DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant's election with traverse of Group I (claims 1-7) in the reply filed on 6/22/2026 is acknowledged. The traversal is on the ground that there would be no serious burden involved in examination of both groups. This is not found persuasive because applicant's argument is merely speculative and not supported by probative evidence. There is no certainty that uncovering limitations in the protein crystal drug delivery system would necessarily lead to methods of making the protein crystal drug delivery system as claimed. The requirement is still deemed proper and is therefore made FINAL.
Claims 8-22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected group, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 6/22/2026.
Drawings
Figure 12 is labeled “Figs. 12” in the drawings, however, there appears to be only one singular Figure 12 (i.e. there is no Fig. 12a, Fig. 12b. etc.). The Specification also only references “FIG 12” which could potentially lead to confusion as to whether there are missing figures.
Specification
The disclosure is objected to because of the following informalities:
Page 2: “clustered regularly interspersed palindromic repeats” should be abbreviated as “CRISPR” instead of “CRISPER”.
Page 6: Figures 7A, 7B and 7C are described as having a scale bar. No scale bar appears visible.
Page 6: Figure 10B is described as “time course confocal images showing Nanoluciferase activity in a large crystal over ~13 minutes”. This seems incongruent as Figure 10B appears to be a bar graph. Figure 10C is also described as having a scale bar. No scale bar appears visible.
Pages 4, 5, 12 and 16: “Campylobacter jejeuni” should read “Campylobacter jejuni”.
Appropriate correction is required.
The use of the terms such as Coomassie Plus, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
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 errors of which applicant may become aware in the specification.
Claim Objections
Claim 1 is objected to because of the following informalities: Claim 1 recites “Campylobacter jejeuni” instead of “Campylobacter jejuni”. 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 1-7 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 1 recites “a nanoporous protein crystal derived from a polyisoprenoid-binding protein from Campylobacter jejeuni”. “Derived from” is a relative term which renders these claims indefinite. The term “derived from” is not defined by these claims, nor does the specification provide a standard for ascertaining the requisite or permitted degree of derivation. Thus, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. For instance, what amount of modification or deriving is permitted? Similarly, at what point is the modification so significant as to no longer be embraced by the phrase "derived from". It is unclear how far one can deviate from the parent protein without being so far removed therefrom as to be considered a different type of protein. Without a clear definition of the phrase “derived from”, one of skill in the art would be unable to determine the metes and bounds of the claimed invention.
Claim 1 also recites “a variant of a polyisoprenoid-binding protein from Campylobacter jejeuni”. Similar to the recitation of “derived from” discussed above, the term “variant” is not defined by the claims, nor does the specification provide a standard for ascertaining the requisite or permitted degree of variation. It is unclear how far one can deviate from the parent protein without being so far removed therefrom as to no longer be considered a variant of the parent protein. Without a clear definition of the phrase “variant”, one of skill in the art would be unable to determine the metes and bounds of the claimed invention.
Claim 1 also recites “(SEQ ID NO: 14)” and “(SEQ ID NO: 15)”. These render the claim indefinite because it is unclear if the parenthetical recitations are part of the claimed invention or merely recitations of examples/preferences. Description of examples or preferences is properly set forth in the specification rather than the claims. If stated in the claims, examples and preferences may lead to confusion over the intended scope of a claim. In those instances where it is not clear whether the claimed narrower range is a limitation, the claim is indefinite. MPEP 2173.05(d). For purposes of compact prosecution, if the prior art teaches a porous protein crystal of a polyisoprenoid-binding protein from Campylobacter jejuni, it will be considered to read on the claim limitations.
Claims 2-7 do not cure the deficiencies of claim 1 and thus are deficient for the same reasons.
Claim 4 recites “(SEQ ID NO: 13)”. This renders the claim indefinite because it is unclear if the parenthetical recitation is part of the claimed invention, or merely a recitation of an example/preference. Description of examples or preferences is properly set forth in the specification rather than the claims. If stated in the claims, examples and preferences may lead to confusion over the intended scope of a claim. In those instances where it is not clear whether the claimed narrower range is a limitation, the claim is indefinite. MPEP 2173.05(d). The instant specification seems to refer to the D2 domain from human N-ethylmaleimide sensitive factor using PCD code 1NSF and “SEQ ID NO: 13” interchangeably, despite the two sequences being different. Furthermore, paragraph 0055 of the specification refers to the protein sequences in Table 1 as “exemplary”. For purposes of compact prosecution, if the prior art teaches the D2 domain from human N-ethylmaleimide sensitive factor, it will be considered to meet the instant claim limitation.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1 and 2 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Snow et al. (US 2017/03262282), as evidenced by Collins Dictionary.
Regarding claim 1, Snow teaches a composition comprising a porous protein crystal with a pore size equal to or greater than 3 nanometers (reads on nanoporous) and a guest molecule that comprises a biomacromolecule [claim 1]. The porous protein crystal comprises a YCEI (i.e. polyisoprenoid-binding) protein from Campylobacter jejuni [claim 13], and the guest biomacromolecule may be a DNA or RNA sequence, protein, or enzyme [claim 10]. Snow further teaches that the porous protein crystal contains a binding site for the guest molecule within the pore [claim 14], and the guest molecule and crystal may be engineered to have a metal-affinity motif, which may comprise a peptide sequence with a histidine residue [claims 16-17]. The instant specification discusses guest molecule adsorption as being assisted by metal atoms that can bind histidine tags, and describes adsorbed guest molecules as “bound” [Instant Spec. para 0119]. Thus, disclosure of Snow reads on the instant limitation of “adsorbed”. Additionally, Snow explicitly states that the guest molecules are adsorbed into the protein crystal [0165].
Regarding claim 2, this claim recites the limitation wherein the nanopores of the protein crystal are obstructed. Under BRI, “obstructed” can be reasonably interpreted as being blocked from being seen in its entirety. See Collins Dictionary (accessed 8/21/20226). Under this interpretation, the presence of a guest molecule in the nanopore, by reason of its placement, would inherently obstruct the nanopores of the porous protein crystal.
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.
Claims 1-3 are rejected under 35 U.S.C. 103 as being unpatentable over Snow et al. (US2017/0362282, published 12/21/2017) in view of Vaghasiya et al. (2020) and Park et al. (2021).
Regarding claim 1, Snow teaches a composition comprising a porous protein crystal with a pore size equal to or greater than 3 nanometers (reads on nanoporous) and a guest molecule that comprises a biomacromolecule [claim 1]. The porous protein crystal comprises a YCEI (i.e. polyisoprenoid-binding) protein from Campylobacter jejuni [claim 13], and the guest biomacromolecule may be a DNA or RNA sequence, protein, or enzyme [claim 10]. Snow states that the guest molecules are adsorbed into the protein crystal [0165].
Regarding claims 2 and 3, these claims recite limitations wherein the nanopores of the protein crystal drug delivery system are obstructed (claim 2) with at least one capping protein (claim 3). Snow does not explicitly discuss the use of capping proteins. Vaghasiya teaches a controlled drug-delivery system comprising mesoporous silica nanoparticle carriers and the drug Cisplatin. The nanoparticles were surface-coated with collagen to form a capping layer that obstructed the pores of the carrier and constrained the Cisplatin within the nanocarrier pores [Abstract]. Vaghasiya teaches that the capping protein layer protected the Cisplatin from degradation that would otherwise result from the physiological conditions of the body, allowing for the drug to reach the intended target site. The physical entrapment of the drug also prevented unwanted drug leakage prior to reaching the intended target site [pg. 4993].
While the drug delivery carrier of Vaghasiya is not identical to that of the present invention, the teachings of Vaghasiya may nonetheless be properly applied as they are drawn to problems that are shared with the instantly claimed invention. See MPEP 2143(I)(C). The instant invention is drawn to guest molecules comprising nucleic acids and proteins. Park teaches that nucleic acids, RNA in particular, are unstable and prone to degradation by ubiquitous nucleases in vitro and in vivo [pg. 140]. Therapeutic applications of RNA and DNA therefore require the use of delivery vehicles that can provide protection from degradation [pg. 138; 140]. A skilled artisan would recognize the advantages of capping the pores of the drug delivery nanocarrier and accordingly modify the teachings of Snow with that of Vaghasiya, in order to predictably improve the drug delivery capabilities of the porous protein crystal. The addition of a capping protein would improve the selective drug targeting abilities of the drug delivery system and protect the nucleic acid guest molecules from degradation by nucleases and other physiological conditions in the body.
Claims 4 is rejected under 35 U.S.C. 103 as being unpatentable over Snow et al. (US2017/0362282, published 12/21/2017), in view of Vaghasiya et al. (2020) and Park et al. (available online 12/17/2020), as applied to claim 3 above, and further in view of RCSB Protein Data Bank, 1NSF (1998) and Masri (2022).
Regarding claim 4, claim 4 recites the limitation wherein the capping protein comprises the D2 domain from human N-ethylmaleimide sensitive factor (NSF). Snow teaches that the porous protein crystal comprising a polyisoprenoid-binding protein from Campylobacter jejuni has a hexagonal array of axial pores wherein the pore diameter is 13 nanometers [0027]. Snow does not disclose a capping protein comprising the D2 domain from human NSF. Masri discusses the selection process of capping protein candidates for a porous protein crystal comprising an isoprenoid-binding protein from Campylobacter jejuni [Abstract; pg. 30]. Masri discloses that the arrangement of histidine tags in a six-fold radially symmetric manner in the protein crystal pores suggested that a hexameric protein would be best suited to be the capping protein. Furthermore, the capping protein should have a diameter that ensures the obstruction of the majority of the pore opening, while being slightly undersized in order to allow the capping protein to fit [pg. 30]. Thus, it would be obvious to one of ordinary skill, to choose a capping protein from known proteins that possess the desired size and properties to allow for effective capping of the CJ crystal pore structure. It would be obvious to utilize any number of protein databases to identify suitable candidates. In this case, the RSCB Protein Data Bank entry for 1NSF (i.e. D2 domain of NSF) discloses that 1NSF is a hexameric protein with a diameter of 116 Å, which is equivalent to 11.6 nanometers, i.e. appropriately sized to obstruct a 13 nanometer pore. Thus, it would be obvious to try 1NSF as a capping protein for the porous CJ crystal due to its size and shape.
Claims 5-7 are rejected under 35 U.S.C. 103 as being unpatentable over Snow et al. (US2017/0362282, published 12/21/2017), as applied to claim 1 above, further in view of Sousa de Almeida et al. (published 3/5/2021), Kwon et. al (2014), and Vekilov (2010).
Regarding claims 5-7, these claims recite limitations relating to the particle size of the nanoporous protein crystal. Snow does not explicitly discuss the particle size of its nanoporous protein crystals. Sousa de Almeida describes endocytic pathways involved in the internalization of nanoparticles used in drug delivery applications [Abstract; Introduction] and teaches that endocytosis is the principal process used by cells to internalize nanoparticles [pg. 5399]. Size, in particular, is one of the most important parameters for endocytosis [pg. 5404; see also Fig. 1]. Particles larger than 500 nanometers are known to be internalized only through phagocytosis and micropinocytosis [pg. 5404]. Other endocytic mechanisms are limited to cargo particles with a maximum size of 200 to 300 nanometers [pg. 5404]. Where the range taught in the prior art overlaps with the instantly claimed range, a prima facie case of obviousness exists. MPEP 2144.05. It would be obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to apply the teachings of Sousa de Almeida to the invention of Snow, and formulate the porous crystal drug delivery system of Snow to be around 300 nanometers in order to avail the drug delivery system to endocytic mechanisms other than phagocytosis and micropinocytosis. In other words, a crystal of 300 nanometers would have wider clinical (and, in turn, commercial) applicability. Additionally, methods of protein crystallization, such as batch crystallization, are conventional and well-known in the art, wherein the size of a crystal structure may be adjusted and controlled by crystallization conditions such as temperature and solute concentration. See e.g., Kwon et. al (2014) and Vekilov (2010). Thus, a skilled artisan would be able to apply the teachings of Snow and Sousa de Almeida, and arrive at the instantly claimed invention through the application of conventional crystallization techniques.
Double Patenting
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 1-7 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-46 of U.S. Patent No. 10,590,176 (Snow et al., patented 3/17/2020).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the reference patent and the instant claims are both drawn to a porous protein crystal comprising a polyisoprenoid-binding protein from Campylobacter jejuni and a drug adsorbed to the crystal, wherein the drug comprises a guest macromolecule of nucleic acid, protein, or a combination thereof.
Conclusion
No claims are allowed.
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/AMANDA LYNN CHI/ Examiner, Art Unit 1613
/JENNIFER A BERRIOS/ Primary Examiner, Art Unit 1613
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