DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
This application claims priority to US application No. 18/491,099, filed October 20, 2023
and US application No. 17/326,561, filed May 21, 2021.
This application is a CON of 18/491,099, filed August 20, 2023; 18/491,099 is a CON of 17/326,561, filed May 21, 2021; 17/326,561 is a CON of 16/258,505, filed January 25, 2019; and
16/258,505 has PRO 62/622,722, filed January 26, 2018.
Status of Claims
Claims 1-18 were filed on August 26, 2024. Claims 1-18 are currently examined on the merits herein.
Information Disclosure Statement
Information disclosure statements (IDS) filed on August 26, 2024, under consideration by the Examiner.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.831(a) and 1.831(b). However, this application fails to comply with the requirements of 37 CFR 1.831-1.834.
In particular, each of the amino acid sequences at, e.g., pages 2-4, 10-11, 12, 13, 15-17, and 33, and claims 6, 12-14, and 18, comprises D-amino acids. However, the presence of D-amino acids is not indicated in the Sequence Listing filed August 26, 2024. See especially MPEP 2412.04(d)(III) and ST.26, paragraph 30 and paragraph 31, Example 3.
Required response – Applicant must provide:
• A replacement “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2., as well as
• A statement that identifies the location of all additions, deletions, or replacements of sequence information in the “Sequence Listing XML” as required by 1.835(b)(3);
• A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.835(b)(4); and
• A statement that the “Sequence Listing XML” includes no new matter in accordance with 1.835(b)(5)
Claim Objections
Claim 1 is objected to because of the following informalities: At line 2, “effective” should be deleted and should be re-inserted before “to treat”.
Claim 7 is objected to because of the following informalities: At line 2, “effective” should be deleted and should be re-inserted before “to limit”.
Claim 14 is objected to because of the following informalities: A SEQ ID NO must be inserted after the amino acid sequence set forth. See 37 CFR 1.821(d).
Claim 16 is objected to because of the following informalities: “peptide” should be changed to “peptides”.
Appropriate correction is required.
Sequence Interpretation
Regarding claims 6, 12-14, and 18, the scope of the peptides defined using “comprising” and “comprises” terminology, is being interpreted as open-ended, in which additional chemical moieties, e.g., amino acid residues, can be present and covalently attached to either terminus of the amino acid sequences.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 6, 7, 12-14, and 18 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claims 6, 12-14, and 18 recite sequences using both upper case and lower case letters. Further, SEQ ID NO:3 in claim 13, and the sequence in claim 14, use boldface cysteine residues. However, neither the claims nor the Sequence Listing filed on August 26, 2024, provide any indication or guidance as to how these format differences in the amino acid abbreviations are to be interpreted. Thus, the terminology used to recite the amino acid sequences in instant claims 6, 12-14, and 18 is unclear. The specification at page 9, lines 6-8, indicates that for the peptide sequences “disclosed herein”, lower case and underlined letters denote amino acids in a D-configuration. However, this section of the specification does not indicate how lower case but non-underlined letters are to be interpreted, and is silent as to the meaning of boldface letters. The specification at page 17, lines 4-6, apparently limited to the peptides recited in Table 2, indicates that lower case and underlined letters denote D-amino acids, and that disulfide-bonded cysteines in AP407 are shown in bold. Again, this section of the specification does not indicate how lower case but non-underlined letters are to be interpreted. In order to interpret the claim terminology, it might be necessary for Applicant to explicitly recite claim terminology definitions in each of the claims reciting a sequence.
Claim 7 recites, “comprising administering to a subject at risk of a bacterial infection comprising biofilm formation with an amount effective of an α-sheet peptide to limit development of the bacterial biofilm”. The language is indefinite because it is not clear, and it is unclear what the phrase is referring to. According to the claim, it does not require the subject to actually be infected by the bacteria, and the instant specification does not specify the degree of risk or the time period over which the degree of risk must be calculated.
Further, by virtue of their dependency on claim 7, claim 8 is also rejected for the same reasoning.
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.
First Rejection – Written Description
Claims 1-18 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 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 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.
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 inventor was in possession of the claimed genus.
Scope of the claims
The claims are drawn to “the α-sheet peptide comprises a peptide selected from the group consisting of”. The rejection stems from the limitation “α-sheet peptide comprises,” which does not disclose peptides as currently recited in instant claims 6, 12-14, and 18, defined using “comprising” and “comprises” terminology, in which additional chemical moieties, e.g., amino acid residues, can be present and covalently attached to either terminus of the amino acid sequences; and does not disclose placing an α-sheet peptide on a medical device or on a surface of a medical device; and does not disclose combining an α-sheet peptide with a pharmaceutically acceptable carrier. There is nothing further in the claim to indicate the structural feature(s) (i.e., an amino acid sequence(s)) required to meet this functional limitation, and describing an invention by function is insufficient to meet the written description requirement.
Actual Reduction to Practice
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. A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
In the instant case, several embodiments of the invention were reduced to practice: see Polydopamine Coating for Conjugation of α-Sheet Peptides to Biomaterials, FIG. 17. The specification states that in another embodiment, the surgical procedure may comprise placement of a medical device in the subject. In a further embodiment, the medical device may include, but is not limited to, prosthetic heart valves, cardiac pacemakers, cerebrospinal fluid shunts, urinary catheters, intravascular catheters, ocular prostheses, and intrauterine contraceptive devices. In another embodiment, the α-sheet peptide may be placed on the medical device prior to placement of the medical device in the subject (see Summary, page 3, line 5-10). FIG. 17 shows Bacterial adherence and growth of biofilm on glass disks and decreased adhesion of bacteria (GFP signal) and biofilm and amyloid formation (Brightfield image) when glass is coated with α-sheet peptides, shown for dimeric AP193. This is a model for biofilm formation on implanted devices such as prosthetic joints (see page 8, line 11-15, FIG. 17). Although the variations are allowed by the claims, they are not represented in the reduction to practice. Thus, one cannot extrapolate how placing a α-sheet peptide on a medical device or on a surface of a medical device might impact its functionality.
Sufficient relevant identifying characteristic
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 thereof.
i. Complete structure:
As stated above, the complete structure of the peptides (see [0006]) are disclosed.
ii. Partial structure:
The specification states that In a further aspect, the disclosure provides medical devices comprising one or more α-sheet peptides coated on a surface of the medical device. In one embodiment, the medical devices may include, but are not limited to, prosthetic heart valves, cardiac pacemakers, cerebrospinal fluid shunts, urinary catheters, intravascular catheters, ocular prostheses, and intrauterine contraceptive devices. In another embodiment, the α-sheet peptide may comprise one or more peptides including, but not limited to:
AP90 ( SEQ ID NO: 1), AP401 (SEQ ID NO: 2), AP407 (SEQ ID NO: 3), AP193 (SEQ ID NO: 4), and AP5 (SEQ ID NO: 8) (see page 4, line 9-14). And as stated above, the recitation in instant claims 6, 12-14, and 18, defined using “comprising” and “comprises” terminology, in which additional chemical moieties, e.g., amino acid residues, can be present and covalently attached to either terminus of the amino acid sequences; and does not disclose placing an α-sheet peptide on a medical device or on a surface of a medical device; and does not disclose combining an α-sheet peptide with a pharmaceutically acceptable carrier. Therefore, it is unclear from the partial structure which additional elements are necessary to meet all of the claimed properties of the genus.
iii. Physical and/or chemical properties:
The data presented in the specification and examples raise more questions about the physical properties of the genus than they answer. The data does not suggest the physical basis for the α-sheet peptide derivatives and therefore do not describe which substitutions, deletions or additions could be made while preserving the structure. Understanding the physical basis for biofilm formation on the surface of the devices is critical to determining which of the sequences that meet the sequence requirements of the genus also meet this additional functional requirement of the genus.
iv. Functional characteristics when coupled with a known or disclosed correlation between function and structure:
The specification does not describe a general correlation between sequence and structural coordinates for the claimed genus. As a result, it is impossible to predict, based on the specification, how changing the derivatives or peptide bonding will affect the biofilm formation.
v. Method of making the claim invention:
Computational Peptide Design and Synthesis and the cloning, recombinant expression and purification of proteins is well-known in the art. It is not disputed that one of ordinary skill in the art could isolate, albeit with route experimentation and optimization, a polypeptide of a given sequence provided that the sequence is known. Where the specification fails to provide description is in the structure of the polypeptide derivative to make. For all of the reasons presented above, one of ordinary skill in the art would not know which of the countless peptides that meet the sequence and modification requirements of the claims would also have specific structural conformation with antimicrobial effect. Consequently, it is unknown whether all variants encompassed or polypeptide segments having the function of treating bacterial infection, and would retain the structural, chemical, and/or physical properties required to engage in the disruption of the biofilm to effectively enhance the treatment against hospital acquired bacterial infection.
Therefore, the instant specification does not provide adequate written description to possess the broad genus described above since the specification does not disclose a correlation between the necessary structure of the sequence and the claimed function to be maintained.
Conclusion
For these reasons, the skilled artisan would not reasonably conclude that the inventor(s), at the time the application was filed, had possession of the full scope of the claimed invention.
Second Rejection – Scope of Enablement
Claims 1, and 4-6 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the instantly claimed invention is enabled for treating bacterial infection caused by Escherichia coli, a Pseudomonas aeruginosa, or a Staphylococcus aureus, however, , does not reasonably provide enablement for treating all bacterial infection. 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 Applicant’s attention is drawn to In re Wands, 8 USPQ2d 1400 (CAFC1988) at 1404 where the court set forth eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors:
(1) The nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
The nature of the invention and the breadth of the claims
The claims are drawn to a method of treating a bacterial infection comprising administering to a subject with a bacterial infection an amount effective of an a-sheet peptide to treat the bacterial infection; wherein the bacterial infection comprises a drug or multi- drug-resistant bacterial infection; wherein the bacterial infection is contracted during hospitalization.
Embodiments of the instant specification disclose the bacterial infection may comprise a drug or multi-drug resistant bacterial infection (see [0005]); reducing the severity of the infection or extent of the biofilm; limiting or preventing development of symptoms characteristic of the infection or biofilm being treated; limiting or preventing recurrence of the infection or biofilm in patients that have previously had the infection or biofilm; limiting or preventing recurrence of symptoms in patients that were previously symptomatic for the infection or biofilm (see [0037]).
However, treating all bacterial infection as claimed reads on administering effective amount of an α -sheet peptide to any individual with a bacterial infection. The specification does not teach a method of treating all types of bacterial infection for a patient in need, using the therapeutic peptide as claimed. Accordingly, claim 1 and dependent claims are unduly broad with respect to a method of treating all bacterial infection.
The State of the Prior Art and The Level of Predictability in the Art
The state of the art at the time of filing did not recognize that an α -sheet peptide could prevent a range of bacterial infections or related diseases. For instance, while Applicants are enabled for treating a subset of bacterial infections (see instant [0036]) and prior art below, the art does not recognize that all bacterial infections can be prevented, let alone with designed inhibitory compound such as the instant α -sheet peptide. Although the instant specification states the method can be used to treat any suitable bacterial infection, including but not limited to any bacterial infection that may comprise biofilm formation (see [0036]), there is no prior art that teaches α -sheet peptide of claim 1 can treat all bacterial infections. Prior art has investigated therapeutics for treating some bacterial infections caused by formation of biofilms, that suggest that therapeutic treatment for all bacterial infections might be possible someday but is presently not an option.
The Level of Skill in the Art
Practitioners in this art (clinicians, scientists) would presumably be highly skilled in the art for prevention or treatment of disease in a subject.
The Amount of Direction Provided by the Inventor
At the time of filing, no direction or guidance was presented in either the prior art or the instant specification that would enable one to administer α -sheet peptide to treat a bacterial infection as claimed. The instant specification does not provide adequate guidance with regard to the actual treatment or the effective amount of the compound that is required to prevent any bacterial infection. Applicants’ limited disclosure is noted but is not sufficient to justify claiming treatment of all bacterial infections in a subject broadly. Absent a reasonable a priori expectation of success for using the α -sheet peptide as a method of treatment, one skilled in the art would have to extensively test the inhibitor compound on a representative number of subjects, determine dosing using different concentrations of the compound and ascertain a prevention standard.
The Presence or Absence of Working Examples
The instant specification provides no examples wherein α -sheet peptide is administered to any kind of bacterial infection or related disease.
The quantity of experimentation necessary
As there are no working examples in either the instant specification nor the prior art, reasonable guidance with respect to treating a bacterial infection through administration of a α -sheet peptide was limited. Consequently, one skilled in the art would be burdened with undue experimentation to determine the precise parameters and conditions necessary to effectively treat a bacterial infection.
Therefore, in view of the Wands factors, as discussed above, Applicants fail to provide sufficient information to practice the claimed invention for the treatment of a bacterial infection.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 7 and 12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by U.S. Patent Application Publication 2016/0031952, hereafter US’952, (published February 4, 2016, cited in IDS filed on August 26, 2024).
US’952 teaches peptide corresponding to the instantly claimed SEQ ID NO:4. US’952 also teach their peptides in combination with a pharmaceutically acceptable carrier (see Figure 5, Peptide #10, also identified as SEQ ID NO:150; and paragraphs [0245] and [0247]).
For claims 7 and 12: US’952 teaches the polypeptides adopt an α-sheet structure, regardless of the primary amino acid sequence and thus can be used, for example, in the therapeutic and diagnostic methods; the polypeptides of the invention are useful for inhibiting aggregation and/or binding of the toxic oligomeric form of amyloidogenic intermediates (see [0052]). US’952 emphasizes the ability of the polypeptides to adopt a stable α-sheet structure that is operative here, and that is achieved through the recited polypeptide generic structure and the recited arrangement of alternating D/L amino acids (see [0052]). In another embodiment, the polypeptide comprises or consists of a primary amino acid sequence selected from the group consisting of the following polypeptides or their reverse chiral counterparts (see [0244]). US’952 provides methods for treating an amyloid disease, comprising administering to a subject with an amyloid disease an amount effective of the isolated polypeptide of any embodiment or combination of embodiments of the invention, or a pharmaceutical composition thereof, to treat the amyloid disease (see [0255]) and an “amount effective” refers to an amount of the polypeptide that is effective for treating (see [0258]).
Examiner’s Note: Claim 7 recites “a subject at risk of developing a bacterial infection comprising biofilm formation”, and that reasonably all patients can be considered to be at risk.
Accordingly, because US’952 teach administering the same alpha-sheet peptides to the same subjects according to the same method steps as are instantly claimed, inherently bacterial biofilm development will be limited, e.g. prevented, in the treatment method of US’952 to the same extent as instantly claimed.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-18 are rejected under 35 U.S.C. 103 as being unpatentable over Bleem et. al. (“Designed α-sheet peptides suppress amyloid formation in Staphylococcus aureus biofilms”; Alissa Bleem, Robyn Francisco, James D. Bryers and Valerie Daggett; npj Biofilms and Microbiomes (2017) 3:16; including the Supplementary Information; published July 3, 2017; cited in IDS filed on August 26, 2024).
Bleem et. al. teaches Methicillin-resistant Staphylococcus aureus (MRSA), in particular,
is a major cause of nosocomial infections due to its versatility and arsenal of virulence factors. Bleem et. al. further teaches that when Staphylococcus aureus forms a biofilm on a medical device or wound, cells associate with surfaces and each other using a self-produced extracellular matrix (EM) composed of proteins, polysaccharides, and genetic material (see page 1, right col, paragraph 2). Bleem et. al. demonstrates the assembly of a bacterial amyloid is inhibited by the designed α-sheet peptides (see page 8, left col, paragraph 2).
Regarding claims 1 and 2: Bleem et. al. show that these anti-α-sheet peptides inhibit amyloid formation in Staphylococcus aureus biofilms (see Abstract). Bleem et. al. discloses the α-sheet peptide designs inhibit amyloid formation in both systems and ultimately compromise the integrity of the S. aureus biofilms (see page 2, left col, paragraph 2). Bleem et. al. discloses there was significant disruption of the biofilm in the presence of the α-sheet compound (see page 3, left col, paragraph 1). Bleem et. al. demonstrated suppression amyloidogenesis in the S. aureus biofilm matrix through the use of de novo α-sheet peptides (see page 6, left col, paragraph 3).
Regarding claim 3: Bleem et. al. teaches α-sheet inhibitors could prove applicable to a wide variety of amyloidogenic proteins, including functional amyloids produced by other
bacterial species such as Escherichia coli and Pseudomonas aeruginosa (see page 2, left col, paragraph 2).
Regarding claim 4: Bleem et. al. teaches an increasing number of infectious biofilms are
formed by multidrug resistant bacteria (see page 1, left col, paragraph 1).
Regarding claim 5: Bleem et. al. teaches patients contracted at least one infection during the course of hospitalization (see page 1, left col, paragraph 1); and soluble modulins and small amounts of soluble modulins α3 have been detected in different community-acquired and hospital-acquired MRSA strains (see page 7, right col, paragraph 1).
Regarding claims 6, 12-15 and 18: Bleem et. al. teaches alpha-sheet peptides identical to the instantly claimed alpha sheet peptides identified as SEQ ID NOs:1-4 (see Table S1 of the Supplementary Information). The alpha-sheet peptide AP407 taught by the Bleem et. al. also comprises disulfide-linked cysteine residues. The peptides of the Bleem et. al. are dissolved in phosphate or acetate buffer (see Figure S1 of the Supplementary Information), for which buffers correspond to the pharmaceutically acceptable carrier of instant claim 15.
Regarding claims 7-10, and 17: Bleem et. al. teaches microbial infections occur within surgical wounds, as well as on nearly all implanted medical devices, including prosthetic heart valves, pacemakers, cerebrospinal fluid shunts, urinary and intravascular catheters, ocular prostheses, and intrauterine contraceptive devices (see page 1, left col, paragraph 1). Bleem et. al. teaches the prevalence of soluble modulins in drug-resistant infections, combined with their ability to influence biofilm development, has made them an attractive target for therapeutic intervention in recent years. Bleem et. al. demonstrated a novel approach to suppress amyloidogenesis in the S. aureus biofilm matrix through the use of de novo α-sheet peptides (see page 6, left col, paragraph 3), and the α-sheet peptide designs inhibit amyloid formation in
both systems and ultimately compromise the integrity of the S. aureus biofilms (see page 2, left col, paragraph 2).
Based on the study, Bleem et. al. proposes that investigating the potential therapeutic
effects of α-sheet compounds for next generation peptide designs to reduce the amyloid content of the biofilm matrix (see page 8, left col, paragraph 1), in treating medical device and hospital acquired bacterial infection, may promote the design of therapeutic strategies and help improve the treatment and outcomes of patients suffering from serious bacterial infections.
Therefore, before the effective filing date of the claimed invention, the claimed invention was prima facie obvious to the artisan of the ordinary skill. It would have been prima facie obvious for one of ordinary skill in the art to enhance the teachings of Bleem et. al. with the expectation to achieve therapeutic agents suitable for treating bacterial infection.
Regarding claims 11 and 16: Bleem et. al. designed α-sheet peptides inhibit amyloid formation in biofilm cultures (see page 2, right col, paragraph 2-3); and designed peptide inhibitors disrupt S. aureus biofilms (see page 2, right col, paragraph 4, page 3, left col, paragraph 1). Bleem et. al. studied the ability of designed peptides to inhibit amyloid formation, S. aureus MN8 biofilms were grown in culture plates with glass bottom wells with or without α-sheet inhibitors; observed a robust biofilm formed on the glass at the bottom of each well in contrast, there was significant disruption of the biofilm in the presence of the α-sheet compounds. AP407, for example, caused nearly all of the biofilm to detach from the slide upon rinsing (see page 2-3, left col, paragraph 1, Fig 2a). Bleem et. al. demonstrates S. aureus biofilm structures become less robust when grown in the presence of designed peptide inhibitors. Like S. aureus biofilms were grown on glass substrates for 24 h and then cells were washed and fixed, the peptide inhibitors caused cells to detach during the wash step (see Fig 2), and also show designed peptides reduce the number of cells attached to glass slides after washing (see Fig. S2). Bleem et. al. specifies there was significant disruption of the biofilm in the presence of the α-sheet compounds; AP407, for example, caused nearly all of the biofilm to detach from the slide upon rinsing (see page 3, left col, paragraph 1, Fig. S2).
Based on the teachings of Bleem et. al. above, it would have been obvious to utilize the antimicrobial activity of designed peptides, more specifically α-sheet compounds could be administered as therapeutic agents for biofilm-associated bacterial infection. It would have been obvious to inhibit bacterial biofilms as disclosed by Bleem et. al., i.e., preferably peptide designs to reduce the amyloid content of the biofilm matrix (see page 8, left col, paragraph 1).
Therefore, before the effective filing date of the claimed invention, the claimed invention was prima facie obvious to the artisan of the ordinary skill. It would have been prima facie obvious for one of ordinary skill in the art to modify the teachings of Bleem et. al. with the expectation to achieve therapeutic agents suitable for treating bacterial infection associated with formation of biofilms in medical devices.
Double Patenting
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claims 1-6, 9-11, and 16-18 are rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 1-6, 8-10, and 12-14 of prior U.S. Patent No. 11,033,604, hereafter US’604 (published June 15, 2021, cited in IDS filed on August 26, 2024). This is a statutory double patenting rejection.
US’604 recites a method for treating a bacterial infection, comprising administering to a subject with a bacterial infection an amount of an α-sheet peptide effective to treat the bacterial infection (see claim 1); wherein the bacterial infection comprises a bacterial biofilm, and wherein the treating comprises disruption of the biofilm (see claim 2); wherein the bacterial infection comprises an Escherichia coli, a Pseudomonas aeruginosa, or a Staphylococcus aureus bacterial infection (see claim 3); wherein the bacterial infection comprises a drug or multi-drug resistant bacterial infection (see claim 4); wherein the bacterial infection is contracted during hospitalization (see claim 5); wherein the a-sheet peptide comprises a peptide selected from the group consisting of:
AP90 SEQ ID NO: 1 RGEmNlSwMNEYSGWtMnLkMGR;
AP401 SEQ ID NO: 2 rGeMnLsWmneysGwTmNlKmGr;
AP407 SEQ ID NO: 3 RGEmNlCwMNEYSGWcMnLkMGR;
AP193 SEQ ID NO: 4 RGEmNyFwMNEYYGWtMnCkMGR; and
AP5 SEQ ID NO: 8 RGNwNeSkMNEYSGWmLmLtMGR;
(see claim 6). Therefore, US‘604 anticipates instant claims 1-6.
For claim 9: US’604 claim 8 recites the surgical procedure comprises placement of a medical device in the subject.
For claim 10: US’604 claim 9 recites the medical device is selected from the group consisting of prosthetic heart valves, cardiac pacemakers, cerebrospinal fluid shunts, urinary catheters, intravascular catheters, ocular prostheses, prosthetic joints, orthopedic implants, titanium-containing implants, polystyrene-containing implants, and intrauterine contraceptive devices.
For claim 11: US’604 claim 10 recites the a-sheet peptide is placed on the medical device prior to placement of the medical device in the subject.
For claim 16: US’604 claim 12 recites a medical device comprising one or more a-sheet peptides coated on a surface of the medical device.
For claim 17: US’604 claim 13 recites the medical device is selected from the group consisting of prosthetic heart valves, cardiac pacemakers, cerebrospinal fluid shunts, urinary catheters, intravascular catheters, ocular prostheses, ….. and intrauterine contraceptive devices.
For claim 18: US’604 claim 14 recites the a-sheet peptide comprises a peptide selected from the group consisting of:
AP90 (SEQ ID NO: 1) RGEmNlSwMNEYSGWtMnLkMGR;
AP401 (SEQ ID NO: 2) rGeMnLsWmneysGwTmNlKmGr;
AP407 (SEQ ID NO: 3) RGEmNlCwMNEYSGWcMnLkMGR;
AP193 (SEQ ID NO: 4) RGEmNyFwMNEYYGWtMnCkMGR; and
AP5 (SEQ ID NO: 8) RGNwNeSkMNEYSGWmLmLtMGR
wherein residues in lower-case are D amino acids, residues in upper case are L amino acids, and G residues are achiral. [Note: which is in direct correlation with the instantly claimed invention as it specifies “In the various peptides sequences disclosed herein, lower case and underlined letters denote D-amino acids, while upper case letters represent L amino acids, while “G” is achiral (see [ 0033])”].
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 7, 8 and 12-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 7 and 11 of U.S. Patent No. 11,033,604 hereafter US’604 (published June 15, 2021, cited in IDS filed on August 26, 2024). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the US‘604 patent clearly anticipate the instant claims.
Note that claims to a species anticipate claims drawn to a genus.
Regarding claims 7 and 8: US’604 claim 7 recites a method for limiting development of bacterial biofilm, comprising administering to a subject at risk of a bacterial infection comprising biofilm formation with an amount of an α-sheet peptide effective to limit development of the bacterial biofilm, wherein the subject is undergoing a surgical procedure.
Regarding claims 12-15: US’604 claim 11 recites the α-sheet peptide comprises a peptide selected from the group consisting of:
AP90 SEQ ID NO: 1 RGEmNlSwMNEYSGWtMnLkMGR;
AP401 SEQ ID NO: 2 rGeMnLsWmneysGwTmNlKmGr;
AP407 SEQ ID NO: 3 RGEmNlCwMNEYSGWcMnLkMGR;
AP193 SEQ ID NO: 4 RGEmNyFwMNEYYGWtMnCkMGR; and
AP5 SEQ ID NO: 8 RGNwNeSkMNEYSGWmLmLtMGR
wherein residues in lower-case are D amino acids, residues in upper case are L amino acids and G residues are achiral. [Note: which is in direct correlation with the instantly claimed invention as it specifies “In the various peptides sequences disclosed herein, lower case and underlined letters denote D-amino acids, while upper case letters represent L amino acids, while “G” is achiral (see [ 0033])”].
Claims 1-18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 11,826,398 hereafter US’398 (published November 28, 2023, cited in IDS filed on August 26, 2024). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the US‘398 patent clearly anticipate the instant claims.
Note that claims to a species anticipate claims drawn to a genus. Further, the instant claims do not exclude the presence of an N-terminal acetyl group or a C-terminal amide group from the recited peptides.
Regarding claims 1-14 and 18: US’398 claim 1 recites a peptide consisting of the amino acid sequence selected from the group consisting of:
Ac-rGeMnLsWmneysGwTmNlKmGr-NH2 (SEQ ID NO:2);andAc-RGEmNlCwMNEYSGWcMnLkMGR-NH2 (SEQ ID NO:3);
wherein residues in lower-case are D amino acids, residues in upper case are L amino acids, and G residues are achiral. US’398 specification states in a further embodiment, the α-sheet peptide comprises one or more peptides including, but not limited to:
SEQ ID NO:1 AP90 RGEmNlSwMNEYSGWtMnLkMGR;
SEQ ID NO:2 AP401 rGeMnLsWmneysGwTmNlKmGr;
SEQ ID NO:3 AP407 RGEmNlCwMNEYSGWcMnLkMGR;
SEQ ID NO:4 AP193 RGEmNyFwMNEYYGWtMnCkMGR; and
SEQ ID NO:8 AP5 RGNwNeSkMNEYSGWmLmLtMGR (see SUMMARY, col 2, line 25-35).
US’398 claim 4 recites a method for treating a bacterial infection, comprising administering to a subject with a bacterial infection an amount of the peptide of claim 1 effective to treat the bacterial infection. Therefore, US‘398 claims anticipate instant claim 1, 6, 12-14, and 18.
US’398 claim 5 recites the bacterial infection comprises a bacterial biofilm, and wherein the treating comprises disruption of the biofilm. Therefore, US‘398 claims anticipate instant claim 2.
US’398 claim 6 recites the bacterial infection comprises an Escherichia coli, a Pseudomonas aeruginosa, or a Staphylococcus aureus bacterial infection. Therefore, US‘398 claims anticipate instant claim 3.
US’398 claim 7 recites the bacterial infection comprises a drug or multi-drug resistant bacterial infection. Therefore, US‘398 claims anticipate instant claim 4.
US’398 claim 8 recites the bacterial infection is contracted during hospitalization. Therefore, US‘398 claims anticipate instant claim 5.
US’398 claim 9 recites a method for limiting development of bacterial biofilm, comprising administering to a subject at risk of a bacterial infection comprising biofilm formation with an amount of the peptide of claim 1 effective to limit development of the bacterial biofilm, wherein the subject is undergoing a surgical procedure. Therefore, US‘398 claims anticipate instant claims 7 and 8.
US’398 claim 10 recites the surgical procedure comprises placement of a medical device in the subject. Therefore, US‘398 claims anticipate instant claim 9.
US’398 claim 11 recites the medical device is selected from the group consisting of prosthetic heart valves, cardiac pacemakers, cerebrospinal fluid shunts, urinary catheters, intravascular catheters, ocular prostheses, and intrauterine contraceptive devices. Therefore, US‘398 claims anticipate instant claim 10.
US’398 claim 12 recites the peptide is placed on the medical device prior to placement of the medical device in the subject. Therefore, US‘398 claims anticipate instant claim 11.
Regarding claim 16: US’398 claim 2 recites a medical device comprising the peptide of claim 1 coated on a surface of the medical device.
Regarding claim 17: US’398 claim 3 recites the medical device is selected from the group consisting of prosthetic heart valves, cardiac pacemakers, cerebrospinal fluid shunts, urinary catheters, intravascular catheters, ocular prostheses, and intrauterine contraceptive devices.
Conclusion
No claim is allowed.
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/KOYELI BANERJEE/ Examiner, Art Unit 1658
/Melissa L Fisher/ Supervisory Patent Examiner, Art Unit 1658
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