658-2662, 1991) teaches that the interleukin 1 receptor (IL-1R) antagonist IL-1ra is a naturally occurring protein with no agonist activity in vitro or in vivo (Abstract). However, substitution of a single amino acid lysine145 to aspartic acid changes the property of this peptide to a partial agonist of IL-1R (Abstract). Thus, even a single substitution can change the biological property of a peptide.
This substitution need not be at a position where said residue would contact the target protein. Baker (Immunity, Vol. 13, Pg. 475-484, 2000) teaches that Tax-peptide is an agonist of the of T cell activity (Abstract). However, mutation of proline at position 6 of this peptide to alanine creates a T cell antagonist (Abstract). Importantly, this residue does not contact the T cell receptor (Abstract).
In another case, Huang (The Journal of Biological Chemistry, Vol. 272, No. 43, Pg. 27155-27159, 1997) teaches that conjugation of peptides to other proteins can change their biological properties. They teach that multiple conjugation of the peptide TGFβ1 (residues 41-65) to carrier proteins enhances its antagonist activity but also confers partial agonist activity as well (Abstract). Thus, the chemical context of a biologically active peptide is also important.
Truncation of proteins can also lead to adverse effects on protein structure and thus protein function. Martindale (Nature Genetics, Vol. 18, Pg. 150-154, 1998) teaches that truncation of huntingtin leads to aggregate development which compromises cell viability (Abstract). Nonaka (Human Molecular Genetics, Vol. 18, No. 18, Pg. 3353-3364, 2009) teaches that truncation of TDP-43 to its C-terminal fragments causes abnormally phosphorylated and ubiquitinated inclusions of the protein (Abstract). Taken together, not just any truncation of a protein will yield a soluble, functional, protein fragment.
In summary, these examples teach that the biological function of peptide variants is unpredictable because even a single mutation can abolish activity or give a different function. For example, agonist and antagonist peptides can be interconverted through conjugation or mutagenesis. Importantly, binding can still occur after mutation or conjugation in the literature examples provided above, illustrating that a simple show of binding is not predictive of the nature of a peptide’s biological activity. This point is underlined by Montrose-Rafizadeh (The Journal of Biological Chemistry, Vol. 272, Pg. 21201-21206, 1997) who teaches that receptor binding does not predict agonist or antagonist activity (Pg. 21205, Column 2, Paragraph, first full, Sentence, first).
With respect to the use of peptides in the treatment of a disease, the state of the art at the time of filing was such that it was unpredictable whether or not a peptide would function therapeutically. Their functionality depends, in part, on whether or not they reach their intended target in a sufficient quantity as to cause a therapeutic effect. Mendoza (Arch. Immunol. Ther. Exp., Vol. 53, Pg. 47-60, 2005) teaches that peptides derived from larger molecules that are important modulators of apoptosis are frequently becoming leads for the development of anticancer therapeutics (Pg. 48, Column 2, Paragraph, first partial). However, they also state that natural peptides have low bioavailability and short half-life in the mammalian circulation system, while synthetic peptides have potential cytotoxicities (Pg. 57, Column 1, Paragraph, last full). Due to these characteristics, systematic testing in in vivo as well as in vitro settings must be done rigorously to verify peptide applications in the clinic (Pg. 57, Column 1, Paragraph, last full). Taken together, barring experimental evidence, no peptide can merely be assumed to function in the treatment of a disease, in vivo just because it functions as an inhibitor in vitro.
Since the art teaches that it is unpredictable whether or not peptide variants of known inhibitors will function as such and it is also unpredictable that even a known inhibitory peptide that functions in vitro will function in vivo, and the specification does nothing to ameliorate these concerns, one would be burdened with undue experimentation to use the products of instant claims as broadly as they are currently claimed.
Thus, the state of the art recognized that it would be highly unpredictable that a mutated bacteriophage strain ECML-123-2 would be capable of lysing AIEC, because one or many genes (and the proteins that the genes encode) could be mutated and dysfunctional. One of skill in the art would neither expect nor predict the appropriate functioning of the nucleic acid molecule or products that it encodes when mutated.
In view of the lack of the predictability of the art to which the invention pertains as evidenced by Burgess, Baker, Ju, Lazar, Huang, Martindale, Montrose, Nonaka, and Mendoza, the lack of guidance and direction provided by applicants, and the absence of working examples, undue experimentation would be required to make and use bacteriophage strain ECML-123-2 that is mutated with a reasonable expectation of success, absent a specific and detailed description in applicant’s specification of how to effectively practice this and absent working examples providing evidence which is reasonably predictive that the claimed bacteriophages are functional, commensurate in scope with the claimed invention.
Not knowing, absent further experimentation, which modifications function and which do not, when, as set forth above, even a single change of an encoded amino acid can unpredictably affect bacteriophage structure and function, leads to one having no predictability or expectation of success for the function of any given bacteriophage modification. Such random experimentation to identify at a later time what structure or fragment or modification is or is not functional and is embraced by Applicant’s claims is undue experimentation. This affects all claims that can mutate or truncate the claimed bacteriophage, for example claims 1, 9, and 24-26.
Moreover, claims not containing elements critical or essential to the practice of the invention, such as bacteriophage, which may be broadly mutated or truncated, are not enabled by the disclosure. See In re Mayhew, 527 F.2d 1229, 188 USPQ 356 (CCPA 1976).
Note that an enabling disclosure for the preparation and use of only a few analogs of a product does not enable all possible analogs where the characteristics of the analogs are unpredictable. See Amgen Inc. v. Chugai Pharmaceutical Co. Ltd. (18 USPQ 2d 1027 (CAFC 1991)).
Claims 41 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating AIEC infection comprising administering to the subject a bacterial lysate obtained by lysing an AIEC strain with an isolated bacteriophage of strain ECML-123-2 deposited with the ATCC under Accession Number PTA-121408, does not reasonably provide enablement for a method of vaccinating a subject against AIEC infection, comprising administering to the subject a bacterial lysate obtained by lysing an AIEC strain with an isolated bacteriophage of strain ECML-123-2 deposited with the ATCC under Accession Number PTA-121408. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
The breadth of the claims is found in claim 41.
The nature of the invention is a method for vaccinating a subject against AIEC infection, comprising administering to the subject a bacterial lysate obtained by lysing an AIEC strain with an isolated bacteriophage of strain ECML-123-2 deposited with the ATCC under Accession Number PTA-121408.
The level of skill of one skilled in this art is high.
The specification indicates that AIEC infection refers to AIEC invasion of the subject’s tissue that is causing disease in the subject, and “preventing” means to reduce the risk of AIEC colonization or infection or prevent AIEC colonization or infection, or to reduce the level of AIEC colonization or infection, in a subject in need thereof (spec., para. [0042]). “Colonization” refers to the presence of AIEC in a subject that is not necessarily causing disease in the subject (spec., para. [0041]).
Thus, the examiner is interpreting “infection” in the claims to mean that it is an AIEC invasion that is already causing disease. The examiner is interpreting vaccination such that the preventing part of it is held to the definition of the specification, meaning to reduce the risk of AIEC colonization or infection or preventing AIEC colonization or infection, or to reduce the level of AIEC colonization or infection, in a subject in need thereof. The specification does not provide any examples of preventing or reducing the risk of AIEC getting into the body, and that is all colonization requires under the definitions of the specification.
The specification teaches that phage ECML-123-2 is lytic to a number of AIEC strains (paras. [0127-128] and Example 3, and that a seven phage cocktail comprising ECML-123-2 prevented death in a treated group of mice infected with an AIEC strain (paras. [0135-0150], Group 3, high phage cocktail dose). The specification does not provide any examples of the phage ECML-123-2 deposited with the ATCC under Accession Number PTA-121408 preventing AIEC infection. There is no mechanism provided by the disclosure that would enable one of ordinary skill in the art to do so.
The state of the art is such that in a murine model of induced colitis of animals infected with the AIEC strain LF82, a single dose of a cocktail of phage failed to alleviate inflammatory symptoms, while mice receiving the cocktail twice a day for 15 days were protected from clinical and microscopic manifestations of inflammation. (Titecat, et al. J Crohns Colitis. 2022 Nov 1;16(10):1617-1627. doi: 10.1093/ecco-jcc/jjac064. PMID: 35997152; Results). However, AIEC (LF82SK) remained detectable in the treated mice (Tables 2A and 2B). Notably, ECML-123-2 was one of the phage provided in the cocktail (Table 1).
Additionally, it is known in the art that immunogenicity doesn’t necessarily predict protective efficacy in bacterial vaccines. For example, commercially available MAP vaccines generally consist of live attenuated or killed whole bacteria with a mineral oil adjuvant. These vaccines reduce the clinical signs and shedding of MAP, but do not prevent all animals from infection and subsequent transmission of the bacteria. Subunit vaccines generally have not provided the desired level of protection against MAP. See Lybeck, et al. (Front. Immunol. 15:1297955, 20 pages) at p.2, left and right columns.
Thus, the state of the art recognized that it would be highly unpredictable that an AIEC lytic phage, or merely an AIEC cell lysate, could prevent AIEC infection or colonization. One of skill in the art would neither expect nor predict the appropriate functioning of the phage.
In view of the lack of the predictability of the art to which the invention pertains as evidenced by Titecat and Lybeck, the lack of guidance and direction provided by applicants, and the absence of working examples, undue experimentation would be required to vaccine a subject against AIEC infection, comprising administering to the subject a bacterial lysate obtained by lysing an AIEC strain with an isolated bacteriophage of strain ECML-123-2 deposited with the ATCC under Accession Number PTA-121408 with a reasonable expectation of success, absent a specific and detailed description in applicant’s specification of how to effectively practice this and absent working examples providing evidence which is reasonably predictive that the claimed method is functional, commensurate in scope with the claimed invention.
Enablement - Deposit
Claims 1, 9, and 24-26 are rejected under 35 U.S.C. § 112 (pre-AIA ), first paragraph or 35 U.S.C. 112(a), because 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, because the specification does not provide evidence that the claimed biological materials are (1) known and readily available to the public; (2) reproducible from the written description.
It is unclear if the bacteriophage strain ECML-123-2 (or a variant strain thereof with at least 80% average nucleotide identity across its genome) is known and publicly available, or can be reproducibly isolated without undue experimentation. Therefore, a suitable deposit for patent purposes is suggested. Without a publicly available deposit of the above bacteriophage, one of ordinary skill in the art could not be assured of the ability to practice the invention as claimed. Exact replication of the claimed bacteriophage strain ECML-123-2 is an unpredictable event.
If the deposit is made under the provisions of the Budapest Treaty, filing of an affidavit or declaration by applicant or assignees or a statement by an attorney of record who has authority and control over the conditions of deposit over his or her signature and registration number stating that the deposit has been accepted by an International Depository Authority under the provisions of the Budapest Treaty and that all restrictions upon public access to the deposited material will be irrevocably removed upon the grant of a patent on this application. 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 is not made under the provisions of the Budapest Treaty, then in order to certify that the deposits comply with the criteria set forth in 37 CFR 1.801-1.809 regarding availability and permanency of deposits, assurance of compliance is required. Such assurance may be in the form of an affidavit or declaration by applicants or assignees or in the form of a statement by an attorney of record who has the authority and control over the conditions of deposit over his or her signature and registration number averring:
(a) during the pendency of this application, access to the deposits will be afforded to the Commissioner upon request:
(b) all restrictions upon the availability to the public of the deposited biological material will be irrevocably removed upon the granting of a patent on this application:
(c) the deposits will be maintained in a public depository for a period of at least thirty years from the date of deposit or for the enforceable life of the patent of or for a period of five years after the date of the most recent request for the furnishing of a sample of the deposited biological material, whichever is longest; and
(d) the deposits will be replaced if they should become nonviable or non-replicable.
In the instant case, the specification states Phage P2 and CLBP2 were deposited under the terms of the Budapest Treaty, but makes no mention of Phage ECML-123-2 being deposited, instead saying “Phage ECLM-123-2 was deposited with the American Type Culture Collection under PTA 121408 on July 25, 2014. It is not clear that the deposit was made under the terms of the Budapest Treaty, nor is there available a viability statement, i.e. one certifying that the deposit was viable at the time of the deposit or a certificate verifying such from the depository.
Amendment of the specification to recite the date of deposit and the complete name and address of the depository is required. As an additional means for completing the record, applicant may submit a copy of the contract with the depository for deposit and maintenance of each deposit.
If a deposit is 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 biological material described in the specification as filed is the same as that deposited in the depository, stating that the deposited material is identical to the biological material described in the specification and was 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.
Written Description
Claims 1, 9, and 24-26 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 above are drawn to a method of treating inflammatory bowel disease (IBD) in a subject in need thereof, comprising administering to the subject a bacteriophage composition comprising a bacteriophage strain capable of producing a lytic infection in an adherent-invasive Escherichia coli strain, and a pharmaceutically acceptable carrier, wherein the bacteriophage strain is strain ECML-123-2 deposited with the ATCC under Accession Number PTA-121408, or a variant strain thereof, wherein the variant strain has at least 80% average nucleotide identity across its genome (gANI) to said bacteriophage strain ECML-123-2.
Even if the prior art is aware of such mutated bacteriophage that are capable of producing a lytic infection in an AIEC strain, the totality of known bacteriophage would not be representative of the entire genus for the reasons discussed below.
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
An applicant may show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics. Enzo Biochem, 323 F.3d at 964, 63 USPQ2d at 1613.
Furthermore, to satisfy the written description requirement for the genus of a bacteriophage strain capable of producing a lytic infection in an adherent-invasive Escherichia coli strain, and a pharmaceutically acceptable carrier, wherein the bacteriophage strain is strain ECML-123-2 deposited with the ATCC under Accession Number PTA-121408, or a variant strain thereof, wherein the variant strain has at least 80% average nucleotide identity across its genome (gANI) to said bacteriophage strain ECML-123-2, Applicant must adequately describe representative bacteriophage to reflect the structural diversity of the claimed genus. See Eli Lilly, 119 F.3d at 1568 (“[N]aming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material.”); Fiers v. Revel, 984 F.2d 1164, 1171 (Fed. Cir. 1993) (“Claiming all DNA[s] that achieve a result without defining what means will do so is not in compliance with the description requirement; it is an attempt to preempt the future before it has arrived.”).
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. A “representative number of species” means that the species which are adequately described are representative of the entire genus. See, e.g., AbbVie Deutschland GMBH v. Janssen Biotech, 759 F.3d 1285, 111 USPQ2d 1780 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, as here in which the bacteriophage claimed can have sequence variation, one must describe a sufficient variety of species to reflect the variation within the genus. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615. “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.” One of skill in this art cannot envision the structure of every bacteriophage strain capable of producing a lytic infection in an adherent-invasive Escherichia coli strain, and a pharmaceutically acceptable carrier, wherein the bacteriophage strain is strain ECML-123-2 deposited with the ATCC under Accession Number PTA-121408, or a variant strain thereof, wherein the variant strain has at least 80% average nucleotide identity across its genome (gANI) to said bacteriophage strain ECML-123-2. The specification does not describe any variants of bacteriophage strain ECML-123-2 or demonstrate their ability to lyse AIEC or treat IBD. Therefore, since no species are provided to represent these genera, the claims encompassing the same clearly fail the written description requirement.
Functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. See ABBVIE DEUTSCHLAND GMBH & 2 CO. v. JANSSEN BIOTECH, INC., Appeals from the United States District Court for the District of Massachusetts in Nos. 09-CV-11340-FDS, 10-CV-40003-FDS, and 10-CV-40004-FDS, Judge F. Dennis Saylor, IV. See also Ariad, 598 F.3d at 1351 (“[T]he level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology.”); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1352 (Fed. Cir. 2011) (noting the technical challenges in developing fully human antibodies of a known human protein).
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). The recitation of a functional property alone, which must be shared by the members of the genus, is merely descriptive of what the members of the genus must be capable of doing, not of the substance and structure of the members.
“Functional” terminology may be used “when the art has established a correlation between structure and function” but “merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing one has invented a genus and not just a species.” Ariad Pharmaceuticals Inc. v. Eli Lilly & Co., 598 F3d 1336, 94 USPQ2d 1161, 1171 (Fed Cir. 2010).
Even when several species are disclosed, these are not necessarily representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (“The ’128 and ’485 patents, however, only describe species of structurally similar antibodies that were derived from Joe-9. Although the number of the described species appears high quantitatively, the described species are all of the similar type and do not qualitatively represent other types of antibodies encompassed by the genus.”). Thus, when there is substantial variation within the genus, as here, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. Since each genus recited in the instant claims is large, it would be very challenging to describe sufficient species to cover the structures of the entire genus. Zero representative species of ECML-123-2 variants capable of lysing AIEC or treating IBD is certainly not adequate. The disclosure does not provide examples of other mutants or truncations that confer the required function.
Overall, at the time the invention was made, the level of skill for preparing bacteriophage was high.
A representative number of species has not been taught to describe these genera; one of skill in the art would conclude that applicant was not in possession of the structural attributes of a representative number of species possessed by the members of the genera bacteriophage capable of lysing AIEC. One of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genera.
The genus is large and would encompass structures that cannot be visualized from the prior art or instant disclosure. One of skill in this art cannot determine the structures encompassed by the claimed genera only defined by function. Any future ECML-123-2 derived bacteriophage may or may not be encompassed, and if it is, it would not have been represented in Applicant’s disclosed species. Thus, the described species cannot be considered representative of the recited genera of bacteriophage in the claimed method. E.g., AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). Thus, the claims are rejected here.
As discussed above, an applicant may show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics. Enzo Biochem, 323 F.3d at 964, 63 USPQ2d at 1613. Therefore, it is recommended that the instant claims be amended to recite complete structural information of the claimed bacteriophage, including full sequences.
Claim Rejections – Improper Markush Grouping
Claims 1, 9, and 24-26 are rejected on the judicially-created basis that they contain an improper Markush grouping of alternatives.
See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984).
The improper Markush grouping includes species of the claimed invention that do not share both a substantial structural feature and a common use that flows from the substantial structural feature. The members of the improper Markush grouping do not share a substantial structural feature and a common use that flows from the substantial structural feature for the following reasons:
MPEP 803.02 provides guidance on the analysis of a proper Markush group. Members of a proper Markush group are disclosed in the specification to possess at least one property in common which is mainly responsible for their function in the claimed relationship, and it is clear from their very nature or from the prior art that all of them possess this property. The MPEP further provides that in the members of a proper Markush group there should be (1) a common utility, and (2) a substantial structural feature essential to that utility.
In the instant case, claims 1, 9, and 24-26 include the group of diseases: inflammatory bowel disease (IBD), urinary tract infection (UTI), neonatal meningitis, asthma, chronic obstructive pulmonary disease (COPD), bronchitis, pneumonia, lung cancer, or modulating a human subject’s microbiome, but they do not appear to share a substantial structural feature, which would be a common affected cell type. Thus, a common use cannot flow from a shared substantial structural feature in these claims. Since the instant claims contain Markush groups with members of diseases that do not affect a common cell type of the disease, the claims contain an improper Markush group and are rejected here. For instance, the claimed diseases require different tissues, several are not related to AIEC colonization, and there is no common diseased cell type in all members of the Markush group of diseases, nor common cause. Asthma involves non-cancerous cells for example but lung cancer involves cancerous cells and thus at least these two species do not share a common affected cell type, for example. Additionally, not all of the diseases share a common structure that causes the disease.
In response to this rejection, Applicant should either amend the claim(s) to recite only individual species or grouping of species that share a substantial structural feature as well as a common use that flows from the substantial structural feature, or present a sufficient showing that the species recited in the alternative of the claims(s) in fact share a substantial structural feature as well as a common use that flows from the substantial structural feature. This is a rejection on the merits and may be appealed to the Board of Patent Appeals and Interferences in accordance with 35 U.S.C. §134 and 37 CFR 41.31(a)(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.
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.
Claim 41 is rejected under 35 U.S.C. 103 as being unpatentable over Nesta, et al. (Vaccines Against Escherichia coli. In: Frankel, G., Ron, E. (eds) Escherichia coli, a Versatile Pathogen. Current Topics in Microbiology and Immunology, vol 416. Springer, Cham., 2018).
The claimed invention encompasses a method for vaccinating a subject against AIEC infection, comprising administering to the subject a bacterial lysate obtained by lysing an AIEC strain with an isolated bacteriophage of strain ECML-123-2 deposited with ATCC under Accession Number PTA-121408 (represented by claim 41).
The Prior Art
Nesta discloses a number of different strategies to vaccinate against E. coli, including E. coli killed vaccines (Fig. 1; p. 216). Nesta elaborates that E. coli vaccines proposed today are based on live attenuated strains rationally designed to be safe, with deletions in genes important for virulence and with improved immunogenicity, overexpressing selected antigens, or on whole inactivated strains and/or on new promising vaccine antigens discovered by proteomic and genomic approaches (p. 216, last para.; Fig. 1). Additionally, Nesta teaches that vaccines based on whole or lysed fractions of inactivated E. coli have been evaluated in human trials, and have been the effective, for example in subjects undergoing recurrent urinary tract infections (pp. 217-218). Nesta also teaches that adherent-invasive E. coli (AIEC) is a major intestinal pathotype (p. 216, para. 1).
However, Nesta does not specifically disclose AIEC lysate or its use in a method of vaccination.
It would have been obvious to one of ordinary skill in the art to modify the method of vaccinating against E. coli using an E. coli lysate taught by Nesta to use adherent-invasive E. coli (AIEC) lysate to vaccinate against AIEC.
“[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in product -by- process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).
Notably, the “bacterial lysate obtained by lysing an AIEC strain with an isolated bacteriophage of strain ECML-123-2 deposited with the ATCC under Accession Number PTA-121408” of claim 41 is being interpreted as a product-by-process. Because the product administered is recited as a product by process, the analysis is the same as a product by process claim. If the prior art uses what appears to be a similar product, then even if it were made by a different process, it can still anticipate or render obvious the claimed invention.
One of ordinary skill in the art would have been motivated to vaccinate against AIEC, which Nesta teaches is a major intestinal pathotype.
There would have been a reasonable expectation of success because Nesta discloses vaccination with other, generic E. coli lysates.
Therefore, claim 41 would have been prima facie obvious to one of ordinary skill in the art before the priority date of the instant application.
Conclusion
No claim is allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEFFREY MARK SIFFORD whose telephone number is 571-272-7289. The examiner can normally be reached 8:30 a.m. - 5:30 p.m. ET with alternating Fridays off.
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/JEFFREY MARK SIFFORD/Examiner, Art Unit 1671 /Michael Allen/Supervisory Patent Examiner, Art Unit 1671
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