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 Status
Claims 37, 39-45, 47-49 and 52-59 are pending.
Claims 52-56 are withdrawn.
Claims 37, 39-45, 47-49, and 57-59 are under examination.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 9th, March, 2026 has been entered.
Withdrawn Claim Objections
The objection to claim 57 due to informalities as set forth in the previous office action is withdrawn in view of Applicant’s amendments.
New Claim Objections
Claim 37 is objected to because of the following informalities:
Claim 37 contains multiple conjunctions before each wherein clause and is therefore a run-on sentence.
Appropriate correction is required.
Withdrawn Claim Rejections - 35 USC § 112(a)
The rejection of claims 37, 39, 41-45, 47-49, and 57 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the written description requirement due to the presence of new matter as set forth in the previous office action is withdrawn in view of Applicant’s amendments.
Written Description
The rejection of claims 46 and 51 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 due to the presence of new matter as set forth in the previous office action is moot in view of the cancellation of these claims.
Moot Claim Rejections - 35 USC § 112(a)
Written Description
The rejection of claims 46 and 51 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 due to the presence of new matter as set forth in the previous office action is moot in view of the cancellation of these claims.
Claim Rejections - 35 USC § 112(a)
Written Description
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 40 and 58 remain 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
In the amendment filed on 9th, March, 2026 the claims were amended to recite the following new limitations which appear to be new matter. A review of the originally filed specification by the Examiner did NOT find any specific basis for the recited limitations. The disclosure (including the specification, claims and sequence listing) as originally filed, does not contain a specific recitation of the limitations.
The limitations which appear to be new matter and the closest support for the newly claimed limitations, which is insufficient to provide possession of the claimed limitations are discussed further below.
Dependent Claims
“between 1 :1.2 and 1 :1.4” (instant claim 40)
There is no specific disclosure of this range. The closest support for this limitation is in original claim 34, which states a balanced “charge:charge ratio of 1:1.” The recitation of a specific charge:charge ratio of 1:1, which is one specific point, does not provide support for the broader claimed range of “between 1 :1.2 and 1 :1.4” (see MPEP 2163.05 (III) Range Limitations).
“a peptide that has at least 90% identity with a peptide selected from the group consisting
of:
(i) (H-Dab-His-Dab-His-His-Dab-His-His-Dab-His-His-Dab-His-His-Dab-His-His-Dab-HisDab)
4-Lys-Lys-Lys-His-His-His-His-Asn-His-His-His-His-Arg-Arg-Arg-Arg-Arg-Arg-Arg-ArgOH;
(ii) (H-Dab-His-Dab-His-His-Dab-His-His-Dab-His-His-Dab-His-His-Dab-His-His-Dab-HisDab)
4-Lys-Lys-Lys-His-His-His-His-Asn-His-His-His-His-OH;
(iii) (H-Dab-His-Dab-His-His-Dab-His-His-Dab-His-His-Dab-His-His-Dab-His-His-Dab-HisHis-
Dab-His-His-Dab-His-His-Dab-His-His-Dab-His-His-Dab-His-Dab)4-Lys-Lys-Lys-HisHis-
His-His-Asn-His-His-His-His-OH;
(iv) (H-Dab-His-Dab-His-Dab-His-Dab-His-Dab-His-Dab-His-Dab-His-Dab-His-Dab- His-His-
Dab)4-Lys-Lys-Lys-His-His-His-His-Asn-His-His-His-His-OH;
(v) (H-Dab-His-His-Dab-His-His-Dab-His-His-Dab-His-His-Dab-His-His-Dab-His-His-DabHis-
His-Dab-His-Dab)4-Lys-Lys-Lys-His-His-His-His-Asn-His-His-His-His-OH;
(vi) (H-Dab-His-His-Dab-His-His-His-Dab-His-His-Dab-His-His-His-Dab-His-His-Dab-HisHis-
His-Dab-His-His-Dab-His-Dab)4-Lys-Lys-Lys-His-His-His-His-Asn-His-His-His-His-OH;
and
(vii) (H-Dap-His-Dap-His-His-Dap-His-His-Dap-His-His-Dap-His-His-Dap-His-His-Dap-HisDap)
4-Lys-Lys-Lys-His-His-His-His-Asn-His-His-His-His-OH” (instant claim 58).
There is not support for these specific branched cationic peptides in the disclosure and there is not support for sequences 90% identical to these sequences in the disclosure, which encompasses up to 10% of each of these sequences to be changed to all possible natural or unnatural amino acids and encompasses a very large number of structurally and functionally distinct branched cationic peptides. The closest support is disclosure of 12 structurally and functionally distinct cationic peptides (see Table 1) that do not provide support for these 7 peptides because they are structurally and functionally distinct, and there is not specific guidance provided in the specification that would lead one or ordinary skill to arrive at these specific sequences or any one of the vast number of sequences that are 90% identical to these 7 sequences from the general disclosure of cationic peptides that are branched and include a lysine core and His as well as Dab or Dap or from the disclosure of 12 specific structurally and functionally distinct sequences.
In Purdue Pharma L.P. v. Faulding Inc. 230 F.3d 1320, 1326, 56 USPQ2d 1481, 1486 (Fed. Cir. 2000), the Courts noted that “with respect In re Ruschig 379 F.2d 990, 154 USPQ 118 (CCPA 1967), Ruschig makes clear that one cannot disclose a forest in the original application, and then later pick a tree out of the forest and say “here is my invention.” In order to satisfy written description requirement, the blaze marks directing the skilled artisan to that tree must be in the originally filed disclosure.” In this regard, the general disclosure of cationic peptides does not satisfy the written description requirement for the branched peptides (ii)-(Iv) as claimed because there was no explicit or implicit disclosure of the branched peptides (ii)-(Iv) in the originally filed specification (i.e. blaze marks directing the skilled artisan to the tree in the forest).
As noted by MPEP 608.04(a), new matter includes not only the addition of wholly unsupported subject matter, but may also include adding specific percentages or compounds after a broader original disclosure, or even the omission of a step from a method. In the instant case, for the reasons stated above, a person of ordinary skill in the art would not consider the full breadth of the limitations discussed above to be explicitly, implicitly, or inherently supported by Applicant’s disclosure.
Furthermore, Applicant has not provided the specific location of support for the amendments to include the limitations discussed above. When filing an amendment an applicant should show support in the original disclosure for new or amended claims. See MPEP §§ 714.02 and 2163.06 ("Applicant should ... specifically point out the support for any amendments made to the disclosure.") The claim is a new or amended claim, the support for the limitation is not apparent, and applicant has not pointed out where the limitation is supported (see MPEP 2163 (I)).
Hence, there is insufficient written descriptions support for the instantly claimed limitation of and Applicant has not shown possession of the invention.
Response to Arguments
Applicant’s arguments, filed 9th, March, 2026, have been fully considered but are not found persuasive.
Applicant argues “The claim amendments presented herein include no new matter and are fully
supported by the specification of the above-identified application” (pg. 8).
In response, as stated above and as set forth previously, when filing an amendment an applicant should show support in the original disclosure for new or amended claims. See MPEP §§ 714.02 and 2163.06 ("Applicant should ... specifically point out the support for any amendments made to the disclosure."). Merely stating support is in the specification is not sufficient to “specifically point out the support.”
The claim is a new or amended claim, the support for the limitation is not apparent, and applicant has not pointed out where the limitation is supported, and therefore the limitations appear to be new matter for the reasons stated above (see MPEP 2163 (I)).
Claim Rejections - 35 USC § 112(a)
Written Description
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 37, 39-49, 51 and 57-58 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
As set forth below, the specific claim language which present written description issues is preset in independent claim 37 and dependent claim 58. By nature of their ultimate dependency on claim 37, claims 39-49, 51 and 57-58 are also rejected. Claim 58 is rejected because it is dependent on claim 37 and also because it presents additional written description issues below.
The purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997).
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include a disclosure of a representative number of species to describe the complete structure of the claimed genus and/or disclosure of a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof.
Scope of the Claims
In the instant case, the genera that present written description issues are:
Nanoparticles comprising 2-, 3-, 4-, or 5-branched cationic peptides comprising a lysine (K) core and at least two different amino acids selected from the group consisting of: histidine (H) and 2,3-diaminopropionic acid or 2,4-diaminobutyric acid (instant claim 37).
The broadest reasonable interpretation of the scope of this genus encompasses an unfathomably large number of structurally and functionally distinct cationic peptides. These cationic peptides encompass all possible lengths of cationic peptides with all possible combinations of branches of all possible lengths that may include all possible amino acids, standard or non-standard, as long as it otherwise meets the recited claim limitations. To illustrate the breadth of this, an example can be made with a 100 amino acid sequence using only standard amino acid , which would have 2095 options including a three-lysine core, one histidine, and one of either Dab or Dap, which is an enormously large amount of options. Since instant claims encompass all possible non-standard amino acids as well, they encompass hundreds of options rather than the standard 20 amino acids. Taken together with the claims also encompass all possible lengths and all possible combinations of branches with all possible sequences, this encompasses an unfathomably larger number of structurally and functionally distinct sequences.
Cationic peptides with at least 90% identity to a peptide selected from the group consisting
of:
(i) (H-Dab-His-Dab-His-His-Dab-His-His-Dab-His-His-Dab-His-His-Dab-His-His-Dab-His-Dab)4-Lys-Lys-Lys-His-His-His-His-Asn-His-His-His-His-Arg-Arg-Arg-Arg-Arg-Arg-Arg-ArgOH;
(ii) (H-Dab-His-Dab-His-His-Dab-His-His-Dab-His-His-Dab-His-His-Dab-His-His-Dab-His-Dab)4-Lys-Lys-Lys-His-His-His-His-Asn-His-His-His-His-OH;
(iii) (H-Dab-His-Dab-His-His-Dab-His-His-Dab-His-His-Dab-His-His-Dab-His-His-Dab-His-His-Dab-His-His-Dab-His-His-Dab-His-His-Dab-His-His-Dab-His-Dab)4-Lys-Lys-Lys-His-His-His-His-Asn-His-His-His-His-OH;
(iv) (H-Dab-His-Dab-His-Dab-His-Dab-His-Dab-His-Dab-His-Dab-His-Dab-His-Dab- His-His-
Dab)4-Lys-Lys-Lys-His-His-His-His-Asn-His-His-His-His-OH;
(v) (H-Dab-His-His-Dab-His-His-Dab-His-His-Dab-His-His-Dab-His-His-Dab-His-His-Dab-His- His-Dab-His-Dab)4-Lys-Lys-Lys-His-His-His-His-Asn-His-His-His-His-OH;
(vi) (H-Dab-His-His-Dab-His-His-His-Dab-His-His-Dab-His-His-His-Dab-His-His-Dab-His-His-
His-Dab-His-His-Dab-His-Dab)4-Lys-Lys-Lys-His-His-His-His-Asn-His-His-His-His-OH;
and
(vii) (H-Dap-His-Dap-His-His-Dap-His-His-Dap-His-His-Dap-His-His-Dap-His-His-Dap-His-Dap)4-Lys-Lys-Lys-His-His-His-His-Asn-His-His-His-His-OH (instant dependent claim 58).
This encompasses these specific cationic branched peptides as well as all possible sequences that are 90% or more identical to these sequences. This encompasses all possible substitutions with all possible standard or non-standard amino acids for all possible locations in each of these branches sequences, and further encompasses insertions or deletions of all possible sizes at all possible locations in these branched sequences that lead to 90% sequence identity.
To demonstrate the breadth of these genera, an example estimate can be made for the branched sequence of (i) (H-Dab-His-Dab-His-His-Dab-His-His-Dab-His-His-Dab-His-His-Dab-His-His-Dab-HisDab)4-Lys-Lys-Lys-His-His-His-His-Asn-His-His-His-His-Arg-Arg-Arg-Arg-Arg-Arg-Arg-ArgOH. This sequence recites 100 specific amino acids with specific locations in the branched peptide (4 branches of 20 amino acids and 1 tail with 20 amino acids). Estimating using the 20 standard amino acids, substitutions encompass up to 10 mismatches, which encompasses 2010 possible combinations. This very large number of structurally and functionally distinct sequences is also a gross underestimate of what is encompassed by applicant’s claim because the claim encompasses non-standard amino acids as well as insertions and deletions. Therefore, the breadth of sequences 90% or more identical to those recited in claim 58 encompasses an enormously large number of structurally and functionally distinct sequences.
Disclosure of Structure and Disclosure of Species
Regarding the cationic peptides, while Applicant generally contemplates the very broad genera of branched cationic peptides comprising a lysine core and at least two different amino acids selected from the group consisting of: histidine (H) and one of Dap or Dab (see, for example, para. [0007]), there is no specific disclose of specific sequences that meet these criteria and there is no disclosure of sequences with 90% or more sequence identity to the sequences (i) to (vii) of claim 58. Therefore, no specific species of the claims are disclosed.
Applicant discloses 12 specific cationic peptides (Table 1), that are structurally and functionally distinct peptides and cannot provide support for the specific and structurally distinct peptides recited as sequences (i) to (vii) of claim 58 or the more broadly claimed sequences of claim 37 because these 12 specific cationic peptides do not include one of Dap or Dab.
Because 0 specific species are disclosed, there is no support for sequences 90% or more identical to sequences (i) to (vii) of claim 58 and there is insufficient support for sequences comprising 2-, 3-, 4-, or 5-branched cationic peptides comprising a lysine (K) core and at least two different amino acids selected from the group consisting of: histidine (H) and 2,3-diaminopropionic acid or 2,4-diaminobutyric acid as recited in claim 37.
Structure/Function Correlation
Regarding the cationic peptides, is well known in the art that single changes in amino acids can affect the function of the peptide. Regarding cationic peptides as part of a nanoparticle specifically, Applicant is directed to the art of Leng et al. (Mol Ther. 2012 Dec;20(12):2282-90.; see IDS filed 9th, February, 2021; henceforth “Leng2”). Leng2 evidences structurally distinct branched cationic peptides as part of siRNA nanoplexes (Figure 1; Table 2). Leng2 evidences that similar, but structurally distinct, cationic peptides have functionally distinct properties as part of these nanoplexes (different cytokine inductions Figure 2). Leng2 evidences slight changes in the peptide sequences (addition of histidine rich tail), resulted in histidine-rich tails and thus higher buffering capacity induced lower levels of cytokines in mice compared with their parent peptides (pg. 2285 col. 2 1st para.).
Importantly, the art of Leng2 evidences that changes in the amino acid sequence of cationic peptides as part of nanoparticles has functional effects on peptide. In other words, Leng evidences that structurally distinct cationic peptides, even when similar (see, for example, H3K4b versus H3K(+H)4b; Figure 1), are functionally distinct.
Therefore, because the relationship between the structure of a branches cationic peptide and the function of that peptide is not predictable, and neither the specification or the art provide a clear nexus, one of ordinary skill cannot envision the requisite structural elements of the cationic peptides from the instant disclosure at the time of filing.
Written Description - Conclusion
Therefore, the examiner concludes there is insufficient written description support for the instantly claimed genera. Specifically, there is no description of specific sequences that are 2-, 3-, 4-, or 5-branched cationic peptides comprising a lysine (K) core and at least two different amino acids selected from the group consisting of: histidine (H) and 2,3-diaminopropionic acid or 2,4-diaminobutyric acid as required by claim 37 and there is no description of specific sequences that are 90% or more identical to sequences (i) to (vii) of claim 58. There is no description of the structure/function correlation that would allow one of ordinary skill in the art to reasonably ascertain which substitutions, deletions or insertions can be performed. As such, one of ordinary skill in the art could not envision all the embodiments that fall outside of the description provide by the specification and the art.
Withdrawn Claim Rejections - 35 USC § 112(b)
The rejection of claims 42 and 57 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite as set forth in the previous office action is withdrawn in view of Applicant’s amendments.
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 37, 39-45, 47-49, and 57-59 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 37 recites “two different amino acids selected from the group consisting of: histidine (H) and one of 2,3-diaminopropionic acid ("Dap") or 2,4-diaminobutyric acid ("Dab")” which appears to recite a Markush list (i.e. “selected from the group consisting of”) but requires two from the list and also does not recite a list of alternatively usable members. This is indefinite because it is unclear whether the list is intended to be a Markush and also it is unclear whether histidine (H), 2,3-diaminopropionic acid ("Dap") and 2,4-diaminobutyric acid ("Dab")” are alternative options, or whether histidine is required and dab and dap are alternative options.
Claim 37 recites “the nucleic acid is plasmid DNA and is a functional nucleic acid,” and also later recites “the nucleic acid is functional for transfection into a cell” which makes the scope of the claim unclear because “functional nucleic acid” broadly encompasses all possible functions including solely hybridization, while “functional for transfection into a cell” is more specific and requires the nucleic acid is able to be transfected into a cell. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) is considered indefinite, since the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). Note the explanation given by the Board of Patent Appeals and Interferences in Ex parte Wu, 10 USPQ2d 2031, 2033 (Bd. Pat. App. & Inter. 1989), as to where broad language is followed by "such as" and then narrow language. The Board stated that this can render a claim indefinite by raising a question or doubt as to whether the feature introduced by such language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Note also, for example, the decisions of Ex parte Steigewald, 131 USPQ 74 (Bd. App. 1961); Ex parte Hall, 83 USPQ 38 (Bd. App. 1948); and Ex parte Hasche, 86 USPQ 481 (Bd. App. 1949). In the present instance, claim 37 recites the broad recitation “functional nucleic acid”, and the claim also recites “functional for transfection into a cell” which is the narrower statement of the range/limitation.
Claim 37 recites “the nucleic acid” which appears to attempt to refer back to “a nucleic acid,” which is recited in the preamble of the claim. However, the preamble recites an intended use of “for transfection of a cell with a nucleic acid” and therefore the body of the claim, which refers to “the nucleic acid” attempts to refer back to an intended use and not to a required structure of the claim. Therefore, the scope of “the nucleic acid” is unclear because there is improper antecedent basis for this term and in is unclear whether the nucleic acid is intended to be a required element of the claimed nanoparticle.
By nature of their ultimate dependency on claim 37, dependent claims 39-45, 47-49, and 57-59 are also rejected because they do not clarify the issues above.
Claim 43 recites the nucleic acid encodes an “ion channel or a protein” which appears to be drawn to two or more options, together with the limitation of “ that is cystic fibrosis transmembrane conductance regulator (CFTR).” The presence of two options in the alternative, together with one singular option that appears to be required, makes it unclear whether or not more options are intended to be encompassed by the claim.
Claim 42 recites “substantially” with no corresponding definition of “substantially.” Therefore the scope of the claim is unclear. A claim may be rendered indefinite by reference to subjective term (see MPEP 2173.05(b), IV). Specifically, the term “substantially” is a subjective term which renders the claim indefinite. The term " substantially " is not defined by the claim, the specification does not provide a standard for some standard for measuring the scope of the term, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention
Withdrawn Claim Rejections – 35 USC § 112(d)
The rejection of claim 57 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 as set forth in the previous office action is withdrawn in view of Applicant’s amendments.
Withdrawn Claim Rejections - 35 USC § 112
Improper Markush
The rejection of claim 43 on the basis that it contains an improper Markush grouping of alternatives as set forth in the previous office action is withdrawn in view of Applicant’s amendments.
Withdrawn Claim Rejections - 35 USC § 103
The rejection of claims 37, 39, 41-45, and 47-50 under 35 U.S.C. 103 as being unpatentable over Levy et al. (Bioorg Med Chem Lett. 2010 Sep 15;20(18):5499-501.; see IDS filed 9th, February, 2021; henceforth “Levy”) in view of Leng et al. (Drug News Perspect. 2007 Mar;20(2):77-86.; henceforth “Leng”), Chamarthy et al. (Mol Immunol. 2003 Dec;40(8):483-90.; henceforth “Chamarthy”) and Heartlein et al. (WO 2015/061467 Al; henceforth “Heartlein”) as set forth in the previous office action is withdrawn in view of Applicant’s amendments.
The rejection of claims 40 and 57 under 35 U.S.C. 103 as being unpatentable over Levy et al. (Bioorg Med Chem Lett. 2010 Sep 15;20(18):5499-501.; see IDS filed 9th, February, 2021; henceforth “Levy”) in view of Leng et al. (Drug News Perspect. 2007 Mar;20(2):77-86.; henceforth “Leng”), Chamarthy et al. (Mol Immunol. 2003 Dec;40(8):483-90.; henceforth “Chamarthy”) and Heartlein et al. (WO 2015/061467 Al; henceforth “Heartlein”), as applied to claim 37 above, and in further view of Megeed et al. (US-20070098702-A1; henceforth “Megeed”) as set forth in the previous office action is withdrawn in view of Applicant’s amendments.
Moot Claim Rejections - 35 USC § 103
The rejection of claim 46 as being unpatentable over Levy et al. (Bioorg Med Chem Lett. 2010 Sep 15;20(18):5499-501.; see IDS filed 9th, February, 2021; henceforth “Levy”) in view of Leng et al. (Drug News Perspect. 2007 Mar;20(2):77-86.; henceforth “Leng”), Chamarthy et al. (Mol Immunol. 2003 Dec;40(8):483-90.; henceforth “Chamarthy”) and Heartlein et al. (WO 2015/061467 Al; henceforth “Heartlein”), as applied to claim 37 above, and in further view of Milla et al. (Curr Drug Metab. 2012 Jan;13(1):105-19.; henceforth “Milla”) as set forth in the previous office action is moot in view of the cancellation of this claim.
The rejection of claim 51 under 35 U.S.C. 103 as being unpatentable over Levy et al. (Bioorg Med Chem Lett. 2010 Sep 15;20(18):5499-501.; see IDS filed 9th, February, 2021; henceforth “Levy”) in view of Leng et al. (Drug News Perspect. 2007 Mar;20(2):77-86.; henceforth “Leng”), Chamarthy et al. (Mol Immunol. 2003 Dec;40(8):483-90.; henceforth “Chamarthy”) and Heartlein et al. (WO 2015/061467 Al; henceforth “Heartlein”) as set forth in the previous office action is moot in view of the cancellation of this claim.
New 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 37, 41-42, 45 and 47-49 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. (Nucleic Acids Res. 2001 Mar 15;29(6):1334-40.; henceforth “Chen”) in view of Levy et al. (Bioorg Med Chem Lett. 2010 Sep 15;20(18):5499-501.; see IDS filed 9th, February, 2021; henceforth “Levy”) and Zalipsky et al. (WO 2011/011631 A2; see IDS filed 7th, May, 2026; henceforth “Zalipsky”).
Regarding claim 37, Chen discloses nanoparticles for transfection of a cell with a nucleic acid, the nanoparticles comprising:
An unnatural 4-branched cationic peptide comprising a lysine (K) core and Histidine (HHK4b; abstract; pg. 1335 col. 1 1st and 3rd para.;; pg. 1336 col. 2; pg. 1337 col. 1-2; pg. 1338 col. 1; Figures 1-8; Discussion); and
Plasmid DNA (abstract; pg. 1355 col. 1 1st and 4th para., col. 2 1st para.; pg. 1337 col. 2 3rd para.; pg. 1338 col. 1 3rd para.; pg. 1339 col. 1 3rd para.; Figures 2, 7-8);
wherein the nucleic acid is associated with the cationic peptides through ionic interactions to form a cationic peptides-nucleic acid core (“polymer-DNA complex” in which “the cationic liposomes neutralize the remainder of DNA charge” pg. 1338 col. 1 3rd para.).
Regarding claim 37, the plasmid DNA disclosed by Chen is “functional for transfection into a cell” as claimed and is also and is also a “functional nucleic acid” as claimed because it was able to be transfected into the cell which is a type of function (see “In vitro transfection studies” pg. 1335)
However, regarding claim 37, Chen is silent to including a hydrophilic polymer bonded to chelators coordinated to metal ions in the nanoparticle.
Nevertheless, regarding claim 37, Levy teaches including the hydrophilic polymer mPEG bonded to the chelator IDA coordinated to a Zn metal ion (mPEG–IDA–Zn) as part of a nanoparticle for delivery of a nucleic acid to a cell that comprises cationic peptides (Title; abstract; pg. 5499-5500; Scheme 1). Levy teaches that grafting mPEG on nanoparticles in addition to Zn-His chelation enhances nanoparticle stability in serum (pg. 5499 col. 2 4th para.).
Therefore, regarding claim 37, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the nanoparticles of Chen, and combine the known prior art element of the mPEG grafting and Zn-His chelation of Levy to obtain the predictable result of a nanoparticle including a hydrophilic polymer bonded to the chelator IDA coordinated to a Zn metal ion. One of ordinary skill would have been motivated to do so as taught by Levy to enhance the nanoparticle stability (pg. 5499 col. 2 4th para.). Regarding the reasonable expectation of success, Levy evidences preparation of nanoparticles comprising cationic peptides including grafting of mPEG and Zn-His chelation (Scheme 1; see also pg. 5499 col. 1 4th para. and pg. 5500 col. 1 1st -4th para.).
Regarding claim 37, Levy teaches coating of the nanoparticle surface with polyethylene glycol (PEG) has the effect of shielding the cationic nature of the particles (pg. 5499 col. 1), and Levy teaches the cationic peptides are grafter to the mPEG-IDA Zn complex (see Figure 4) and therefore the cationic peptides would be expected to coordinate to the Zn ions as part of the complex.
However, regarding claim 37, Chen and Levy are silent to including 2,4-diaminobutyric acid ("Dab") in the branched cationic peptide.
Nevertheless, regarding claim 37, Zalipsky teaches nanoparticles for transfection of a cell with a nucleic acid (“a stable nanoparticle for nucleic acid delivery to cells and tissues” abstract see also “nucleic acid containing nanoparticle, also referred to herein as a nanoplex (NPX)” para. [0004]), the nanoparticles comprising 4-branched cationic peptides comprising a lysine core and Histidine (H) (see in particular d) through i) of claims 29-30). Zalipsky teaches the nanoparticles comprise a nucleic acid (para. [0004-0006, 0025-0029, 0031-0040, 0052-0053, 0056-0058]; claims 1-14, 16-17, 34-35, 43, 49-52) that is DNA (para. [0006] numbered paragraph 2; claim 2) or a functional nucleic acid (“functional nucleic acids” para. [0004]) that is functional for transfection into a cell. Zalipsky teaches the nucleic acid is associated with the cationic peptides in a non-covalent complex (para. [0006] numbered paragraph 1, 37, 47-49; para. [0037, 0056]; claims 1, 39, 49-51). Zalipsky teaches a hydrophilic polymer (para. [0006] numbered paragraphs 1, 18-19, 23, 28-29, 33, 47; para. [0026, 0040, 0046, 0049, 0056]; claims 1, 18-19, 25, 30-31, 35 and 49), and Zalipsky teaches mPEG as a specific preferred embodiment of a hydrophilic polymer (para. [0006] numbered paragraph 33, 35-37, 48-49; para. [0007-0011, 0013-0014, 0016, 0021-0022, 0041, 0062-0068, 0071, 0073-0074, 0077, 0079, 0082-0083, 0085-0090, 0093, 0095]; Examples 1-5, 7-8; claims 35, 37-39, 50-51; Figures 3-4 and 11) as part of the nanoparticle. Zalipsky teaches for the branched cationic polymers, one or more lysines are replaced by an amino acid selected from the group consisting of: 2,5-diaminopentanoic acid, 2,4-diaminobutanoic acid and 2,3-diaminopropionic acid (claim 29; see also paragraph 27 pg. 8; para. [0038]).
Therefore, regarding claim 37, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the nanoparticles as suggested by Chen in view of Levy, and simply substitute one or more of the lysines in the branched cationic peptide of Chen with the 2,3-diaminopropionic acid of Zalipsky to obtain the predictable result of a branched cationic peptide for use in a nanoparticle for the transfection of a cell. One of ordinary skill would have been motivated to do so as taught by Zalipsky because Zalipsky teaches 2,3-diaminopropionic acid as a known alternative option for lysine residues as part of a branched cationic peptide (claim 29; see also paragraph 27 pg. 8; para. [0038]). Regarding the reasonable expectation of success, Zalipsky teaches preparation of nanoparticles including branched cationic peptides that include 2,3-diaminopropionic acid (claim 29; see also paragraph 27 pg. 8; para. [0038]).
Furthermore, regarding the wherein clauses “the nucleic acid is associated with the cationic peptides through ionic interactions to form a cationic peptides-nucleic acid core” and “the hydrophilic polymer forms a protective layer around the cationic peptides-nucleic acid core through coordination of cationic peptides to metal ions” of claim 37, this recites the result of the presence of the claimed structures (nucleic acids and cationic peptides) present together, and therefore is met by the nanoparticles as suggested above which meets all the structural requirements of instant claims (See MPEP 2111.04 regarding wherein clauses).
Regarding claim 41, further to the discussion of claim 37 above, Levy teaches a 50:1 molar ratio of the hydrophilic polymer bonded to chelators coordinated to metal ions and the cationic peptides, and Levy teaches the molar ratio was varied to obtain different degrees of PEG grafting (pg. 5500). Therefore, it would be obvious to use the 50:1 molar ratio of Levy when combing the hydrophilic polymer mPEG bonded to the chelator IDA coordinated to a Zn metal ion (mPEG–IDA–Zn) for the reasons suggested above.
Regarding claim 41, the 50:1 molar ratio suggested by overlaps with the claimed range of greater than 50:1 and thereby makes it obvious. Furthermore, because Levy teaches varying the molar ratio to obtain different degrees of PEG grafting (pg. 5500), one of ordinary skill would have been motivated by routine experimentation to optimize the molar ratio to obtain different degrees of PEG grafting with a reasonable expectation of success as taught and evidence by Levy (pg. 5500).
Notably, regarding claim 41, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists and It is routine procedure to optimize component amounts to arrive at an optimal product that is superior for its intended use. See M.P.E.P. §2144.05.
Regarding claim 42, further to the discussion of claim 37 above, Levy teaches the hydrophilic polymer stabilizes nanoparticles that include a nucleic acid, cationic peptides, and a hydrophilic polymer bonded to chelators coordinated to metal ions as demonstrated by resistance to agglomeration in a high ionic strength environment (100 mM sodium chloride), wherein substantially no aggregation in 100 mM NaCl occurs for 40 minutes (50:1 molar ration; figure 3; pg. 5500).
However, regarding claim 42, Chen, Levy, and Zalipsky are silent to whether there is substantiality no aggregation in 50 mM NaCl for 3 hours.
Nevertheless, regarding claim 42, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention that the nanoparticles as suggested by Chen in view of Levy and Zalipsky would have the property of substantiality no aggregation in 50 mM NaCl for 3 hours because the nanoparticles of Levy, which that include a nucleic acid, cationic peptides, and a hydrophilic polymer bonded to chelators coordinated to metal ions, show no aggregation over time in 100 mM NaCl, which is an even higher ionic strength environment, for up to 40 minutes, with no indication of a change in aggregation over time (i.e. there is not a relationship between time and aggregation amount) It would therefore, be obvious that under a lower ionic strength environment, the aggregation would also not change out to 3 hours and this appears to be an expected property of the claimed combination.
Furthermore, regarding claim 42, as set forth above, Chen, Levy and Zalipsky teach the structural requirements of instant claims and therefore the claimed functional properties of substantially no aggregation in 50 mM NaCl for 3 hours would also naturally follow the preparation of the taught structure.
Regarding claim 45, further to the discussion of claim 37 above, Chen teaches the nanoparticles have an average diameter of about 50 nm (see Figure 4).
Regarding claim 47, further to the discussion of claim 37 above, as stated above (see claim 37 rejection above), the chelator taught and suggested by Levy above is IDA (Title; abstract; pg. 5499-5500; Scheme 1).
Regarding claim 48, further to the discussion of claim 37 above, as stated above (see claim 37 rejection above), the metal ions taught and suggested by Levy above are Zn2+ (Title; abstract; pg. 5499-5500; Scheme 1).
Regarding claim 49, further to the discussion of claim 37 above, as stated above (see claim 37 rejection above), Levy teaches and suggests the hydrophilic polymer is mPEG bonded to iminodiacetic acid (IDA) which is coordinated to Zn2+ (mPEG–IDA–Zn; Title; abstract; pg. 5499-5500; Scheme 1).
Hence, the claimed invention as a whole was prima facie obvious.
Claims 39 and 43-44 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. (Nucleic Acids Res. 2001 Mar 15;29(6):1334-40.; henceforth “Chen”) in view of Levy et al. (Bioorg Med Chem Lett. 2010 Sep 15;20(18):5499-501.; see IDS filed 9th, February, 2021; henceforth “Levy”) and Zalipsky et al. (WO 2011/011631 A2; see IDS filed 7th, May, 2026; henceforth “Zalipsky”) as applied to claim 37 above, and in further view of Heartlein et al. (WO 2015/061467 Al; henceforth “Heartlein”).
The teachings of Chen, Levy, and Zalipsky above are incorporated herein in their entirety.
Regarding claim 39, further to the discussion of claim 37 above, Chen, Levy, and Zalipsky are silent to providing the nanoparticles in a physiologically acceptable buffer of saline (pg. 5500).
Nevertheless, regarding claim 39, Heartlein teaches nanoparticles in a physiologically acceptable buffer (i.e. pharmaceutical compositions with suitable excipients; para. [0416]), including a Saline aerosol (para. [0476]).
Therefore, regarding claim 39, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the nanoparticles as suggested by Chen in view of Levy and Zalipsky and combine the known prior art element of the physiologically acceptable buffer Saline aerosol of Heartlein to obtain the predictable result of physiologically acceptable nanoparticles. One of ordinary skill would have been motivated to do so as taught by Heartlein so that the nanoparticles could be delivered via local administration to a subject to allow the compositions to diffuse from the site of implantation to surrounding cells to provide protein replacement therapy (para. [0420, 0463]). Regarding the reasonable expectation of success, Heartlein evidences nanoparticles in a saline aerosol physiologically acceptable buffer (i.e. pharmaceutical compositions with suitable excipients; para. [0416]), including a Saline aerosol (para. [0476]).
Regarding claim 43, further to the discussion of claim 37 above, although Chen teaches the nanoparticle comprises plasmid DNA that encodes a protein (Luciferase), Chen, Levy and Zalipsky are silent to including plasmid DNA that encodes CFTR.
Nevertheless, regarding claim 43, Heartlein teaches nanoparticles for the delivery of a functional nucleic acid (cDNA) (abstract; Background; Examples 3-6; para. [0037, 0376 0463]; Figure 14) that encodes the CFTR proteins to treat the deficiency of CFTR protein in cystic fibrosis (background; Example 5; para. [0037, 0463]).
Therefore, regarding claim 43, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the nanoparticles as suggested Chen in view of Levy and Zalipsky, and substitute the CFTR DNA for the Luciferase DNA in the Plasmid of Chen to obtain the predicable result of a nanoparticle for transfection of a cell with nucleic acid. One of ordinary skill would have been motivated to do so as taught Heartlein to treat the deficiency of CFTR protein in cystic fibrosis (background; Example 5; para. [0037, 0463]). Regarding the reasonable expectation of success, Chen evidences preparation of a nanoparticle comprising plasmid DNA encoding luciferase and therefore one of ordinary skill would have a reasonable expectation of success in preparing the nanoparticle with a plasmid DNA encoding CFTR.
Regarding claim 44, further to the discussion of claim 37 above, Chen, Levy and Zalipsky are silent to adaptation for topical delivery on an mucus membrane.
Nevertheless, regarding claim 44, Heartlein teaches topical delivery on an mucous membrane (aerosol delivery/ intratracheal administered, intrabronchial or intranasal) of nanoparticles to the lung (Examples 5-6; para. [0016, 0418-0419, 0463-0478]).
Therefore, regarding claim 44, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the nanoparticles as suggested by Chen, Levy and Zalipsky and combine the known prior art element of adapting them for aerosol delivery to obtain the predictable result of nanoparticles for topical delivery. One of ordinary skill would have been motivated to do so as taught by Heartlein because aerosol delivery effectively caused expression of CFTR in the target site, the lungs, in an animal model (para. [0472]). Regarding the reasonable expectation of success, Heartlein evidences topical delivery on an mucus membrane (aerosol delivery/ intratracheal administered, intrabronchial or intranasal) of nanoparticles to the lung (Examples 5-6; para. [0016, 0418-0419, 0463-0478]).
Hence, the claimed invention as whole was prima facie obvious.
Claims 40 and 57 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. (Nucleic Acids Res. 2001 Mar 15;29(6):1334-40.; henceforth “Chen”) in view of Levy et al. (Bioorg Med Chem Lett. 2010 Sep 15;20(18):5499-501.; see IDS filed 9th, February, 2021; henceforth “Levy”) and Zalipsky et al. (WO 2011/011631 A2; see IDS filed 7th, May, 2026; henceforth “Zalipsky”) as applied to claim 37 above, and in further view of Megeed et al. (US-20070098702-A1; henceforth “Megeed”).
The teachings of Chen, Levy, and Zalipsky above are incorporated herein in their entirety.
Regarding claim 40, further to the discussion of claim 37 above, Chen, Levy and Zalipsky are silent to whether the cationic peptide to nucleic acid ratio is charge:charge balanced with a ratio between 1:1.4 and 1:1.6.
Nevertheless, regarding claim 40, Megeed teaches a charge: charge balanced cationic peptide to nucleic acid ratio which is a 1:1 ratio (nanoparticle including a cationic peptide fully neutralized net negative charges of pDNA; para. [0131]) to help overcome stability issues of nucleic acids in physiological conditions (para. [0135]).
Therefore, regarding claim 40, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the nanoparticles as suggested by Chen in view of Levy and Zalipsky, and combine the known prior art element of the charge:charge balanced cationic peptide to nucleic acid ratio of Megeed to obtain the predictable result of a stable nucleic acid in physiological conditions. One of ordinary skill would have been motivated to do so as taught by Megeed to decrease the columbic repulsions between nucleic acid phosphates and to promote hydrophobic interactions at the complexed sites, which would help overcome stability issues of nucleic acids in physiological conditions (para. [0135]). Regarding the reasonable expectation of success, Megeed evidences charge: charge balanced cationic peptide to nucleic acid ratios in nanoparticles (nanoparticle including a cationic peptide fully neutralized net negative charges of pDNA; para. [0131]).
Regarding claim 40, Applicant is directed to MPEP section 2144.05 which states a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985) (Court held as proper a rejection of a claim directed to an alloy of "having 0.8% nickel, 0.3% molybdenum, up to 0.1% iron, balance titanium" as obvious over a reference disclosing alloys of 0.75% nickel, 0.25% molybdenum, balance titanium and 0.94% nickel, 0.31% molybdenum, balance titanium. "The proportions are so close that prima facie one skilled in the art would have expected them to have the same properties."). In the instant case, the charge: charge balanced ratio of 1:1 suggested by Megeed is so close to the 1:1.4 ratio of the instantly claimed range that prima facie one skilled in the art would have expected them to have the same properties.
Regarding claim 57, further to the discussion of claim 37 above, Chen, Levy and Zalipsky are silent to the cationic peptides further comprising arginine.
Nevertheless, regarding claim 57, Megeed teaches nanoparticles comprising Histidine and Lysine as well as arginine (see “(KHKHKHKHKK),(RHRHKHC), (KHKHCKK), and (KGKHGRC)” para [0053], see also “copolymers of lysine-arginine-histidine” para. [0055]; see also para. [0032, 0041, 0053-0055, 0065]; claims 2-4, 2629, 39]) for the transfection of a cell to optimize the cationic amino acids depending on the on the size of the therapeutic gene or oligonucleotide being delivered and its ability to bind to the amino acids (para. [0057]).
Therefore, regarding claim 57, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the nanoparticles as suggested by Chen in view of Levy and Zalipsky and combine the known prior art element of the including arginine residues in the peptide of Megeed to obtain the predictable results of a nanoparticle for transfecting DNA into a cell (see MPEP 2143 Exemplary Rationale (B)). One of ordinary skill would have been motivated to do so as taught by Megeed to optimize the cationic amino acids depending on the on the size of the therapeutic gene or oligonucleotide being delivered and its ability to bind to the amino acids (para. [0057]). Regarding the reasonable expectation of success, Megeed evidences nanoparticles with comprising Histidine and Lysine as well as arginine (see “(KHKHKHKHKK),(RHRHKHC), (KHKHCKK), and (KGKHGRC)” para [0053], see also “copolymers of lysine-arginine-histidine” para. [0055]; see also para. [0032, 0041, 0053-0055, 0065]; claims 2-4, 2629, 39]) for the transfection of a cell.
Hence, the claimed invention as whole was prima facie obvious.
Claims 43 and 59 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. (Nucleic Acids Res. 2001 Mar 15;29(6):1334-40.; henceforth “Chen”) in view of Levy et al. (Bioorg Med Chem Lett. 2010 Sep 15;20(18):5499-501.; see IDS filed 9th, February, 2021; henceforth “Levy”) and Zalipsky et al. (WO 2011/011631 A2; see IDS filed 7th, May, 2026; henceforth “Zalipsky”) as applied to claim 37 above, and in further view of Divita et al. (WO-2017/205846-A1; henceforth “Divita”).
The teachings of Chen, Levy, and Zalipsky above are incorporated herein in their entirety.
Regarding claims 43 and 59, further to the discussion of claim 37 above, although Chen teaches the nanoparticle comprises plasmid DNA that encodes a protein (Luciferase), Chen, Levy and Zalipsky are silent to including plasmid DNA that encodes CFTR (instant claim 43) or A1AT (instant claim 59).
Nevertheless, regarding claims 43 and 59, Divita teaches nanoparticles for transfection of a cell that comprise plasmid DNA that encodes template DNA corresponding to WT DNA sequences (para. [0209, 0282-0289]) and Divita teaches target genes of A1AT to treat liver disease of alpha 1-antitrypsin Deficiency (para. [0269, 0291]) or CFTR to treat lung disease of fibrosis (para. [0270-0271, 0291]).
Therefore, regarding claims 43 and 59, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the nanoparticles suggested by Chen in view of Levy and Zalipsky and simply substitute the known prior art elements of the template DNA encoding CFTR (instant claim 43) or A1AT (instant claim 59) of Divita for the DNA that encodes luciferase in the plasmid of Chen to obtain the predictable result of a nanoparticle for transfection of a cell with nucleic acid. One of ordinary skill would have been motivated to do so as taught by Divita so that the nanoparticles could be used to treat the liver disease of alpha 1-antitrypsin Deficiency (para. [0269, 0291]) or to treat the lung disease of fibrosis (para. [0270-0271, 0291]). Regarding the reasonable expectation of success, Chen evidences preparation of a nanoparticle comprising plasmid DNA encoding luciferase and therefore one of ordinary skill would have a reasonable expectation of success in preparing the nanoparticle with a plasmid DNA encoding CFTR of A1AT.
Hence, the claimed invention as whole was prima facie obvious.
Examiner’s Remark
It is noted that claim 58 was previously indicated as free of the prior art. In the amendment filed 9th, March 2026, new limitations of the branched sequences 90% identical to (i), (ii), (iii), (iv), (v), (vi) and (vii), that had not previously been considered were added to claim 58 and are considered specifically for the first time in this office action.
Amended claim 58 is free of the prior art. However, claim 58 is not allowable because it is rejected under 35 U.S.C. 112a above, and it is dependent on rejected claim 37.
Conclusion
No claim is allowable.
Correspondence
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/BRIANA N EBBINGHAUS/Examiner, Art Unit 1632
/EMILY A CORDAS/Primary Examiner, Art Unit 1632
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