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, 39-49 and 51-58 are pending.
Claims 52-56 are withdrawn.
Claims 37, 39-49, 51 and 57-58 are under examination.
Examiner’s Remark
Applicant has noted that claim 50 was recited in rejections in the previous Office Action and has requested clarification since claim 50 was cancelled in the previously set forth amendment filed on 24th, February, 2025. The Examiner notes that because claim 50 was cancelled in the previously set forth amendment filed on 24th, February, 2025, all previously set forth rejections over claim 50 have been withdrawn in view of the cancellation of the claim.
Claim Objections
Claim 57 is objected to because of the following informalities:
Claim 57 recites “further comprise arginine up to 20 arginine residues.” Which does not have a conjunction or linking phrase between “arginine” and “up to 20 arginine.” While it is clear that the peptide further comprises at least one arginine residue and may comprise up to 20 arginine residues, it would be more clear if written as “the cationic peptides further comprise 1 to 20 arginine residues in length attached to the lysine core.”
Appropriate correction is required.
Withdrawn Claim Rejections – 35 USC § 112(a)
Written Description
The rejection of claim 50 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paragraph, as failing to comply with the written description requirement as set forth in the previous office action is withdrawn in view of the cancellation of this claim in the previously set forth amendment filed on 24th, February, 2025.
New 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.
In the amendment filed on 4th, September, 2025 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.
Independent claim 37
“6-, or 8-branched cationic peptides”
The closest support the limitation of “6-branched cationic peptides” is the recitation of “5 branches or more” (para. [0065]). There is one specific recitation of an 8-branched cationic peptide (Figure 11 “H3K8b(+RGD)”)
The closest support the limitation of “8-branched cationic peptides” is the recitation of a single specific “8-branched cationic peptide” (“8 branched H3K8b(+RGD)” para. [0055] and Figure 11), as well as a recitation of “5 branches or more” (para. [0065]). The recitation of a single specific 8-branched cationic peptide does not provide support for the full breadth of the structurally and functionally diverse genus of cationic peptides encompasses by instant claims.
Furthermore the recitation of “5 branches or more” (para. [0065]) does not provide support for “6- or 8-branched cationic peptides” because these limitations recite a specific point after the broader original disclosure of “5 branches or more.” As noted by MPEP 606.03(o), 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 (see also MPEP 2163.05 (III) Range Limitations).
“2,3-diaminobutyric acid”
The closest support for this limitation is recitations of “2,4- diaminobutyric acid” (para. [0007, 0009-0011, 0018, 0024, 0044, 0064]) which is a structurally distinct amino acid with different properties and does not provide support for the claimed “2,3-diaminobutyric acid.”
“no other amino acids”
This limitation recites a negative limitation. There is no specific or explicit recitation of this limitation and therefore there is no basis for this limitation in the original disclosure. Furthermore, this limitation excludes all other amino acids from the structure, and not all amino acids have been specifically recited in the instant application as originally filed. Applicant is directed to MPEP section 2173.05(i) which states any negative limitation or exclusionary proviso must have basis in the original disclosure. As stated above, this negative limitation was not found to have basis in the original disclosure.
“the number of lysine residues comprising the lysine core is sufficient to present an appropriate number of amino groups suitable to accommodate 2, 4, 6, or 8 branches off of the lysine core”
As stated above, there is insufficient support for 6- or 8- branched cationic peptides and therefore accommodating 6, or 8 branches off of the lysine core also does not have support in the originally filed disclosure for the reasons stated above.
The closest support for numbers of lysine residues in the lysine core is recitation of “the 3-lysine core” (para. [0055]; figure 11) which includes 3 lysine residues, as well as specific sequences and branched sequences recited in Table 1 (para. [0025]). Therefore, the instant specification only provides support for 3 lysine residues while the limitation in question allows for all possible numbers of lysine residues in the core that 2, 4, 6, or 8 branches off of the lysine core which encompasses cores with all possible numbers of lysine residues of more than 3. The disclosure of one species of 3 residues does not provide support for such a vast genus.
“each of 2,3- diaminopropionic acid, 2,4-diaminobutyric acid, 2,3-diaminobutyric acid, and ornithine may contain all R stereocenters, all S stereocenters; or mixtures of R and S stereocenters”
As stated above, there is not support for 2,4-diaminobutyric acid in the originally filed disclosure and therefore the recitation of “all R stereocenters, all S stereocenters; or mixtures of R and S stereocenters” with respect to this amino acid is also not supported.
Regarding the limitation with respect to 2,3- diaminopropionic acid, 2,3-diaminobutyric acid, and ornithine containing all R stereocenters, all S stereocenters; or mixtures of R and S stereocenters, the closest support for this limitation is the recitation of the amino acids 2,3- diaminopropionic acid, 2,3-diaminobutyric acid, and ornithine (para. [0009]). The instant specification is silent to specific recitations of stereocenters of the amino acids or combinations of stereocenters. Because it is well known in the art that the specific stereocenters are structurally distinct with functionally distinct properties, the broad disclosure of the amino acids 2,3- diaminopropionic acid, 2,3-diaminobutyric acid, and ornithine cannot provide support for the specific recitations of specific stereocenters and combinations of stereocenters in these residues as parts of the claimed branched cationic peptides and further it cannot provide support for all possible combinations encompassed by instant claims comprising all possible combinations of the stereocenter combinations, which are structurally and functionally distinct embodiments.
“wherein the peptide has a maximum length of about 150 amino acids and a minimum length of about 50 amino acids”
The closest support for this limitation is the specific disclosure of species of cationic peptides recited in Table 1 (para. [0025]). The recitation of 12 specific branched amino acids does not provide support for the vast genus of structurally and functionally distinct amino acids from about 50 to 150 amino acids.
Importantly, as a whole, amended claim 37 requires the following limitations for the cationic peptides includes the new limitations discussed above,
“2-, 4-, 6-, or 8-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, 2,4-diaminobutyric acid, 2,3-diaminobutyric acid, and ornithine and no other amino acids; wherein the number of lysine residues comprising the lysine core is sufficient to present an appropriate number of amino groups suitable to accommodate 2, 4, 6, or 8 branches off of the lysine core; and wherein each of 2,3-diaminopropionic acid, 2,4-diaminobutyric acid, 2,3-diaminobutyric acid, and ornithine may contain all R stereocenters, all S stereocenters; or mixtures of Rand S stereocenters” and “wherein the peptide has a maximum length of about 150 amino acids and a minimum length of about 50 amino acids.”
The instant specification discloses only 1 specific 4 branched-cationic peptides, labeled “X” (Table 1 pg. 6), that meet all the claimed structural criteria. 1 specific species is not representative of the vast and structurally and functionally diverse genus of cationic peptides encompassed by instant claims and therefore these amendments appear to be new matter.
Dependent Claims
“glycine” (instant claim 39) as a physiologically acceptable buffer
There is no disclosure of “glycine” in the instant specification. The closest support for this limitation is the general disclosure of “physiologically acceptable buffer” and the specific disclosure of structurally distinct physiologically acceptable buffers off “PBS, HEPES, saline, lactated ringers, ultrapure water, and the like” (para. [0036]). The general disclosure of “physiologically acceptable buffer” does not provide sufficient support of one very specific species of glycine that is not otherwise recited and the disclosure of structurally distinct buffers not provide sufficient support of one very specific species that is structurally distinct.
“between 1 :1.2 and 1 :1.6” (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 :1.6” (see MPEP 2163.05 (III) Range Limitations).
the molar ratio of the hydrophilic polymer bonded to chelators coordinated to metal ions and the cationic peptides is greater than “28:1” (instant claim 41)
There is no specific disclosure of “greater than 28:1. ” The closest support of the range of “greater than 28:1” is the previously claimed “great than 50:1” ratio which is supported by original claim 5. The recitation of a narrower range “great than 50:1” does not provide support for the broader claimed range of “greater than 28:1” (see MPEP 2163.05 (III) Range Limitations).
“Hanks Balanced Salt Solution and SAGM media for at least 7 days at room temperature or at 37° C” (instant claim 42).
There is no specific recitation of “Hanks Balanced Salt Solution” and “SAGM media” in the originally filed disclosure. The closest support for these limitations is the broad disclosure of “cell culture media” (para. [0083, 0047, 0077, 0080, 0083]) and the broad disclosure of “solution” (para. [0030-0032, 0086]), as well as specific solutions such as PBS or NaCl solutions (para. [0077] and 50 mM NaCl para. [0011, 0068]). The broad disclosure of cell culture medias and solutions does not provide support for the two very specific solutions recited and further the disclosure of other distinct solutions also does not provide support for these two specific solutions.
Regarding the limitation of “for at least 7 days” there is no specific recitation of this limitation. The closest support for this limitation is “preventing aggregation in 50 mM NaCl for at least 3 hours” (para. [0011]; see also para. [0068]). The disclosure of the broader range of “at least 3 hours” does not provide support for the narrower range of “at least 7 days” (see MPEP 2163.05 (III) Range Limitations).
Regarding the limitation of “at room temperature or at 37° C there is no recitation of these limitations in the original disclosure. The closest support for this limitation is “preventing aggregation in 50 mM NaCl for at least 3 hours” (para. [0011]; see also para. [0068]) which does not recite a specific temperature and therefore there is not support for the specifically recited temperatures.
“up to 20 arginine residues in length attached to the lysine core” (instant claim 57)
There is no specific disclosure of “up to 20 arginine residues in length attached to the lysine core” which is a range of 0-20 additional arginine in the core. The closest support for this limitation is the general disclosure that arginine can be included in the peptide (para. [0024, 0044, 0065]). The general disclosure that arginine can be included does not provide sufficient support for the numerous distinct peptides encompasses by the range of “up to 20 arginine residues.” (see MPEP 2163.05 (III) Range Limitations).
“(ii) (H-Orn-His-Orn-His-His-Orn-His-His-Orn-His-His-Orn-His-His-Orn-His-His-Orn-His-Orn)4-Lys-Lys-Lys-His-His-His-His-Asn-His-His-His-His- Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-OH;
(iii) (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-ArgArg-Arg-OH; and
(iv) (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” (dependent claim 58)
There is not support for these specific branched cationic peptides in the disclosure. The closest support is disclosure of 12 structurally and functionally distinct cationic peptides that do not provide support for these 3 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 from the general disclosure of cationic peptides
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 4th, September, 2025, have been fully considered but are not found persuasive.
Applicant argues “Support for the amendments to the claims is provided by the specification. All of the detailed alternatives and ranges recited in the claims are set forth clearly in the specification” (pg. 8).
In response, as stated 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."). 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)).
Applicant argues “ With respect to the non-canonical amino acids disclosed in the claims, the specification, at paragraph [0090], discloses amino acid analogs, which would be clearly understood by one skilled in the art as including 2,3-diaminobutyric acid in view of the disclosure of the analogs and homologs 2,4-diaminobutyric acid and 2,3-diaminopropionic acid” (pg. 8).
In response, there is no para [0090] of the specification. It is believed this is s a typographical error for para. [0009], which only discloses the specific amino acid analogs of 2,3-diaminopropionic acid,
2,4-diaminobutyric acid, ornithine and does not provide guidance or information that would lead one of ordinary skill to conclude that other amino acid analogs were supported as amino acid analogs are structurally and functionally distinct and further as there are hundreds of possible amino acids and amino acid analogs that could have distinct structural and functional consequences if included in the instantly claimed cationic peptides as part of a nanoparticle.
Applicant further argues “Similarly, branched peptides are also disclosed in that paragraph. The structures disclosed clearly include a core of amino acid residues that are positively charged at physiological pH values” (pg. 8).
In response, as stated above there is no para [0090] of the specification and therefore it is believed this is s a typographical error for para. [0009]. Further, as discussed above, specific species of core structures are disclosed in Table 1 which do not provide support for the full breadth of structurally and functionally distinct cationic peptides encompassed by Applicants claims as amended.
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.
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 genus is:
Nanoparticles comprising 2-, 4-, 6-, or 8-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, 2,4-diaminobutyric acid, 2,3-diaminobutyric acid, and ornithine and no other amino acids; wherein the number of lysine residues comprising the lysine core is sufficient to present an appropriate number of amino groups suitable to accommodate 2, 4, 6, or 8 branches off of the lysine core; and wherein each of 2,3- diaminopropionic acid, 2,4-diaminobutyric acid, 2,3-diaminobutyric acid, and ornithine may contain all R stereocenters, all S stereocenters; or mixtures of R and S stereocenters
wherein the peptide has a maximum length of about 150 amino acids and a minimum length of about 50 amino acids.
The broadest reasonable interpretation of the scope of this genus encompasses an unfathomably large number of structurally and functionally distinct cationic peptides for the reasons stated below.
As stated above, the cationic peptide has a maximum length of about 150 amino acids and a minimum length of about 50 amino acids. For each of the first 50 amino acids (the minimum length), each position can be one of histidine and 2,3-diaminopropionic acid, 2,4-diaminobutyric acid, 2,3-diaminobutyric acid, and ornithine, which is five total options, for each spot. This means that for an 50 amino acids length, there are 550 structurally distinct options. Since instant claims require at least two of the amino acid types, there are 550 -5 (subtract the five sequences that are all of one type) structurally distinct options which is an unfathomably large genus of structurally distinct sequences which applies only to the minimum 50 amino acids length. If the lysine core is includes in the length, this estimate is 550-3 -5= 547 -5 sequences to account for at least 3 lysine residues of the core.
Furthermore, the 547 -5 number of sequences is a gross underestimation for the reasons stated below.
Instant claims encompass up to a maximum length of about 150 amino acids and therefore each of the spots after the first 50 amino acids can be 6 options (each of the five options of amino acids of no amino acid since that spot is empty) which adds an additional 6100 sequence options for each of the already distinct 547 -5 sequences. Amounting to a total estimate of 547 -5 + 6100 sequences.
Additionally, the amino acids are branched 2-, 4-, 6-, or 8-branched cationic peptides which encompasses distinct structures off all possible branch lengths and combinations of the already unfathomable number of sequences above.
Furthermore, instant claims allow for each of 2,3- diaminopropionic acid, 2,4-diaminobutyric acid, 2,3-diaminobutyric acid, and ornithine may contain all R stereocenters, all S stereocenters; or mixtures of Rand S stereocenters. 2,3- diaminopropionic acid, 2,4-diaminobutyric acid, and ornithine have one stereocenter. This means that for each time 2,3- diaminopropionic acid, 2,4-diaminobutyric acid, and ornithine occur in the already unfathomable number of sequences above, there are two structurally distinct options for that spot. 2,3-diaminobutyric acid has two stereocenters. This means that for each possible spot 3-diaminobutyric acid occurs in the already unfathomable number of sequences above, there are four (RR, RS, SS, SR) structurally distinct options for that spot.
Revisiting the estimate above, which is already a gross underestimate for the reasons stated above, this now allows for 1447 -5 sequences to account for the first 50 amino acids, and 1447 -5 + 15100 to account for the possible sequences from 50 to 150 amino acids. 1447 -5 + 15100 sequences is clearly an unfathomably large number of structurally distinct sequences.
Disclosure of Structure
Regarding the branched cationic peptides, Applicant discloses 1 specific 4 branched-cationic peptides, labeled “X,” (Table 1 pg. 6), that has a core that comprises 3 lysine residues, that meets the criteria as claimed.
There is no disclosure of specific stereocenters or combinations of stereocenters for any branched cationic peptide.
There is no disclosure of 2-, 6- or 8-branched cationic peptides that meet the criteria as claimed.
There is no disclosure of other sequences lengths.
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.
Regarding stereocenters, it is well known in the art that molecules with different combinations of stereocenters can have distinct functional properties, and therefore the combinations of stereocenters contemplated cannot be expected to have predictable functional properties.
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 insufficient description of the branches cationic peptides as claimed. Specifically, Applicant discloses 1 species examples of the claimed branched cationic peptide. 1 species examples is not representative of such a diverse genus that encompasses an unfathomable number of structurally and functionally distinct peptides.
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, and Applicant has not shown possession of the invention.
Response to Arguments
Applicant’s amendments necessitated the changes to the grounds of rejection above.
Applicant’s arguments, filed 4th, September, 2025, have been fully considered but are not found persuasive.
Applicant argues that the “the compositions recited in the specification, including the peptides, provide sufficient description of their structure, including specific amino acid sequences and the occurrence of non-canonical amino acids, to comply with the written description requirement” (pg. 15-16).
Applicant argues “amended, claim 37 describes the peptides incorporated into the nanoparticles in sufficient detail, including the details of branching, the size of the peptides, and the amino acid composition of the peptides, including noncanonical amino acids, to meet the requirements of the written description requirement of 35 U.S.C. § 112(a)” (pg. 18).
In response, the amended claims do not meet the written description requirement of 35 U.S.C. § 112(a) for the reasons stated above. In brief, the amended claims encompass a vast number of structurally and functionally distinct sequences while the instant specification discloses 3 specific species that meet the structural requirements. 3 specific species is not representative of the vast and diverse genus of cationic peptides encompassed by Applicant’s claims.
Applicant argues “peptide sequences such as those described in the specification and recited in the claims, including the occurrence of non-canonical amino acids, are actually chemical materials and need to be treated as such in a determination of compliance with the written description requirement. The description need only describe in detail that which is new or not conventional. Hybritech, Inc. v. Monoclonal Antibodies, Inc., 231 U.S.P.Q. 81 (Fed. Cir. 1986). Further detail with respect to the sequences of the genes to be transfected and with respect to the peptides in the compositions is therefore not required.” (pg. 16).
In response, “the sequences of the genes to be transfected” is no longer an issue in the amended claims. Regarding “peptides in the compositions,” Applicant has not shown possession of the genus of branched cationic peptides for the reasons stated above. In brief, the amended claims encompass a vast number of structurally and functionally distinct sequences while the instant specification discloses 3 specific species that meet the structural requirements. 3 specific species is not representative of the vast and diverse genus of cationic peptides encompassed by Applicant’s claims. Further, while Applicant states the peptide sequences are chemical materials, no formula is claimed that would represent an adequate description of the claimed genus.
Applicant argues “The decision in Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559 (Fed. Cir. 1997), cert. denied, 523 U.S. 1089 (1998) clearly supports the compliance of these claims with the written description requirement” (pg. 17). Applicant argues “one skilled in the art can distinguish such a formula from others and can identify many of the species that the claims encompass. Accordingly, such a formula is normally an adequate description of the claimed genus. In the present application, such structural features are provided in the specification (and recited in the claims). These features include the specific structures of the nucleic acid-binding peptides” (pg. 17).
In response, while Applicant recites a formula, there is no specific formula claimed. The structural features recited in the claims are not sufficient to meet the written description requirement for the reasons stated above.
Withdrawn Claim Rejections - 35 USC § 112(b)
The rejection of claims 43 and 35 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.
New 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 42-43 and 57 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 42 contains the trademark/trade name “SAGM”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe cell culture media and, accordingly, the identification/description is indefinite.
Because this reagent was developed by the manufacturer at the time of the applicant’s invention under the trade name SAGM and as a result is proprietary, which means what constitutes as a SAGM can change, and these changes do not need to be disclosed by these companies to the public. Accordingly, the identification of the trade name is indefinite and the applicant is advised to employ a sequence, the SeqID, IUPAC name and/or CAS number for this agent.
Claim 43 recites “the nucleic acid encodes an enzyme, a receptor, an ion channel or a protein selected from cystic fibrosis transmembrane conductance regulator (CFTR) and A1AT.” The scope of the claim is unclear because while the option of CFTR is a protein and an ion channel, it is not an enzyme or a receptor. Similarly while the option of A1AT is a protein, it is not an enzyme, a receptor, an ion channel. Therefore, it is unclear what the scope of the claim encompasses because none of options listed in the Markush are enzymes or receptors.
Claim 57 recites “the cationic peptides further comprise arginine up to 20 arginine residues in length attached to the lysine core.” However, claim 37, upon which claim 57 depends, already recites that the cationic peptides comprise “no other amino acids.” It is unclear how the cationic peptides can comprise additional arginine residues while still meeting the limitation of comprising “no other amino acids,” and therefore the metes and the bounds of the claim are unclear and it is also unclear how claim 57 can further limit claim 37.
Claim Rejections – 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection I, a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 57 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 57 recites “the cationic peptides further comprise arginine up to 20 arginine residues in length attached to the lysine core.” However, claim 37, upon which claim 57 depends, already recites that the cationic peptides comprise “no other amino acids.” Because “the cationic peptides further comprise arginine up to 20 arginine residues” conflicts with the limitation of “no other amino acids” of claim 37, upon which claim 57 depends, claim 57 cannot further limit claim 37. In other words, Applicant’s own claim language (“no other amino acids”) excludes the limitation recited in claim 57 from the scope of the claim.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 112
Improper Markush
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.
Claim 43 is rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of “the nucleic acid encodes an enzyme, a receptor, an ion channel, or a protein selected from cystic fibrosis transmembrane conductance regulator (CFTR) and A1AT” is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: The claimed nucleic acids encode structurally and functionally distinct proteins that have distinct uses.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Response to Arguments
Applicant’s amendments necessitated the changes to the grounds of rejection above.
Applicant’s arguments, filed 4th, September, 2025, have been fully considered but are not found persuasive.
Applicant argues the amended Markush grouping is proper (pg. 20-26). Applicant specifically argues “In particular, all remaining DNA sequences in the claims are DNA sequences that encode proteins known in the art. These DNA sequences have known functions. In fact, that these proteins may have different biological activities once the DNA is transcribed into mRNA and then translated into functional protein is not relevant to the issue of compliance with the requirements for a proper Markush group, as the claims at issue do not recite the activity of the proteins and are not limited by specific biological activities of the proteins” (pg. 21)
In response, Applicant has not provided arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use. The Markush grouping of “cystic fibrosis transmembrane conductance regulator (CFTR) and A1AT” is still not proper because as Applicant states “that these proteins may have different biological activities once the DNA is transcribed into mRNA and then translated into functional protein” (pg. 21), means these nucleic acids do not share a single structural similarity or a common use. Specifically, the nucleic encoding these proteins do not share a single structural similarity because they encode structurally distinct proteins and are therefore structurally distinct sequences. Further, the nucleic acids do not share a common use because they are used to encode materially different proteins that have materially different functions and materially different uses such as treating different diseases.
Withdrawn Claim Rejections - 35 USC § 103
The rejection of claims 37, 39, 41-45, and 47-51 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 Heartlein et al. (WO 2015/061467 Al; henceforth “Heartlein”), and Liedberg et al. (US-20120202218-A1; henceforth “Liedberg”) 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 Heartlein et al. (WO 2015/061467 Al; henceforth “Heartlein”), and Liedberg et al. (US-20120202218-A1; henceforth “Liedberg”) 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.
The rejection of claim 46 under 35 U.S.C. 103 as being unpatentable 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 Heartlein et al. (WO 2015/061467 Al; henceforth “Heartlein”), and Liedberg et al. (US-20120202218-A1; henceforth “Liedberg”) 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 withdrawn in view of Applicant’s amendments.
New Claim Rejections - 35 USC § 103
Claims 37, 39, 41-45, and 47-51 are rejected 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”).
Regarding claim 37, Levy discloses nanoparticles for transfection of a cell with a nucleic acid (abstract; pg. 5499-5501), the nanoparticles
comprising:
a cationic peptide comprising lysine and histidine (histidine and lysine; H-K polymer; abstract pg. 5549-5500)
a hydrophilic polymer (polyethylene glycol (PEG)) bonded to a chelator (IDA) coordinated to a metal ion (Zn) and wherein the cationic peptide coordinates to the metal ion (Title; abstract; pg. 5499-5500; Scheme 1).
and
a nucleic acid associated with the cationic peptide through ionic interactions (siRNA; pg. 5549-5500).
However, regarding claim 37, although Levy teaches cationic peptides, Levy does not disclose the peptide is a 4-branched cationic peptide.
Nevertheless, regarding claim 37, Levy cites Leng (pg. 5449-5500). Leng teaches linear and branched cationic peptides for transfection of a cell with a nucleic acid including the 4-branched cationic polypeptide H2K4b (Table 11 pg. 80). Leng teaches branched HK Polymers are more effective than linear HK polymers and more specifically Leng teaches the 4-branched H2K4b HK polymer had the highest transfection (pg. 81 col. 1).
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 Levy, and simply substitute the known prior art element of the 4-branched H2K4b HK polymer of Leng for the linearHK polymer of Levy to obtain the predictable result of a nanoparticle for transfection of a cell with nucleic acid. One or ordinary skill would have been motivated to do so as taught by Leng because the 4-branched H2K4b HK polymer had the highest transfection and was more effective carrier as compared to the linear HK polymer which was used by Levy (pg. 81 col. 1). Regarding the reasonable expectation of success, Levy evidences preparation of nanoparticles for transfection of a cell with HK polymers (abstract; pg. 5499-5501) (histidine and lysine; H-K polymer; abstract pg. 5549-5500) and Leng evidences nanoparticles for transfection of a cell with the 4-branched H2K4b HK polymer (pg. 81 col. 1).
Regarding claim 37, the 4-branched H2K4b HK polymer suggested by Leng above has 3 lysine residues in the core and 4 branches and is therefore sufficient to present an appropriate number of amino groups suitable to accommodate 4 branches off of the lysine core as claimed.
However, regarding claim 37, Levy is silent to including ornithine in the cationic peptide.
Nevertheless, regarding claim 37, Leng suggests substitution of ornithines for lysines could further increase transfection in branched HK peptides (pg. 80 col. 2) and Leng cites Chamarthy (pg. 80 col. 2).
Additionally, regarding claim 37, Chamarthy teaches poly-l-ornithine (PLO) polymers are superior to poly-l-lysine PLL in binding to DNA and in resisting disruption from anions (pg. 484 col. 1 2nd para.). Chamarthy teaches transfection with PLO complexed DNA results in 10-fold higher level of gene expression than with PLL/DNA (pg. 484 col. 1 2nd para.). Chamarthy teaches combing ornithine and histidine repeats in a peptide to assist gene transfer the context of non-viral delivery (pg. 488 discussion; col. 2 1st para.). Chamarthy teaches cationic peptides with PLO were not toxic (whereas peptides with PLL were) and exhibited superior transfection efficiency (pg. 488 discussion; col. 2 para. 1-2).
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 Levy in view of Leng, and simply substitute the Lysine residues of the suggested 4-branched H2K4b HK polymer with poly-l-ornithine (PLO) residues as taught by Leng and Chamarthy 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 by Chamarthy to increase transfection and reduce toxicity (pg. 488 discussion; col. 2 para. 1-2). Furthermore, Chamarthy specifically teaches combing ornithine and histidine repeats in a peptide and it would therefore have been obvious to specifically substitute only the lysines in the lysine and histidine repeats which are in the branches of the suggested H2K4b HK polymer and not the lysine residues of the core. Regarding the reasonable expectation of success, Leng evidences nanoparticles for transfection of a cell with the 4-branched H2K4b HK polymer (pg. 81 col. 1), and Chamarthy evidences combing ornithine and histidine repeats in a peptide to assist gene transfer the context of non-viral delivery (pg. 488 discussion; col. 2 1st para.). Therefore one of ordinary skill in the art would have a reasonable expectation of success in preparing the suggested nanoparticle.
Regarding claim 37, it is noted that the poly-l-ornithine (PLO) residues suggested by Chamarthy above have one S stereocenter and there meets the claimed limitation of containing “all S stereocenters” of instant claims.
Regarding claim 37, it is noted that the substitution of L-ornithine residues for lysine residues in the H2K4b HK polymer suggested above meets the claimed limitation that the cationic peptide comprises histidine (H) and ornithine and no other amino acids.
Regarding claim 37, it is noted that the 4-branched H2K4b HK polymer suggested by Leng above with ornithine residues substituted for lysine residues is 83 residues total which is within the claimed “maximum length of about 150 amino acids and a minimum length of about 50 amino acids.”
However, regarding claim 37, Levy, Leng, and Chamarthy are silent to the nucleic acid as an mRNA and is a functional nucleic acid.
Nevertheless, regarding claim 37, Heartlein teaches nanoparticles for the delivery of a functional nucleic acid (mRNA) (abstract; Background; Examples 3-6; para. [0037, 0376 0463]; Figure 14) to treat the deficiency of CFTR protein in cystic fibrosis (background; Example 5; para. [0037, 0463]).
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 Levy in view of Leng and Chamarthy, and substitute the CFTR mRNA of Heartlein for the siRNA of Levy 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]). Furthermore, it would have been obvious that the mRNA as taught by Heartlein would be associated with the cationic peptide through ionic interactions because the suggested cationic peptide is positively charged and the mRNA is negatively charged. Regarding the reasonable expectation of success, Levy evidences preparation of a nanoparticle comprising a functional nucleic acid (siRNA) and therefore one of ordinary skill would have a reasonable expectation of success in preparing the nanoparticle with the functional nucleic acid mRNA as suggested.
Regarding the wherein clause “the nucleic acid is associated with the cationic peptides through ionic interactions to form a cationic peptides-nucleic acid core” 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 by Levy in view of Leng, Chamarthy and Heartlein which meets all the structural requirements of instant claims (See MPEP 2111.04 regarding wherein clauses).
Regarding the wherein clause “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 (hydrophilic polymer, nucleic acids and cationic peptides) and therefore is met by the nanoparticles as suggested by Levy in view of Leng, Chamarthy and Heartlein which meets all the structural requirements of instant claims (See MPEP 2111.04 regarding wherein clauses).
Regarding claim 39, further to the discussion of claim 37 above, although Levy discloses the nanoparticles were placed in aqueous sodium chloride solution (saline solution), Levy does not disclose that they are provided 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 Levy in view of Leng, Chamarthy and Heartlein, 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 41, further to the discussions of claim 37 above, Leng, Chamarthy and Heartlein are silent to whether the molar ratio of the hydrophilic polymer bonded to a chelator coordinated to a metal ion and the cationic peptide is greater than 28:1.
Nevertheless, regarding claim 41, Levy discloses a 50:1 molar ratio, which is greater than 28.1 and Levy teaches the molar ratio was varied to obtain different degrees of PEG grafting (pg. 5500).
Therefore, regarding claim 41, 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 Levy in view of Leng, Chamarthy and Heartlein and combine the known prior art element of increasing the molar ratio to 50:1 to obtain the predictable result of PEG grafting. One of ordinary skill would have been motivated to do so as taught by Levy to completely inhibit nanoparticle aggregation (pg. 5500). Furthermore, Levy evidences that the molar ratio is a results-effective variable, with an increase in the ratio leading to an increase in stability. Therefore, it would have been predictably obvious to raise the molar ratio to achieve maximum stability. Regarding the reasonable expectation of success, Levy evidences a 50:1 molar ratio (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. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). It is routine procedure to optimize component amounts to arrive at an optimal product that is superior for its intended use, since it has been held where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. See M.P.E.P. §2144.05.
Regarding claim 42, further to the discussion of claim 37 above, Levy teaches the hydrophilic polymer stabilizes the nanoparticles 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, Levy, Leng, Chamarthy and Heartlein are silent to whether there is substantiality no aggregation in 50 mM NaCl for 3 hours.
Nevertheless, regarding claim 42, as stated supra, Levy teaches the nanoparticles resist agglomeration at 100 mM NaCl for 40 minutes (figure 3; pg. 5500).
Therefore, 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 Levy in view of Leng, Chamarthy and Heartlein would have substantiality no aggregation in 50 mM NaCl for 3 hours because the nanoparticles of Levy 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.
Furthermore, regarding claim 42, Levy, Leng, Chamarthy and Heartlein teach the structural requirements of instant claims and therefore the claimed functional properties of substantiality no aggregation in 50 mM NaCl for 3 hours and in Hanks Balanced Salt Solution and SAGM media for at least 7 days at room temperature or at 37° C would naturally follow the preparation of the taught structure.
Regarding claim 43, further to the discussion of claim 37 above, as stated supra, the nucleic acid suggested by Heartlein encodes a protein that is CFTR (abstract; Background; Example 3; para. [0037, 0400, 0429, 0453, 0463, 0474]; Figure 14).
Regarding claim 44, further to the discussion of claim 37 above, Levy, Leng and Chamarthy 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 Levy in view of Leng, Chamarthy and Heartlein, 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]).
Regarding claim 45, further to the discussion of claim 37 above, Levy teaches the nanoparticles have a diameter of approximately 100 nm, which is within the range of about 50 nm to about 250 nm (pg. 5500; Figure 1) and therefore it would be obvious that the nanoparticles suggested by Levy in view of Leng, Chamarthy and Heartlein would have a similar size.
Notably, regarding claim 45, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). It is routine procedure to optimize component amounts to arrive at an optimal product that is superior for its intended use, since it has been held where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. See M.P.E.P. §2144.05.
Regarding claim 47, further to the discussion of claim 37 above, as stated supra, the chelator taught by Levy is iminodiacetic acid (IDA) (abstract; pg. 5499-5501; Figures 2-3).
Regarding claim 48, further to the discussion of claim 37 above, as stated supra, the metal ion taught by Levy is Zn2+ (the Zn in ZnCl2 or Zn(OAc)2 is Zn2+ ;pg. 5499-5501; Scheme 1; Figure 3).
Regarding claim 49, further to the discussion of claims 37 above, Levy teaches the hydrophilic
polymer is mPEG (Title; abstract; pg. 5499-5500; Scheme 1) bonded to iminodiacetic acid (IDA) (abstract; pg. 5499-5501; Figures 2-3) which is coordinated to Zn2+ (the Zn in ZnCl2 or Zn(OAc)2 is Zn2+ ;pg. 5499-5501; Scheme 1; Figure 3).
Regarding claim 51, further to the discussion of claim 37 above, although Levy, Leng and Chamarthy are silent to an extracellular targeting ligand, Heartlein teaches targeting ligands (para. [0409, 0416, 0419]).
Therefore, regarding claim 51, 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 Levy in view of Leng, Chamarthy and Heartlein, and combine the known prior art element of the targeting ligand of Heartlein to obtain the predictable result of a nanoparticle with a targeting ligand. One of ordinary skill would have been motivated to do so as taught by Heartlein to allow the compositions to diffuse from the site of implantation to surrounding cells (para. [0419]). Furthermore, it would have been obvious to choose an extracellular targeting ligand out of the limited genus of extracellular or intracellular targeting ligands. Regarding the reasonable expectation of success, Heartlein evidences targeting ligands (para. [0409, 0416, 0419]).
Hence, the claimed invention as a whole was prima facie obvious.
Response to Arguments
Applicant’s amendment necessitated a new grounds of rejection above with a different combination of art. Therefore, arguments directed to previously set forth rejections are moot in view of the new grounds of rejection above. Nevertheless, for the sake of compact prosecution, arguments considered relevant to the new grounds of rejection are addressed below.
Applicant’s arguments, filed 4th, September, 2025, have been fully considered and are not found persuasive.
Applicant argues “Levy et al. (2010) neither discloses nor suggests the use of any of 2,3 diaminopropionic acid, 2,3-diaminobutyric acid, 2,4-diaminobutyric acid, or ornithine in the cationic polypeptide binding the siRNA or any other nucleic acid molecule that could be bound to the cationic polypeptide. The only nucleic acid disclosed in Levy et al. (2010) was siRNA; DNA was not disclosed. There was no discussion in Levy et al. (2010) regarding stability of PEG-containing nanoparticles that contained DNA, such as plasmid DNA (pidan) or the stability of the pDNA in such nanoparticles.”(pg. 36)
In response, including ornithine in the cationic polypeptide is made obvious by Chamarthy and Leng above.
Regarding DNA, the rejection above addresses the embodiment of mRNA. Neither Levy, nor any other reference cited is currently relied upon for teaching DNA, which is an alternative embodiment that is not currently addressed by the rejection of record because the embodiment of mRNA is rejected above.
Applicant argues “Heartlein et al. '467 neither discloses nor suggests the use of any of 2,3 diaminopropionic acid, 2,3-diaminobutyric acid, 2,4-diaminobutyric acid, or ornithine in any cationic polypeptide binding mRNA for delivery via nanoparticles. In fact, Heartlein et al. '467 does not disclose the use of cationic peptides; in effect, the liposome formulation described in the reference replaces the cationic peptides of Levy et al. (2010)” (pg. 36).
In response, the reference of Heartlein is not relied upon for these teachings and is only relied upon for the specific mRNA. Regarding the argument that “the liposome formulation described in the reference replaces the cationic peptides of Levy” the rejection of record does not allege that liposome formulation replaces or is combined.
Applicant further argues “Heartlein et al. '467 does not disclose the inclusion of DNA in the compositions described in the reference. In Heartlein et al. '467, paragraph [0376] describes the characteristics of the mRNA that can be used, including the protein alternatives that can be encoded by the mRNA, such as, for example, a cytosolic protein. This paragraph has no mention of DNA. The only reference to DNA in Heartlein et al. '467 is its use to be transcribed into the corresponding mRNA. Details of the mRNA structure are described, but these details do not relate to DNA and do not correspond to features present in the DNA that is to be transcribed into mRNA” (pg. 36)
In response, as discussed above, the rejection above addresses the embodiment of mRNA. Neither Levy, nor any other reference cited is currently relied upon for teaching DNA, which is an alternative embodiment that is not currently addressed by the rejection of record because the embodiment of mRNA is rejected above.
Applicant argues with respect to the Liedberg reference (pg. 37-38).
In response, the Liedberg reference is no longer relied upon in the new grounds of rejection above and therefore arguments with respect to this reference are moot.
Applicant argues “The Claims as Amended Are Non-Obvious Over the Combination of References” (pg. 41-44).
In response, these arguments are moot in view of the new grounds of rejection above which relies on a different combination of art.
Further in response to applicant's arguments against the Levy and Heartlein references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In the instant case the rejection of record is based on the new combination of art above which is necessitated by amendment.
Applicant argues “with respect to the Levy Declaration submitted as part of the response to the prior final Office Action, the statement in the Office Action that the instant claims were broad and encompassed a vast number of structurally and functionally distinct sequences needs to be reevaluated in light of the amendments made herein to the claims. These amendments, made to advance prosecution, clarify the scope of the claims; the claims as amended do not include functionally distinct sequences.”
In response, instant claims are drawn to a vast genus of structurally and functionally distinct sequences for the reasons stated above (see rejection under 35 U.S.C. 112a Written Description above) and therefore are still not commensurate in scope with the prior submitted declaration.
New Claim Rejections - 35 USC § 103
Claims 40 and 57 are rejected 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”).
Regarding claim 40, further to the discussion of claim 37 above, Levy, Leng, Chamarthy and Heartlein are silent to whether the cationic peptide to nucleic acid ratio is charge:charge balanced with a ratio between 1:1.2 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 Levy in view of Leng, Chamarthy and Heartlein, 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 1:1.2 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, Levy, Leng, Chamarthy and Heartlein 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 Levy in view of Leng, Chamarthy and Heartlein, 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.
Response to Arguments
Applicant’s amendment necessitated a new grounds of rejection above with a different combination of art. Therefore, arguments directed to previously set forth rejections are moot in view of the new grounds of rejection above. Nevertheless, for the sake of compact prosecution, arguments considered relevant to the new grounds of rejection are addressed below.
Applicant’s arguments, filed 4th, September, 2025, have been fully considered and are not found persuasive.
Applicant argues “Megeed et al. '702 does not disclose or suggest the use of the peptides disclosed in the reference with a hydrophilic polymer bonded to chelators coordinated to metal ions.
Megeed et al. '702 also does not disclose or suggest the use of any of ornithine, 2,3- diaminopropionic acid, 2,3-diaminobutyric acid, or 2,4-diaminobutyric acid in any peptide, polypeptide, or protein in the vectors described in the reference, regardless of the charge balance. Applicant argues Megeed “does not disclose or suggest the use of any of ornithine, 2,3-diaminopropionic acid, 2,3- diaminobutyric acid, or 2,4-diaminobutyric acid” (pg. 47).
In response, Megeed is not relied upon for these teachings and it relied upon to teach combing arginine and to suggest a charge: charge balanced cationic peptide to nucleic acid ratio.
Applicant further argues “Megeed et al. '702 discloses the inclusion of homolysine or homoarginine in the peptides described in the reference. Applicants note that the nanoparticle compositions of the present application do not include homolysine or homoarginine” (pg. 47)
In response, the rejection of record relies on Megeed to teach combing arginine and to suggest a charge: charge balanced cationic peptide to nucleic acid ratio and does not allege that homolysine or homoarginine are also combined.
Applicant further argues “Megeed et al. '702 does not disclose vectors including peptides containing any of ornithine, 2,3-diaminopropionic acid, or 2,4-diaminobutyric acid. Megeed et al. '702 also does not suggest any alternatives for amino acids in the peptides disclosed in the reference, and does not suggest how the amino acid sequences in the peptides would need to be modified in order to retain the activity of the peptides in the vectors if any of ornithine, 2,3-diaminopropionic acid, or 2,4-diaminobutyric acid were included in the peptides” (pg. 48).
In response, Megeed is not relied upon for these teachings and it relied upon to teach combing arginine and to suggest a charge: charge balanced cationic peptide to nucleic acid ratio.
Applicant argues “Because of the differences in three-dimensional structure resulting from the inclusion of any of ornithine, 2,3-diaminopropionic acid, or 2,4-diaminobutyric acid in the peptide, the predictable results required by M.P.E.P. § 2143, Exemplary Rationale (B) are not present” (pg. 49).
In response, while applicant alleges the results are not predictable, Applicant does not provide evidence on the record to support this conclusion.
Applicant is directed to the art of record of Leng et al. (Drug News Perspect. 2007 Mar;20(2):77-86.; henceforth “Leng”). Leng evidences additional functional transfection polypeptides with distinct sequences and different three-dimensional structure (Tables I and II). Therefore, one of ordinary skill would have some predictability that the suggested structure would function to transfect a cell to some amount. Importantly, instant claims do not require a particular amount or efficiency of transfection.
Applicant is reminded that conclusive proof of efficacy is not required to show a reasonable expectation of success. OSI Pharm., LLC v. Apotex Inc., 939 F.3d 1375, 1385, 2019 USPQ2d 379681 (Fed. Cir. 2019) ("To be clear, we do not hold today that efficacy data is always required for a reasonable expectation of success. Nor are we requiring ‘absolute predictability of success.’"); Acorda Therapeutics, Inc. v. Roxane Lab., Inc., 903 F.3d 1310, 1333, 128 USPQ2d 1001, 1018 (Fed. Cir. 2018) ("This court has long rejected a requirement of ‘[c]onclusive proof of efficacy’ for obviousness." (citing to Hoffmann-La Roche Inc. v. Apotex Inc., 748 F.3d 1326, 1331 (Fed. Cir. 2014); PharmaStem Therapeutics, Inc. v. ViaCell, Inc., 491 F.3d 1342, 1364 (Fed. Cir. 2007); Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1364, 1367–68 (Fed. Cir. 2007) (reasoning that "the expectation of success need only be reasonable, not absolute")).
Further, Applicant is directed to MPEP 2143.02 which states that where there is a reason to modify or combine the prior art to achieve the claimed invention, the claims may be rejected as prima facie obvious provided there is also a reasonable expectation of success. The reasonable expectation of success requirement refers to "the likelihood of success" in combining or modifying prior art disclosures to meet the limitations of the claimed invention. See Elekta Ltd. v. ZAP Surgical Sys., Inc., 81 F.4th 1368, 1375, 2023 USPQ2d 1100 (Fed. Cir. 2023) and Intelligent Bio-Sys., Inc. v. Illumina Cambridge Ltd., 821 F.3d 1359, 1367, 119 USPQ2d 1171, 1176 (Fed. Cir. 2016). In other words, while the prior art suggests the reason for modification, it is the preparation of the modification that requires a reasonable expectation of success. Achievement of the desired result, is not necessarily required. In the instant case, the arts of record provide reasonable expectations of success for the preparation of a modification of the nanoparticle for the reasons stated above. The reasonable expectation of success if met by evidence of Levy, Leng, Chamarthy, Heartlein, and Megeed that one of ordinary skill could prepare the structural requirements of the nanoparticle product.
Applicant further argues “If the alternatives disclosed in Megeed et al. '702 would be incorporated into a composition such as disclosed in Levy et al. (2010), there is no basis to conclude that the resulting combination would be functional” (pg. 49).
In response, Megeed is relied upon only to teach combining arginine into the suggested polypeptide and to suggest a charge: charge balanced cationic peptide to nucleic acid ratio. As stated above, 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 and therefore one of ordinary skill would conclude arginine can be included in a cationic peptide to be used for transfection of a cell. While applicant alleges “there is no basis to conclude that the resulting combination would be functional” (pg. 49), Applicant does not provide evidence on the record to support this conclusion.
Claim Rejections - 35 USC § 103
Claim 46 is are rejected 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 Milla et al. (Curr Drug Metab. 2012 Jan;13(1):105-19.; henceforth “Milla”).
Regarding claim 46, further to the discussion of claim 37 above, as stated above, Levy teaches the hydrophilic polymer is mPEG (Title; abstract; pg. 5499-5500; Scheme 1).
However, regarding claim 46, Levy is silent to whether the PEG is linear or branched.
Nevertheless, regarding claim 46, Milla teaches linear mPEG is the most widely used for PEGylation (pg. 6).
Therefore, regarding claim 46, 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 Levy in view of Leng, Chamarthy and Heartlein and combine the known prior art element of the linear mPEG of Milla to obtain the predictable result of an mPEG suitable for PEGylation. One of ordinary skill would have been motivated to do so as taught by Milla because Milla teaches linear mPEG is the most widely used for PEGylation (pg. 6). Regarding the reasonable expectation of success, Milla evidences linear mPEG for PEGylation (pg. 6).
Hence, the claimed invention as whole was prima facie obvious.
Response to Arguments
Applicant’s amendment necessitated a new grounds of rejection above with a different combination of art. Therefore, arguments directed to previously set forth rejections are moot in view of the new grounds of rejection above. Nevertheless, for the sake of compact prosecution, arguments considered relevant to the new grounds of rejection are addressed below.
Applicant’s arguments, filed 4th, September, 2025, have been fully considered and are not found persuasive.
Applicant argues “there is no discussion in Milla et al. (2012) of specific protein or peptide sequences that could be subject to PEGylation, including the specific peptide sequences recited in the
claims of the present application, or how PEGylation could affect the delivery of nucleic acid sequences that need to be expressed in cells that are transfected. In particular, there is no disclosure or suggestion of PEGylation of peptides or polypeptides that include at least one of: 2,3-diaminopropionic acid, 2,3-diaminopropionic acid, 2,4-diaminobutyric acid, and ornithine in Milla et al. (2012)” (pg. 50).
In response, Milla is not relied upon for these teachings in the rejection of record above.
Applicant further argues “the reference includes no discussion of specific protein or peptide sequences that could be subject to PEGylation, including the specific peptide sequences recited in the claims of the present application, or how PEGylation could affect the delivery of nucleic acid sequences that need to be expressed in cells that are transfected”(pg. 51)
In response, the art of Levy teaches mPEG. Milla is relied upon specifically to include linear mPEG. Since PEGylation with mPEG was present in the primary art of Levy, the preponderance of the evidence is that one of ordinary skill would have had a reasonable expectation of success in preparing a functional nanoparticle with the mPEG.
Applicant further argues “In particular, there is no disclosure or suggestion of PEGylation of peptides that include at least one of 2,3-diaminopropionic acid, 2,3-diaminopropionic acid, 2,4-diaminobutyric acid, and ornithine in Milla et al. (2012).” (pg. 51). Applicant further argues “Milla et al. (2012) provides no guidance to one of ordinary skill in the art with respect to the use of 2,3-diaminopropionic acid, 2,4-diaminobutyric acid, or ornithine in the peptides of the claimed invention” (pg. 51).
In response, Milla is relied upon for teaching linear mPEG and is not relied upon for these teachings.
Examiner’s Remark
It is noted that claim 58 was previously indicated as free of the prior art. In the amendment filed 4th, September 2025, new limitations of the branched sequences (ii), (iii) and (iv), that had not previously been considered were added to claim 58. Branched sequences (ii), (iii) and (iv) are considered 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
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
No claim is allowable.
Correspondence
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/BRIANA N EBBINGHAUS/Examiner, Art Unit 1632 /VALARIE E BERTOGLIO/Primary Examiner, Art Unit 1632
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