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 .
DETAILED ACTION
Response to Election/Restriction filed January 28, 2026 is acknowledged.
Claims 1-20 are pending in the current application.
Election/Restrictions
Applicant elected with traverse Group 2 (claims 5-12) and without traverse SEQ ID NO:1 from List I, SARS CoV2 from list II and dexamethasone from List III a in the response filed January 28, 2026.
The restriction is deemed proper and is made FINAL in this office action. Claims 1-4, 13-20 are withdrawn as being drawn to a non-elected species/invention. Claims 5-12 examined on the merits of this office action.
Claim Rejections - 35 USC § 112, first paragraph
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 5-12 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 treating SARS-CoV-2 with MASL not reasonably provide enablement for treating/preventing SARS-CoV-2 with any Lectin, variant or fragment thereof encompassed by the claims. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
To comply with the enablement requirements of 35 U.S.C. §112, first paragraph, a specification must adequately teach how to make and how to use a claimed invention throughout its scope, without undue experimentation. Plant Genetic Systems N.V. v. DeKalb Genetics Corp., 315 F.3d 1335, 1339, 65 USPQ2d 1452, 1455 (Fed. Cir. 2003). There are a variety of factors which may be considered in determining whether a disclosure would require undue experimentation. These factors include: (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
The Nature of the Invention/ The breadth of the claims
The claims are drawn to “A method of treating, preventing, and/or ameliorating a SARS-CoV-2 infection, the method comprising administering to the subject a pharmaceutical composition comprising at least one pharmaceutically acceptable carrier and a therapeutically effective amount of a lectin” (Claim 5). The claims are further drawn to wherein the lectin is not limited to a single species comprises sequences having at least 90% similarity to SEQ ID NO:1 and/or comprises a biologically active fragment of SEQ ID NO:1.
Thus the claims encompass a diverse lectin species, sequences having greater than 90% similarity to SEQ ID NO:1 and biologically active fragments thereof. Lectins are a large and structurally diverse protein class with differing binding specificities, tissue interactions, pharmacokinetics and biological effects. The genus include numerous unrelated proteins from different organisms. Thus, the scope of the claims is extremely broad relative to the specific embodiments disclosed.
The State of the Prior Art
The invention concerns biologic therapeutic methods for treating or preventing SARS CoV-2 infection using lectin proteins. Therapeutic antiviral treatment using protein agents involves complex and unpredictable variables including protein binding specificity, off target effects, immunogenicity, toxicity, in vivo delivery, pharmacodynamics and pharmacokinetics, virus host interaction variability. More than 500 purified lectins originated from plants, animals and microbes. Lectins are classified based on many aspects such as; origin, carbohydrate specificity, folds and three-dimensional structure, presence and localization, structure-function specificity etc. There is no single universally accepted classification of lectin, but we collected the main classifications of lectins in Table 2” (see section 4.2). Thus, lectins are structurally and functionally diverse and therapeutic efficacy across a broad genus is considered unpredictable.
The Predictability or Unpredictability of the Art/ The Relative Skill of Those in the Art
Protein therapeutics and antiviral treatment are unpredictable arts. Small sequence changes or different lectin family members can produce markedly different binding properties, cell responses, toxicities and therapeutic outcomes. The specification provides no evidence that activity against SARS-CoV-2 is predictable across the lectin genus or across sequence variants and fragments.
A person of ordinary skill in the art would likely have advanced training in molecular biology, virology or protein therapeutics. However, even with such skill, predicting which lectins across a broad genus would be safe and effective SARS-CoV-2 therapeutics would require extensive screening and testing. High skill in the art does not overcome the absence of guidance across the full claimed genus in an unpredictable field.
Amount of Guidance/ The Presence or Absence of Working Examples
The specification provides experimental guidance only for MASL. The disclosure includes MASL cell based assays, MASL effects on ACE2, inflammatory signaling, and viral spike binding, MASL dosing in vitro. The specification does not provide guidance for selecting other lectins for SARS-CoV-2 treatment, predicting which lectins will have the claimed effect, modifying lectins while retaining activity, identifying which fragments are active, determining which greater than 90% sequence identity similarity variants retain therapeutic efficacy. No screening framework or decision criteria are provided that would allow the skilled artisan to identify operable species across the full scope without extensive experimentation. Working examples are provided only for one lectin species (MASL) and only in cell based experimental systems. No working examples are provided for other lectins, variant sequences, fragments, in vivo SARS-CoV-2 treatment or prevention in subjects, clinical or animal infection models demonstrating treatment or prevention. Where claims cover a broad genus but only a single species is enabled, this factor weights against enablement of the full scope.
The Quantity of Experimentation Necessary
Considering the factors above, the skilled artisan would be burdened with undue experimentation in determining if one of the lectin/variants/fragments would be effective at treating/preventing SARS-CoV-2. The experimentation required represents years of inventive effort. When the above factors are weighed, it is the examiner's position that one skilled in the art could not practice the invention without undue experimentation.
Therefore, in view of the Wands factors, the claims appear to require undue experimentation to use the full scope of the claimed invention.
Claims 5-12 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.
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.
Scope of the claims
The claims are drawn to “A method of treating, preventing, and/or ameliorating a SARS-CoV-2 infection, the method comprising administering to the subject a pharmaceutical composition comprising at least one pharmaceutically acceptable carrier and a therapeutically effective amount of a lectin” (Claim 5). The claims are further drawn to wherein the lectin is not limited to a single species comprises sequences having at least 90% similarity to SEQ ID NO:1 and/or comprises a biologically active fragment of SEQ ID NO:1. Thus, the claims encompass a broad genus of lectins, as well as a genus of sequence variants and fragment species defined primarily by percent similarity and functional activity rather than specific disclosed structures. Accordingly the claims subject matter extends beyond a single disclosed lectin protein sequence and includes numerous structural distinct proteins and truncated forms thereof.
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. The specification provides experimental data demonstrating biological activity only for MASL corresponding to SEQ ID NO:1. The working examples and figures described MASL treatment in cell systems and report effects on ACE2 expression, glycosylation pathways, inflammatory signaling and SARS-CoV-2 related pathways. There are no experiments provided for other lectin species (with more than 500 lectins from plants, animals and microbes, see El Mardny et al, attached, section 4.2), sequences having greater than 90% similarity to SEQ ID NO:1, truncated MASL fragments or modified MASL proteins. Thus, the only subject matter actually reduced to practice is Full length MASL.
One of ordinary skill in the art would not consider the examples provided in the instant specification to be representative of the full scope of the claimed genus.
Therefore, the instant specification has failed to meet the written description requirement by actual reduction to practice of a representative number of species alone.
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.
In the instant case, the specification does not provide sufficient identifying characteristics for the Lectin Genus, the fragments and the greater than 90% sequence similarity variants. Lectins constituted a structurally diverse class of carbohydrate binding proteins derived from many species and having differing sequences and binding specificities (see attached handout, El Mardny). The specification provides only a single identified lectin species (MASL) and does not described representative lectin species across the genus, shared structural motifs required for the claimed therapeutic activity, consensus sequence features, lectin subclass tied to function in the claimed methods. Although the specification states that sequences having about 90-99% similarity to SEQ ID NO:1 are included, it does not disclose any actual variant sequences, permissible substitution patterns, conserved residues or critical binding regions. A statement of percent similarity without structural guidance or representative species, does not constitute a sufficient identifying characteristics of the claimed variant genus. The specification further refers to “biologically active fragments” but does not identify fragment lengths, domain boundaries, required residues, minimal functional regions or representative fragment species.
The specification lacks sufficient structural identifying characteristics of the lectins that would retain the desired functional activity of treating SARS-CoV-2 infection.
Physical and/or chemical properties:
The specification does not described any physical or chemical properties of the broader claimed lectin genus, variant sequences or fragments sufficient to distinguish which members fall within the claimed scope and possess the recited activity. There is no disclosure of structural domains responsible for activity, binding requirements, glycan binding, sequence structure constraints tied to the antiviral activity. Other than a single MASL protein, no structural property framework is provided to define the broader claimed classes.
Functional characteristics when coupled with a known or disclosed correlation between function and structure:
Functional data are provided only for full length MASL. The specification does not establish disclosed or known correlation between lectin structure generally and the claimed therapeutic effects or MASL sequence features and the desired biological activities. No structure/function correlation is provided that would allow a skilled artisan to recognize which other lectins, variants or fragments would be expected to have the claimed functional activity. Functional language without a demonstrated correlation to structure across the claimed scope is insufficient to establish possession of the claimed genus.
Method of Making
The specification does not describe methods of making variant sequences meeting the greater than 90% similarity limitation with retained activity, biologically active fragments, modified lectins within the claimed genus nor does it provide engineering guidance linking sequence modification to retained function. Absence of such disclosure further indicates lack of possession of the full claimed scope.
Thus, given the breadth of the claims, lack of structure in general, the lack of guidance in the specification regarding a structure/function correlation, it is not possible for one of ordinary skill in the art to determine what lectin (variants/fragments thereof) encompassed within the claimed genus would have the desired functional property.
Conclusion
The specification demonstrates possession only of full length MASL (SEQ ID NO:1). The claims however, encompass a broad genus of lectins, sequences having at least about 90% similarity to SEQ ID NO:1 and biologically active fragments thereof. Because the disclosure does not provide representative species, structural identifying features or a structure function correlation sufficient to show possession of these broader genera, the specification does not reasonably convey to one of ordinary skill in the art that the inventors had possession of the full claimed scope at the time of filing.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 8 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 5 claims “A method of treating….therapeutically effective amount of a lectin”. Claim 6, dependent on claim 5, claims “wherein the lectin is Maacki amurensis seed lectin MASL”. Claim 8 claims “wherein the MASL comprises an amino acid sequence having SEQ ID NO:1 or a biologically active fragment thereof”. Since the lectin is MASL in claim 6 (which is SEQ ID NO:1), a fragment of the lectin cannot be MASL as claimed in claim 6, and thus the dependent claim does not further limit the parent claim and instead broadens its scope.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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(s) 5 and 11-12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Liu (Liu et al., 2020, Cell Reports 32, 108016, published 8/2020).
Liu teaches that the plant lectin FRIL is a glycan binding lectin that exhibits antiviral activity against respiratory viruses. Liu demonstrates that FRIL inhibits virus entry by bonding complex N-glycans and shows in vivo efficacy when administered to mice infected with H1N1 influenza virus. Liu further teaches that FRIL inhibits SARS CoV 2 infection in vitro and identifies FRIL as a candidate antiviral agent for use in the COVID-19 pandemic. Liu suggests therapeutic and prophylactic applications, including inhalation and aerosol delivery formats to reduce viral infection and transmission (see conclusion paragraph, see also “In brief”).
Liu is silent to administering the lectin to a subject in a pharmaceutical formulation for treating SARS-CoV-2 infection.
It would have been obvious before the effective filing date of the claimed invention to use the lectin taught by Liu for treatment of SARS-CoV-2 infection by administration in a pharmaceutical formulation to a subject. One of ordinary skill in the art would have been motivated to do so given that Liu teaches that the lectin is effective at inhibiting SARS-CoV-2 infection, together with Liu’s disclosure of in vivo antiviral efficacy against a respiratory virus and Liu’s express identification of the Lectin as a COVID-19 therapeutic candidate. Given Liu’s demonstrated antiviral activity, shared viral entry inhibition mechanism and specific SARS-CoV-2 inhibition results, a person of ordinary skill in the art would have had a reasonable expectation of success in administering the lectin for treatment SARS-CoV-2.
Regarding use in pharmaceutical formulation and carrier, it would have been obvious before the effective filing date of the claimed invention to formulate Liu’s lectin in a pharmaceutical composition comprising a pharmaceutically acceptable carrier, because therapeutic proteins are routinely formulated with such carriers to enable safe and effective administration Applying standard pharmaceutical formulation techniques to a known antiviral lectin for its intended therapeutic use represents the application of known technique to achieve a predictable results and is therefore obvious under KSR (see MPEP2143).
Regarding claim 11, Liu teaches use of the lectin as an anti-viral agent against SARS CoV-2. It was well known in the art that SARS CoV-2 infection can lead to severe inflammatory complications including cytokine storm and acute respiratory distress syndrome (ARDS). It would have been obvious that treating or preventing SARS-CoV-2 infection with Liu’s antiviral lectin would reduce or ameliorate such known downstream complications, since reduction of viral infection predictably reduces associated inflammatory sequelae. Therefore, the additional patient condition limitation does not render the claim nonobvious.
Regarding claim 12, Liu teaches the lectin as a therapeutic and preventive candidate for COVID-19. COVID-19 is a human disease, and Liu’s discussion of clinical and prophylactic use provides motivation to administer the lectin to human subjects. The use of animal antiviral data to support human therapeutic application is well established in the art. Limiting the subject to a human therefore represents an obvious and expected application of Liu’s antiviral lectin therapy and is suggested by Liu.
Claim(s) 5 and 9-12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Liu (Liu et al., 2020, Cell Reports 32, 108016, published 8/2020) in view of Horby (July 2020, N Engl J Med 2021;384:693-704).
The teachings of Liu are provided in the above rejection. Liu is silent to including an additional therapeutic agent such as dexamethasone.
Horby teaches Dexamethasone for treatment of COVID-19. Horby teaches that dexamethasone improved survival and outcome in patients with COVID-19 (see Conclusions, page 693).
“It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose (treating COVID-19), in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious). But see In re Geiger, 815 F.2d 686, 2 USPQ2d 1276 (Fed. Cir. 1987) (“Based upon the prior art and the fact that each of the three components of the composition used in the claimed method is conventionally employed in the art for treating cooling water systems, the board held that it would have been prima facie obvious, within the meaning of 35 U.S.C. 103, to employ these components in combination for their known functions and to optimize the amount of each additive....Appellant argues... hindsight reconstruction or at best,... obvious to try’.... We agree with appellant.”). One of ordinary skilled in the art would have been motivated to combine the two each known to be useful for the same purpose (treating COVID19), with a reasonable expectation that at least here will be an additive effect.
Claim(s) 5-8 and 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over Liu (Liu et al., 2020, Cell Reports 32, 108016, published 8/2020) in view of Goldberg (US20120010152).
The teachings of Liu are provided in the above rejection. Liu is silent to wherein the lectin is Maacki amurensis seed lectin (MASL).
Goldberg teaches that lectins are carbohydrate binding proteins and specifically teaches plant lectin from Maackia amurensis (instant SEQ ID NO:1) that bind sialic acid and other glycans (see SEQ ID NO:23, claim 15, paragraph 0009, 0018). Goldberg further teaches pharmaceutical formulations comprising such lectin and their in vivo administration for biological effects (claim 15).
Because Liu teaches that lectin antiviral activity against SARS CoV-2 is mediated through glycan binding and inhibition of viral entry, and Goldberg teaches that MASL is a glycan biding lectin suitable for pharmaceutical administration, it would have been obvious before the effective filing date of the invention to use MASL as the lectin in Lius SARS-CoV-2 treatment method. A person of ordinary skill in the art would have been motivated to substitute one known glycan binding lectin (MASL) for another (FRIL) to achieve the same antiviral entry inhibition effect, with a reasonable expectation of success, since both belong to the same class of carbohydrate binding lectins and operate through the same recognized binding mechanism. Such substitution of one known equivalent lectin for another to obtain a predictable antiviral effect represents a predictable variation under KSR (see MPEP 2143).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERINNE R DABKOWSKI whose telephone number is (571)272-1829. The examiner can normally be reached Monday-Friday 7:30-5:30 Est.
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/ERINNE R DABKOWSKI/Examiner, Art Unit 1654