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 .
Application and Claims Status
Applicant’s preliminary amendments filed on October 24, 2025 are acknowledged and entered.
Claims 1, 2, 4-16, 19, 20, and 22-24 were pending. In the amendment as filed on October 24, 2025, applicants have amended claim 22; cancelled claims 1, 2, 4- 16, 19, 20, 23, and 24; and added new claims 25-42. Therefore, claims 22 and 25-42 are currently pending. Additionally, the present specification is amended in order to properly claim priority to related applications and to disclose government support.
Election/Restrictions
Applicant’s election of Group III, claim 22 in the reply filed on October 24, 2025 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)).
Information Disclosure Statement
The information disclosure statements (IDS) filed on 7/18/2023; 11/15/2024 are in compliance with the provisions of 37 CFR 1.97. All references have been considered except where marked with a strikethrough. A signed copy of Form 1449 is included with this Office Action.
Priority
The instant application is a §371 National State Application of PCT/US2022/014086 filed January 27, 2022, which claims priority from U.S. Provisional Application Serial No. 63/142,251 filed January 27, 2021.
Specification – Abstract
Applicant is reminded of the proper content of an abstract of the disclosure.
A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art.
If the patent is of a basic nature, the entire technical disclosure may be new in the art, and the abstract should be directed to the entire disclosure. If the patent is in the nature of an improvement in an old apparatus, process, product, or composition, the abstract should include the technical disclosure of the improvement. The abstract should also mention by way of example any preferred modifications or alternatives.
Where applicable, the abstract should include the following: (1) if a machine or apparatus, its organization and operation; (2) if an article, its method of making; (3) if a chemical compound, its identity and use; (4) if a mixture, its ingredients; (5) if a process, the steps.
Extensive mechanical and design details of an apparatus should not be included in the abstract. The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words in length.
See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts.
The abstract of the disclosure is objected to because: the abstract of the disclosure does not commence on a separate sheet in accordance with 37 CFR 1.52(b)(4) and 1.72(b). A new abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text.
Specification - Disclosure
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any of the errors of which applicant may become aware of in the specification.
Specification - Drawings
Acknowledgement is made of the drawings received July 18, 2023.
The drawings are objected to because:
in Fig. 5A, the luminescence/radiance scale and corresponding legend are not legible. One can not ascertain the units (ie, for radiance?) and power (ie. X104?, 5.00e6?) in the figure. As recited in 37 CFR 1.84:
(l) Character of lines, numbers, and letters. All drawings must be made by a process which will give them satisfactory reproduction characteristics. Every line, number, and letter must be durable, clean, black (except for color drawings), sufficiently dense and dark, and uniformly thick and well-defined. The weight of all lines and letters must be heavy enough to permit adequate reproduction. This requirement applies to all lines however fine, to shading, and to lines representing cut surfaces in sectional views. Lines and strokes of different thicknesses may be used in the same drawing where different thicknesses have a different meaning.
the sheet number and view are not oriented in the same direction. In Fig. 3B, the header and footer are not oriented in the correct landscape position as the rest of the figure. As recited in 37 CFR 1.84:
(p) Numbers, letters, and reference characters.
(1) Reference characters (numerals are preferred), sheet numbers, and view numbers must be plain and legible, and must not be used in association with brackets or inverted commas, or enclosed within outlines, e.g., encircled. They must be oriented in the same direction as the view so as to avoid having to rotate the sheet. Reference characters should be arranged to follow the profile of the object depicted.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claim 28 is objected to because of the following informalities: in the limitation of R7, applicant writes “R7 is H, hydroxyl…” and subscripts text beyond the “7”. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 22, 25-42 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 22 is rejected as vague. As it is currently written, it is unclear if both the coproporphyrinogen oxidase (CgoX) activator and the photosensitizer are conjugated to a targeting moiety, or if only the photosensitizer is conjugated to a targeting moiety. As claims 25-42 depend upon claim 22 and do not resolve the issue, they are also rejected.
Claim 28 is rejected to in its definition of the limitation for R8. It is unclear why a definition for a variable R8 appears in the text of the claims, yet no such variable appears among the diagrammed compounds. As claim 29 depends upon claim 28 and does not include a diagrammed compound with an R8 variable or do not provide compound species that define that position, it is also rejected.
Claims 28-30 are rejected for its use of improper Markush claim language. Markush claims are commonly formatted as “selected from the group consisting of A, B, and C” or “wherein R is A, B, C, or D.” In Claim 29, as an example, applicant recites “wherein R1 is H, alkyl, aryl; R2 is H, halogen, alkyl, aryl, heteroaryl…” and the claim is implied to be connected by “and”. The claim example should properly read, “wherein R1 is H, alkyl, or aryl; R2 is H, halogen, alkyl, aryl, or heteroaryl…”
Claim 28 and claims dependent thereon are rejected because the term “substituted” is indefinite. Claim 28 recites “…ring comprising C, O, S, and/or N optionally substituted with one or more R3”. In the absence of the specific moieties intended to effectuate modification by the “substitution” or attachment to the chemical core claimed, the term “substituted” renders the claims in which it appears indefinite in all occurrences wherein applicants fails to articulate by chemical name, structural formula or sufficiently distinct functional language, the particular moieties applicants regards as those which will facilitate substitution, requisite to identifying the composition of matter claimed. The specification provides a non-limiting definition (page 15, para 0067) with “the term ‘substituted’ is contemplated to include all permissible substituents of organic compounds.” Examiner suggests amending the claim to recite specific substituents which are supported by the specification.
Claim 28 and claims dependent thereon are rejected because the terms “alkyl”, “aryl”, “heteroaryl”, “amino”, “acetamide”, and “amino sulfonyl” are indefinite. The specification defines these terms (page 16-18, para 0069-0075) with the term “substituted”. For example, on page 16, para 0069, in the definition of “alkyl”, applicant writes, “the alkyl group can also be substituted or unsubstituted.” As discussed in the previous claim rejection, the term “substituted” is indefinite in all occurrences, thereby making all term definitions that embrace the term “substituted” also indefinite. Examiner suggests amending the claims to recite specific substitutions which are supported by the specification.
Claim Rejections – 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Scope of Enablement - Prevention
Claims 22, and 25-42 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AlA), first paragraph, because the specification, while being enabling for treatment, does not reasonably provide enablement for prevention. 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 following Wands factors have been considered if not explicitly discussed: (A) The breadth of the claims, (B) The nature of the invention, (C) The state of the prior art, (D) The level of one of ordinary skill, (E) The level of predictability in the art, (F) The amount of direction provided by the inventor, (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The term “treatment” is defined on page 18, para 0076 of the specification and said definition also embraces prevention.
It is presumed “prevention” of the claimed condition would require a method of identifying those individuals or animals who will develop the claimed condition before they exhibit symptoms. The current state of the art is that that full scope of diseases claimed within instant claims is not preventable or curable.
The factors to be considered in making an enablement rejection were summarized above. 1) Preventing diseases requires identifying those patients who will acquire the condition before the symptoms occur. This would require extensive and potentially open-ended clinical research on healthy subjects. 2) There is no working example of such a preventive procedure in man or animal in the specification. 4) The claims rejected are drawn to clinical pharmacology and are therefore physiological in nature. 5) The state of the art is that no general procedure is art-recognized for determining which patients generally will develop a skin or soft tissue infection before the fact. 6) The artisan using Applicants invention would be a Board Certified physician. Despite intensive efforts, pharmaceutical science has been unable to find a way of getting a compound to be effective for the prevention of a skin or soft tissue infection. Under such circumstances, it is proper for the PTO to require evidence that such an unprecedented feat has actually been accomplished, In re Ferens, 163 USPQ 609. No such evidence has been presented in this case. The failure of skilled scientists to achieve a goal is substantial evidence that achieving such a goal is beyond the skill of practitioners in that art, Genentech vs. Novo Nordisk, 42 USPQ2nd 1001, 1006. This establishes that it is not reasonable for any agent to be able to prevent a skin or soft tissue infection. 7) It is well established that "the scope of enablement varies inversely with the degree of unpredictability of the factors involved" and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). 8) The claims broadly read on all patients, not just those undergoing therapy for the claimed conditions.
As claims 25-42 depend upon claim 22, they are also rejected.
Scope of Enablement – Skin or Soft Tissue Infection
Claims 22 and 25-42 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 the treatment of skin of soft tissue infections (SSTI) caused by Gram-positive bacteria, does not reasonably provide enablement for the treatment of all SSTIs (such as those caused by Gram-negative bacteria, viral infections, fungal infections, etc). 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.
Such a utility cannot be deemed enabled. Pursuant to In re Wands, 858 F.2d 731,737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. Some experimentation is not fatal; the issue is whether the amount of experimentation is "undue"; see In re Vaeck, 20 USPQ2d 1438, 1444. The analysis is as follows:
Breadth of claims:
Scope of the compounds. The instant claims encompass tens of thousands of compounds with a benzo-pyrazole scaffold with a variety of substituents in a composition with a photosensitizer conjugated to a targeting moiety that selectively binds iron-regulated surface determinant (Isd) proteins.
Scope of the diseases covered. The instant claims are drawn to a method of treating SSTIs caused from any microbe. The treatment of any microbial (specifically, bacterial) infection generally cannot possibly be considered enabled. The source of bacterial infection is diverse and there is a large number of bacterial infections. Bacteria are single-celled microorganisms known as prokaryotes. There are estimated to be at least one nonillion bacteria on Earth. A nonillion is a one followed by 30 zeros. Much of Earth's biomass is made up of bacteria. Bacteria take three main shapes:
Spherical: These are usually the simplest to treat and are known as cocci.
Rod-shaped: These are called bacilli.
Spiral: Coiled bacteria are known as spirilla. If the coil of a spirillus is particularly tight, they are known as spirochetes.
Bacteria can live in almost any kind of environment, from extreme heat to intense cold, and some can even survive in radioactive waste. There are trillions of strains of bacteria, and few of these cause diseases in humans. Some of them live inside the human body without causing harm, for example in the gut or airways. Some "good" bacteria attack "bad" bacteria and prevent them from causing sickness. However, some bacterial diseases are deadly. These include: cholera, diphtheria, dysentery, bubonic plague, pneumonia, tuberculosis, typhoid, typhus, etc. Some examples of bacterial infections are: bacterial meningitis, otitis media, pneumonia, tuberculosis, upper respiratory tract infection, gastritis, food poisoning, eye infections, sinusitis, urinary tract infections, skin infections, sexually transmitted diseases, etc. Bacterial infections can be treated with antibiotics, but some strains become resistant and can survive the treatment.
(B) The nature of the invention and predictability in the art:
The invention is directed toward controlling all unwanted microorganisms and therefore is physiological in nature. It is well established that "the scope of enablement varies inversely with the degree of unpredictability of the factors involved," and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
(C)Direction or guidance:
That provided is very limited. The dosage range information is not found in the Specification. Thus, there is no specific direction or guidance regarding a regimen or dosage effective specifically for a method of treatment for a Gram-positive bacterial infection.
(D) State of the prior art:
The method of treating involves administering a composition of both a CgoX activator of substituted benzo-pyrazole compounds and a photosensitizer conjugated to a targeting moiety and irradiating with two wavelengths of light. So far as the examiner is aware, no dual combination of substituted benzo-pyrazoles/photosensitizer conjugated to a targeting moiety of any kind have been used for treating bacterial infections generally.
(E) Working examples:
The invention is drawn to a method of treating or skin or soft tissue infections generally. There are only six bacterial strains used in these studies and they found in the Specification on page 21, Table 1. They are all Staphylococcus aureus strains.
(F) Skill of those in the art:
Antibiotics are usually effective against either Gram-positive or Gram-negative bacteria. There are very few that have been able to treat both types of bacteria. These "super drugs" are usually kept for resistant strains because they are so valuable and hard to come by. Furthermore, there are no methods of compositions that can treat all infections (bacterial, viral, fungal) generally.
(G) The quantity of experimentation needed:
Owing especially to factors A, C, E and F, the amount of experimentation is expected to be high. MPEP 2164.01(a) states, "A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)." That conclusion is clearly justified here.
Written Description
Claims 22, 25-27, 34-42 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
This is a written description rejection.
The analysis for adequate written description considers the following:
(a) Actual reduction to practice;
(b) Disclosure of drawings or structural chemical formulas;
(c) Sufficient relevant identifying characteristics, such as (i) complete/partial structure, (ii) physical and/or chemical properties, and (iii) functional characteristics when coupled with known or disclosed correlation with structure; and
(d) Representative number of samples.
A lack of adequate written description issue arises if the knowledge and level of skill in the art would not permit one skilled in the art to immediately envisage the product claimed from the disclosed process. See, e.g., Fujikawa v. Wattanasin, 93 F.3d 1559, 1571,39 USPQ2d 1895, 1905 (Fed. Cir. 1996) (a "laundry list" disclosure of every possible moiety does not constitute a written description of every species in a genus because it would not "reasonably lead" those skilled in the art to any particular species); In re Ruschig, 379 F.2d 990, 995, 154 USPQ 118, 123 (CCPA 1967).
An applicant may also 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.
In particular, the specification as originally filed fails to provide sufficient written description to demonstrate possession of use of the broad term: coproporphyrinogen oxidase (CgoX) activator. The mere fact that Applicant may have discovered one specific type of CgoX activator that can be used to increase amounts of coproporphyrin III (CPIII) in a Gram-positive bacterial cell, is not sufficient to claim the entire genus. Applicant does not have support to claim the entire universe of CgoX activators, including those yet to be discovered. Claim 22 provides no guidance with respect to any specific CgoX activator until Claim 28. The specification, as filed, only has support for benzo-pyrazole derivatives, but with respect to “coproporphyrinogen oxidase (CgoX) activator”, there is no guidance within the base claim to limit the CgoX activator.
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, reduction to drawings, 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. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
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. 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]."
Thus, claims 22, 25-27, 34-42 are rejected under 35 USC 112(a), (Written Description).
Examiner Comments
The examiner notes that the present invention is directed to a method of treating a SSTI comprising administering a composition that has two methods of treatment. The first method of treatment is use of a CgoX activator, followed by irradiation with light of a certain wavelength. This component has been described fully by Surdel et al. However, the second half of the composition includes a photosensitizer (specifically IR700DX) conjugated to a monoclonal antibody that selectively binds iron-regulated surface determinant (Isd) proteins. As far as the examiner is aware, this has not been described in the literature, alone or in combination with a CgoX activator, before the effective filing date of the claimed invention.
The examiner acknowledges that Brezski et al. does disclose anti-staphylococcal monoclonal antibodies (CS-D7, IgG1) targeting IsdB, that were used as test articles (para 0198). Brezski et al. also (para 0094) recites: “In another embodiment, the second portion of the fusion construct comprises a pharmaceutically active moiety, such as, e.g., a cytokine, a toxin, a chemokine, an antibacterial peptide, an antibiotic, an enzyme, a peptide or protein with specific target binding characteristics, a fluorescent dye, a photosensitizer, a radionuclide, a contrast agent for medical imaging, a toxic compound, a pro-coagulant factor, an enzyme for pro-drug activation, an albumin binder, an albumin, an IgG binder or polyethylene glycol.” In yet another instance, the reference specification recites (para 0090): “The second portion of the fusion construct may comprise a second binding molecule, a pharmaceutically active moiety, a prodrug, a pharmaceutically-acceptable carrier, a diagnostic moiety, a cell penetrating enhancer moiety, a half-life extending modulating moiety, and any combination thereof” Altogether, these amount to merely a laundry list of possibilities. Brezski et al. provides no evidence that the authors developed an anti-staphylococcal monoclonal antibody conjugated to a photosensitizer and irradiated this with light of a certain wavelength with the express purpose of destroying Gram-positive bacteria. Furthermore, this conjugate was not administered together in combination with a CgoX activator before the effective filing date of the claimed invention.
Conclusion
No claims are allowed.
All claims are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LUKE ALAN BORALSKY whose telephone number is (571)272-9746. The examiner can normally be reached Monday - Friday 7:30 am - 5:00 am.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey H Murray can be reached at 571-272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/L.A.B./Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624