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 .
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-8 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon without significantly more. The claim(s) recite(s) “a plurality of inhibitors configured to bind to SARS-CoV-2 spike protein” or “a composition including one or more inhibitors configured to bind to SARS-CoV-2 spike protein”. The recitation(s) embrace at least heparin, which as explained by Ouyang, Yilan, et al. "Non-anticoagulant low molecular weight heparins for pharmaceutical applications." Journal of medicinal chemistry 62.2 (2019): 1067-1073 (Ouyang) is a natural product extracted from mast cell-rich tissues of food animals, such as porcine intestine, sheep intestine, and bovine intestine or lungs (page 1067); fucoidan, which as explained by Morya, V. K., Jungeun Kim, and Eun-Ki Kim. "Algal fucoidan: Structural and size-dependent bioactivities and their perspectives." Applied microbiology and biotechnology 93 (2012): 71-82 (Morya) is a natural product isolated from various sources such as brown algae, sea urchin, and sea cucumber (page 72); and RPI-27 or RPI-26, which as explained in the specification is extracted from the seaweed Saccharina japonica (page 9, paragraph [0017]). Heparin, fucoidan, RPI-27, or RPI-26 is a nature-based product, so it is compared to its closest naturally occurring counterpart (e.g., heparin, fucoidan, RPI-27, or RPI-26 in its natural state) to determine if it has markedly different characteristics. Because there is no indication in the record that isolation of heparin, fucoidan, RPI-27, or RPI-26 has resulted in a marked difference in structure, function, or other properties as compared to its counterpart, a composition comprising heparin, fucoidan, RPI-27, or RPI-26 is a product of nature exception. This judicial exception is not integrated into a practical application because merely combining the product of nature with one or more additional active ingredients, or one or more pharmaceutically acceptable adjuvants, diluents, excipients, carriers, or combination thereof does not add a meaningful limitation as it is merely a nominal or token extra-solution component of the claim, and is nothing more than an attempt to generally link the product of nature to a particular technological environment. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the formulation of a natural product with one or more pharmaceutically acceptable adjuvants, diluents, excipients, carriers, or combination thereof, or an additional active agent was a well-understood , routine, conventional activity previously engaged in by those in the relevant field.
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 1-20 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.
The recitation(s) “a plurality of inhibitors configured to bind to SARS-CoV-2 spike protein” or “a composition including one or more inhibitors configured to bind to SARS-CoV-2 spike protein” renders claims reading on said recitation(s) indefinite as this limitation merely states a functional characteristic without providing any indication about how the functional characteristic is provided. It is unclear whether a composition comprising any heparin compound or any fucoidan compound is embraced by said recitation(s) or if applicant intends to invention to require some other structure structural limitation such as specific arrangement/connection of saccharide units, molecular weight, extent of sulphuration, or existence/degree of branching, etc. There is nothing inherently wrong with defining some part of an invention in functional terms; however, a functional limitation must be evaluated and considered, just like any other limitation of the claim, for what it fairly conveys to a person of ordinary skill in the pertinent art in the context in which it is used. Functional descriptions of chemical compounds/compositions must be coupled with a known or disclosed correlation between function and structure.
For the purposes of applying prior art, the examiner interprets the recitation(s) to embrace a composition comprising any heparin or fucoidan compound.
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.
Claim(s) 1-2 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ouyang, Yilan, et al. "Non-anticoagulant low molecular weight heparins for pharmaceutical applications." Journal of medicinal chemistry 62.2 (2019): 1067-1073 (Ouyang).
Ouyang teaches that heparin is a polypharmacological agent with anticoagulant activity (Abstract). Periodate oxidation of the nonsulfated glucuronic acid residue results in non-anticoagulant heparin derivative (NACH) of reduced molecular weight. Similar treatment of a low molecular weight heparin, dalteparin, also removes its anticoagulant activity, affording a second heparin derivative (D-NACH) (e.g., a trisulfated heparin). A full structural characterization of these two derivatives reveals their structural differences. SPR studies display their ability to bind to several important heparin-binding proteins, suggesting potential new therapeutic applications.
NACH and D-NACH are embraced by “a plurality of inhibitors configured to bind to SARS-CoV-2 spike protein”. Ouyang teaches all of the instantly claimed elements. Thus, claims 1-2 are anticipated.
Claim(s) 1 and 8 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mycroft-West, Courtney, et al. "The 2019 coronavirus (SARS-CoV-2) surface protein (Spike) S1 Receptor Binding Domain undergoes conformational change upon heparin binding." BioRxiv (2020): 2020-02 (West).
West teaches that many pathogens take advantage of the dependence of the host on the interaction of hundreds of extracellular proteins with the glycosaminoglycans heparan sulfate to regulate homeostasis and use heparan sulfate as a means to adhere and gain access to cells (Abstract). Moreover, mucosal epithelia such as that of the respiratory tract are protected by a layer of mucin polysaccharides, which are usually sulfated. Consequently, the polydisperse, natural products of heparan sulfate and the allied polysaccharide, heparin have been found to be involved and prevent infection by a range of viruses including S-associated coronavirus strain HSR1. Here West uses surface plasmon resonance and circular dichroism to measure the interaction between the SARS-CoV2 Spike S1 protein receptor binding domain (SARS-CoV-2 S1 RBD) and heparin. The data demonstrate an interaction between the recombinant surface receptor binding domain and the polysaccharide. This has implications for the rapid development of a first-line therapeutic by repurposing heparin and for next-generation, tailor-made, GAG-based antivirals.
West teaches that glycosaminoglycans are ubiquitously present on almost all mammalian cells and this class of carbohydrates are central to the strategy employed by coronaviridae to attach to host cells (page 7). Heparin has previously been shown to inhibit SARS-associated coronavirus strain HSR1 cell invasion and this, in concert with the data presented within this study, supports the utilisation of glycosaminoglycan-derived pharmaceuticals against SARS-associated coronavirus. Furthermore, this study strongly supports the repurposing of heparin and its derivatives as antiviral agents, providing a rapid countermeasure against the current SARS-CoV-2 outbreak. West teaches that such drugs will be amenable to routine parenteral administration through currently established routes and additionally, direct to the respiratory tract via nasal administration, using nebulised heparin, which would be unlikely to gain significant access to the circulation.
West teaches that it is noteworthy that even pharmaceutical-grade heparin preparations remain a polydisperse mixture of natural products, containing both anticoagulant and nonanticoagulant saccharide structures. The latter may prove to be an invaluable resource for next-generation, biologically active, antiviral agents that display negligible anticoagulant potential, whilst the former remains tractable to facile, chemical (and enzymatic) engineering strategies to ablate their anticoagulation activities.
Heparin formulated for parenteral or nasal administration is embraced by “a plurality of inhibitors configured to bind to SARS-CoV-2 spike protein”. West teaches all of the instantly claimed elements. Thus, claims 1 and 8 are anticipated.
Claim Rejections - 35 USC § 103
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) 9 and 11-17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mycroft-West, Courtney, et al. "The 2019 coronavirus (SARS-CoV-2) surface protein (Spike) S1 Receptor Binding Domain undergoes conformational change upon heparin binding." BioRxiv (2020): 2020-02 (West) as applied to claims 1 and 8 above.
West differs from the instantly claimed invention in that West does not explicitly teach administering heparin to a patient identified as having a presence of SAR-CoV-2; however, this deficiency would have been prima facie obvious.
In considering the disclosure of a reference, it is proper to take into account not only specific teachings of the reference but also the inferences which one skilled in the art would reasonably be expected to draw therefrom. In the instant case, West reasonably suggests administering heparin to a patient identified as having a presence of SAR-CoV-2. West explicitly teaches that this study strongly supports the repurposing of heparin and its derivatives as antiviral agents, providing a rapid countermeasure against the current SARS-CoV-2 outbreak. West explicitly teaches that such drugs will be amenable to routine parenteral administration through currently established routes and additionally, direct to the respiratory tract via nasal administration, using nebulised heparin, which would be unlikely to gain significant access to the circulation.
With the teachings of West in hand, one of ordinary skill could have found the instantly claimed effective amount(s) via routine experimentation.
Thus, claims 9 and 11-17 would have been obvious based on the preponderance of evidence.
Claim(s) 10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mycroft-West, Courtney, et al. "The 2019 coronavirus (SARS-CoV-2) surface protein (Spike) S1 Receptor Binding Domain undergoes conformational change upon heparin binding." BioRxiv (2020): 2020-02 (West) as applied to claims 9 and 11-17 above, further in view of Ouyang, Yilan, et al. "Non-anticoagulant low molecular weight heparins for pharmaceutical applications." Journal of medicinal chemistry 62.2 (2019): 1067-1073 (Ouyang) as applied to claims 1-2 above.
West differs from the instantly claimed invention in that West does not explicitly teach a method wherein the one of more inhibitors includes unfractionated USP-heparin, a trisulfated (TriS) heparin, a non-anticoagulant low molecular weight heparin (NACH), or combinations thereof. However, this deficiency would have been obvious in view of the teachings of Ouyang.
It would have been obvious to substitute heparin with NACH in the method of West. West explicitly teaches that this study strongly supports the repurposing of heparin and its derivatives as antiviral agents, providing a rapid countermeasure against the current SARS-CoV-2 outbreak. West further teaches that it is noteworthy that even pharmaceutical-grade heparin preparations remain a polydisperse mixture of natural products, containing both anticoagulant and nonanticoagulant saccharide structures. The latter may prove to be an invaluable resource for next-generation, biologically active, antiviral agents that display negligible anticoagulant potential. While Ouyang teaches that NACH is a in non-anticoagulant heparin derivative (NACH). The simple substitution of one known element (heparin or a derivative thereof) for another to obtain predictable results is prima facie obvious. The rationale to support a conclusion that the claim would have been obvious is that the substitution of one known element for another yields predictable results to one of ordinary skill in the art.
Thus, claim 10 would have been obvious based on the preponderance of evidence.
Conclusion
Claims 1-20 are pending. Claims 1-20 are rejected. No claims are allowed.
Contacts
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PATRICK T LEWIS whose telephone number is (571)272-0655. The examiner can normally be reached Monday to Friday, 10 AM to 4 PM EST (Maxi Flex).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Renee Claytor can be reached at (571) 272-8394. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PATRICK T LEWIS/Primary Examiner, Art Unit 1691
/PL/
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