DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant's election with traverse of Group 1, claims 1-11 in the reply filed on June 30, 2026 is acknowledged. The traversal is on the ground(s) that the special technical feature required by all groups, a nucleic acid sequence encoding a modified LAMP-2B protein from which the intracellular domain, the extracellular domain, or a combination thereof has been removed, makes a contribution over the prior art or Ramratnam and Tang. Applicant traverses that the fusion protein comprising a cargo molecule and an introduced N-terminal (extracellular) domain of LAMP-2B as taught by Ramratnam and Tang is materially different than the instant nucleic acid sequence encoding a LAMP-2B which is defined by the portions of a LAMP-2B protein which are removed and not by the portions of LAMP-2B which are fused to other proteins. Applicant asserts that although Ramratnam and Tang’s SEQ ID NO: 14 shares 100% homology to instantly claimed SEQ ID NO: 2, the Ramratnam and Tang does not disclose which domains of LAMP-2B have been removed and therefore the instant claim makes a contribution over the prior art. Applicant further traverses that because all groups share the same LAMP-2B plasmid, there is no search burden for the separate groups.
This is not found persuasive because the examiner was able to provide art which satisfied the limitations of group I, specifically a nucleic acid sequence encoding a modified LAMP-2B protein from which the extracellular domain of LAMP-2B has been removed (see Leonard et al. as detailed below), thereby demonstrating that the special technical feature lacks novelty. Therefore, a lack of unity exists between the restricted groups.
The requirement is still deemed proper and is therefore made FINAL.
Claims 12-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on June 30, 2026.
Claims 1-11 are examined on the merits.
Priority
The instant application is a 35 U.S.C 371 national stage filing of the International Application No. PCT/KR2022/013574 filed on September 8, 2022. The instant application claims foreign priority under 35 U.S.C 119(a)-(d) to Korean Patent Application(s) KR10-2021-0119735, filed on September 8, 2021 and KR10-2022-011434, filed on September 8 2022. Receipt is acknowledged of a certified copy of the foreign patent application in the original language as required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on March 7, 2024; July 25, 2024; and January 13, 2026 are in compliance with the provisions of 37 CFR 1.97 and are being considered by the examiner.
Applicant is reminded that the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Objection to the Drawings
FIGS. 8, 9, 12, 13, 14, 16, and 25 depict images indicating GFP fluorescence which Applicant references in order to show results of the instant invention. However, the instant figures are provided in black and white which makes determination of Applicant’s results difficult. Appropriate correction is required.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Claim Rejections - 35 USC § 112
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 4-6 and 9-11 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.
Claims 4-6 and 11 encompass a genus of nucleic acid sequences encoding a modified LAMP-2B protein having 70% or more homology to SEQ ID NOs: 2, SEQ ID NO: 3, and/or SEQ ID NO: 4, and which retain the functional ability of expression and delivery of a biomolecule.
Claims 9-10 and 11 encompass a genus of nucleic acid sequences encoding a glycosylated region having 70% or more homology to SEQ ID NOs: 11, SEQ ID NOs: 12, and/or AAC, and which retain the functional ability of triggering glycosylation.
ACTUAL REDUCTION TO PRACTICE
In regard to claims 4-6 and 11 encompassing a genus of nucleic acid sequences encoding a modified LAMP-2B protein having 70% or more homology to SEQ ID NOs: 2, SEQ ID NO: 3, and/or SEQ ID NO: 4, and which retain the functional ability of expression and delivery of a biomolecule, the specification shows a single embodiment for SEQ ID NO: 2 which corresponds to the extracellular (N-terminal) and transmembrane domains of LAMP-2B (full sequence of LAMP-2B in SEQ ID NO: 1), a single embodiment for SEQ ID NO: 3 which corresponds to transmembrane and intracellular (C-terminal) domains LAMP-2B, and a single embodiment of SEQ ID NO: 4 which corresponds to the transmembrane portion of LAMP-2B (See Table 1).
In regard to claims 9-10 and 11 encompassing a genus of nucleic acid sequences encoding a glycosylated region having 70% or more homology to SEQ ID NOs: 11, SEQ ID NOs: 12, and/or AAC, and which retain the functional ability of triggering glycosylation, the specification shows a single embodiment of SEQ ID NO: 11 corresponding to GNSTM, a single embodiment of SEQ ID NO: 12 corresponding to SEL, and a single embodiment of AAC corresponding to a glycine residue (See Table 1).
Therefore, as stated above, it appears that Applicant was only in possession of a limited number of nucleic acids encoding a modified LAMP-2B protein and a limited number of nucleic acids encoding a glycosylation motif which can be used for expression and delivery of a biomolecule.
DISCLOSURE OF STRUCTURE
Regarding modified LAMP-2B proteins, Applicant has provided sequence listings of SEQ ID NOs for three embodiments of modified LAMP-2B proteins: a single embodiment of the extracellular (N-terminal) and transmembrane domains of LAMP-2B designated SEQ ID NO: 2, a single embodiment of the transmembrane and intracellular (C-terminal) domains LAMP-2B designated SEQ ID NO: 3, and a single embodiment of the transmembrane portion of LAMP-2B designated SEQ ID NO: 4 (See Table 1). Regarding glycosylation sequences, Applicant has provided sequence listings of SEQ ID NOs for a single embodiment of a GNSTM sequence designated SEQ ID NO: 11, a single embodiment of an SEL sequence designated SEQ ID NO: 12, and a single embodiment of a glycosylation codon AAC.
The broadest reasonable interpretation of a sequences sharing 70% or greater homology (identity) with the instantly disclosed sequences encompasses nucleic acid sequences having 30% of the nucleotides altered while maintaining the claimed functional ability. Regarding LAMP-2B proteins, SEQ ID NO: 2 has 1203 nucleotides, SEQ ID NO: 3 has 192 nucleotides, and SEQ ID NO: 4 has 162 nucleotides. Thus, the instant claims encompass LAMP-2B sequences comprising up to 360, 57, and 48 nucleotide alterations respectively. Regarding glycosylation sequences, SEQ ID NO: 11 has 15 nucleotides and SEQ ID NO: 12 has 69 nucleotides. Thus, the instant claims encompass glycosylation sequences comprising up to 4, 20, and a single alteration (in the case of the AAV codon).
However, neither the specification nor the art indicate a relationship between the structure of the claimed genus of nucleic acid sequences encoding modified LAMP-2B proteins or glycosylation sequences and the ability to function for expression and delivery of a biomolecule and to trigger glycosylation.
SUFFICIENT RELEVANT IDENTIFYING CHARACTERISTICS
As mentioned above, the complete genus of nucleic acid sequence encoding a modified LAMP-2B protein corresponding to SEQ ID NOs 2, 3, and/or 4 and nucleic acid sequences encoding glycosylation sites corresponding to SEQ ID NOs 11, 12, and/or AAC are not provided.
Accordingly, if the skilled artisan sought to generate the claimed genus of nucleic acid sequences encoding a modified LAMP-2B protein corresponding to SEQ ID NOs 2, 3, and/or 4 and nucleic acid sequences encoding glycosylation sites corresponding to SEQ ID NOs 11, 12, and/or AAC, they would first need to know which nucleic acid sequences encoding amino acids could be chosen to be modified and still be able to predictably produce a modified LAMP-2B protein and trigger glycosylation for use in expression and delivery of a biomolecule. Hence, based on the written description guidelines, the Examiner should conclude that the applicant was not in possession of the claimed genus of codon-optimized nucleic acids beyond the sequences described in the specification.
The breadth of the claims encompass a genus of nucleic acid sequences encoding a modified LAMP-2B protein from which the intracellular and/or extracellular domain have been removed comprising any nucleic acid sequence having 70% homology to SEQ ID NOs: 2-4 and a genus of nucleic acid sequences encoding a glycosylation sites comprising any nucleic acid sequence having 70% homology to SEQ ID NO: 11, 12 and/or AAC. The present specification provides no guidance nor description to any rational in choosing the sequences that were identified; therefore, the skilled artisan would not know what rational approach to take to make modifications with any predictable outcome on generating a modified LAMP-2B protein and glycosylation motif which could function in expression and delivery of a biomolecule. Therefore, it is incumbent on the applicant to provide this nexus between structure and function, in order to be given credit for possession of a larger genus of nucleic acid sequences encoding a modified LAMP-2B protein and glycosylation motif. Otherwise, the Written Description guidelines suggest that the applicant is entitled to only the species specifically recited as having this activity. Moreover, even when several species are disclosed, these are not necessarily representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (“The ’128 and ’485 patents, however, only describe species of structurally similar antibodies that were derived from Joe-9. Although the number of the described species appears high quantitatively, the described species are all of the similar type and do not qualitatively represent other types of antibodies encompassed by the genus.”). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species.
An applicant may show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics. Enzo Biochem, 323 F.3d at 964, 63 USPQ2d at 1613.
STATE OF THE ART & QUANTITY OF EXPERIMENTATION
The method of making the claimed invention is not well established. Although utilization of LAMP-2B fusion proteins in expression and delivery of biomolecules is known in the art, one of ordinary skill would neither expect nor predict the appropriate functioning of the LAMP-2B proteins and triggering of glycosylation according to the claimed genus of nucleic acid sequences as broadly as is claimed.
Even minor changes in amino acid sequences eliminate glycosylation and can affect exosome uptake of a biomolecule as evidenced by Leonard et al. (US 2017/0087087 A1). Leonard discloses use of a mutated motif GASTM, which differs in a single amino acid compared to the known glycosylation motif GNSTM, is not glycosylated which results in reduced uptake of a fused peptide (i.e., RVG) into exosomes (Para. [0170]). Further, a single amino acid alteration of sequence AAC which codes for asparagine, a key player in N-linked glycosylation, could change the resultant amino acid to lysine. Further, Leonard discloses that LAMP-2B comprises other N-linked glycosylation sites and cites Kundra and Kornfeld (1999, Asparagine-linked oligosaccharides protect Lamp-1 and Lamp-2 from intracellular proteolysis. J. of Bio. Chem., 274(43), 31039-31046). Kundra and Kornfeld disclose that LAMP-2 is heavily glycosylated which protect LAMP-2 proteins from degradation in the intracellular environment (Abstract) and that previous studies to prevent glycosylation of proteins disrupts protein folding, resulting in degradation of the proteins (Pg. 31029, bridging para. between cols.). Thus, alterations which might change these glycosylation sites would be expected to result in misfolded LAMP-2B proteins which are degraded by cellular machinery. Further, Leonard et al. discloses that glycosylation is important for sorting of proteins into exosomes and mutations of the glycosylation sites in other exosome proteins, such as EWI-2, decreases the ability of EWI-2 to be sorted into exosomes and suggests that similar alterations of LAMP-2B could similarly reduce the association of LAMP-2B in exosomes (Para. [0173]).
Applicant has claimed a genus of nucleic acid sequences encoding modified LAMP-2B proteins and glycosylation motifs which can be used in expression and delivery of a biomolecule, yet the specification has only managed to identify very specific nucleic acid sequences that can be used as modified LAMP-2B proteins and which trigger glycosylation. Independent of how these specific sequences were derived by Applicant, the prior art discloses that a protein encoding a LAMP-2B protein cannot have any position modified and predictably function in exosomal expression and delivery and a glycosylation motif comprising a single amino acid substitution can completely eliminate glycosylation. Because Applicant has no manner a priori to predict which nucleic acid sequences encoding modified LAMP-2B proteins and glycosylation motifs can be modified and used to encode a functional LAMP-2B protein and glycosylation motif for delivery of a biomolecule, the genus of nucleic acid sequences claimed by Applicant cannot be predictably made or used by the ordinary artisan.
Not knowing, absent further experimentation and screening, which nucleic acid modifications are functional and which are not when, as set forth above, even a single change of an encoded amino acid can unpredictably affect structure and function, leads to one having no predictability or expectation of success for the function of any given nucleic acids sequence encoding a LAMP-2B protein and glycosylation motif. Such random experimentation to identify at a later time what structure or variant or modification is or is not functional and is embraced by Applicant’s claims is undue experimentation. Furthermore, functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. See ABBVIE DEUTSCHLAND GMBH & 2 CO. v. JANSSEN BIOTECH, INC., Appeals from the United States District Court for the District of Massachusetts in Nos. 09-CV-11340-FDS, 10-CV-40003-FDS, and 10-CV-40004-FDS, Judge F. Dennis Saylor, IV. See also Ariad, 598 F.3d at 1351 (“[T]he level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology.”); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1352 (Fed. Cir. 2011) (noting the technical challenges in developing fully human antibodies of a known human protein).
CONCLUSION
Therefore, the examiner concludes that there is insufficient written description of the instantly claimed genus. Specifically, there is limited description of the structure-function relationship between the claimed genus of nucleic acid sequences which encode a modified LAMP-2B protein and their ability to function in expression and delivery of a biomolecule as well as a limited description of the structure-function relationship between the claimed genus of nucleic acids which encode a glycosylation motif and their ability to trigger glycosylation and Examiner further concludes a skilled artisan would find the specification inadequately describes the nucleic acid sequences encoding a LAMP-2B protein and glycosylation motif encompassed by the claimed genus of nucleic acid sequences.
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 4-6 and 9-11 are rejected under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, 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.
Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). The term “homology” in instant claims is used by the claims to mean same nucleic acid sequence, while the accepted term is “identity.” In other words, while amino acid sequences can share a certain percent “homology”, nucleic acid sequences only share percent “identity”. The term is indefinite because the specification does not clearly redefine the term.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1 and 7-10 are rejected under 35 U.S.C. 102(a)(1)/102(a)(2) as being anticipated by Leonard et al. (US 2017/0087087 A1, hereafter “Leonard’).
With regard to claim 1, Leonard discloses an engineered targeting fusion protein which comprises an exosome targeting domain (Para. [0029]) that can be a fragment of LAMP-2B comprising the C-terminus and provides SEQ ID NO: 24 (corresponding to RRKSYAGYQTL) as being the amino acid sequence of the C terminus of LAMP-2B (Para. [0030], [0031], claim 6). Leonard also discloses the nucleic acid sequence which encode the polypeptides (Para. [0062]) which is considered to reasonably read on a nucleic acid encoding a modified protein from which the extracellular domain of LAMP-2B has been removed. Leonard discloses that the fusion protein may optionally include a portion of the transmembrane domain (Para. [0031]). Leonard discloses that the fusion proteins can be used in an extracellular vesicle for delivery of an agent (Para. [0036]) and that the nucleic acid encoding the fusion protein may be introduced into a host via a plasmid (Para. [0073], [0075], [0076], [0084], [0150]).
With regard to claim 7, Leonard discloses that the nucleic acid sequence encoding a fusion protein comprising a modified LAMP-2B protein comprises an engineered glycosylation motif (Para. [0017], [0151], Example 5 Para. [0166]).
With regard to claim 8, Leonard discloses that the fusion protein the fusion protein has a luminal N-terminus and a cytosolic C-terminus and the fusion protein comprises from N-terminus to C-terminus: the ligand, the glycosylation site, and the exosome-targeting domain (i.e., LAMP-2B) (Para. [0025]; Example 5 Para. [0166], claim 5). This is considered to reasonably read on the glycosylation site being located extracellularly based on the modified protein.
With regard to claim 9 and 10, Leonard discloses that the glycosylation motif can be a GNSTM sequence (SEQ ID NO: 38) (Para. [0027], [0151], [0166], claim 7), which is considered to reasonably read on SEQ ID NO: 11 (see also search report dated 08/28/2026, SEQ ID NO: 11, .rapbm file, result 1).
PNG
media_image1.png
88
380
media_image1.png
Greyscale
Claims 1-4 are rejected under 35 U.S.C. 102(a)(1)/102(a)(2) as being anticipated by Liu et al. US 2018/0104187 A1, found in IDS dated 07/25/2026, hereafter “Liu”).
With regard to claim 1, Liu discloses a plasmid comprising a nucleic acid sequence encoding a modified fusion protein which comprises the transmembrane and cytoplasmic (intracellular) domains of lysosome-associated membrane glycoprotein (LAMP-2B) and where the extracellular domain is replaced with a mutant SIRPα domain (Para. [0027], Fig. 25), which is considered to reasonably read on a nucleic acid sequence from which the extracellular domain of LAMP-2B has been removed. Liu discloses that the nucleic acid can be used in an extracellular vesicle for delivery of a molecule (Para. [0043], Example 2).
With regard to claims 2 and 3, as detailed above, Liu teaches a plasmid comprising a nucleic acid sequence encoding a modified fusion protein which comprises the transmembrane and cytoplasmic (intracellular) domains LAMP-2B, which is considered to reasonably read on a nucleic acid sequence from which the extracellular domain of LAMP-2B has been removed, and use of the fusion protein for delivery of a molecule. In other embodiments, Liu teaches that the fusion protein comprising LAMP-2B can comprise the transmembrane domain or a portion thereof (Para. [0011], [0067], [0068], [0075], see also claims 17, 20, and 22). This is considered to reasonably read on a nucleic acid sequence encoding a protein from which the intracellular domain (claim 2) and the extracellular domain (claim 3) have been removed.
With regard to claim 4, Liu discloses SEQ ID NO: 2 which comprises a nucleic acid sequence having 100% homology to instantly claimed SEQ ID NO: 3 over the region spanning the signal peptide, transmembrane domain, and intracellular C terminus. (signal peptide in italics, transmembrane domain in bold, intracellular C terminus underlined).
Liu’s SEQ ID NO: 2 (mutant SIRPα extracellular domain highlighted)
ACC ATG GTG TGC TTC CGC CTC TTC CCG GTT CCG GGC TCA GGG CTC GTT CTG
GTC TGC CTA GTC CTG GGA GCT GTG CGG TCT TAT GCA GGA GGT GGC AGT GGA
GGT GGC AGT GAG GAG GAG CTG CAG ATT ATT CAG CCT GAC AAG TCC GTG TTG
GTT GCA GCT GGA GAG ACA GCC ACT CTG CGC TGC ACT ATT ACC TCT CTG TTT
CCT GTG GGG CCC ATC CAG TGG TTC AGA GGA GCT GGA CCA GGC CGG GTT TTA
ATC TAC AAT CAA CGC CAA GGC CCT TTC CCC CGG GTA ACA ACT GTT TCA GAC
ACT ACA AAG AGAAACAACATG GAC TTT TCC ATC CGC ATC GGT AAC ATC ACC
CCA GCA GAT GCC GGC ACC TAC TAC TGT ATT AAG TTC CGG AAA GGG AGC CCC
GAT GAC GTG GAG TTT AAG TCT GGA GCA GGC ACT GAG CTG TCT GTG CGC GCC
AAA CCC TCT GCC CCC GGA GGT AGT GGC GGA GGT AGT GGC CTA ATC CCA ATT
ATA GTT GGT GCT GGT CTT TCA GGC TTG ATT ATC GTT ATA GTG ATT GCT TAC
GTA ATT GGC AGA AGA AAA AGT TAT GCT GGA TAT CAG ACT CTG TAA
Instant SEQ ID NO: 3
atggtgtgct tccgcctctt cccggttccg ggctcagggc tcgttctggt ctgcctagtc ctgggagctg tgcggtctta tgcactaatc ccaattatag ttggtgctgg tctttcaggc ttgattatcg ttatagtgat tgcttacgta attggcagaa gaaaaagtta tgctggatat cagactctgt aa
PNG
media_image2.png
468
810
media_image2.png
Greyscale
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 5-6 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (US 2018/0104187 A1, found in IDS dated 07/25/2026, hereafter “Liu”) as evidenced by Ramratnam and Tang (WO 2019,169216 A1).
With regard to claim 5 and 6, as detailed above, Liu teaches a plasmid comprising a nucleic acid sequence encoding a modified fusion protein which comprises the transmembrane and cytoplasmic (intracellular) domains LAMP-2B, which is considered to reasonably read on a nucleic acid sequence from which the extracellular domain of LAMP-2B has been removed, and use of the fusion protein for delivery of a molecule. In other embodiments, Liu teaches that the fusion protein comprising LAMP-2B can comprise the transmembrane domain or a portion thereof (Para. [0011], [0067], [0068], [0075], see also claims 17, 20, and 22).
Although Liu clearly contemplates a nucleic acid sequence which encodes only the transmembrane domain of a LAMP-2B protein, Liu is silent as to the specific nucleotide sequence corresponding to the transmembrane domain.
ACC ATG GTG TGC TTC CGC CTC TTC CCG GTT CCG GGC TCA GGG CTC GTT CTG
GTC TGC CTA GTC CTG GGA GCT GTG CGG TCT TAT GCA GGA GGT GGC AGT GGA
GGT GGC AGT GAG GAG GAG CTG CAG ATT ATT CAG CCT GAC AAG TCC GTG TTG
GTT GCA GCT GGA GAG ACA GCC ACT CTG CGC TGC ACT ATT ACC TCT CTG TTT
CCT GTG GGG CCC ATC CAG TGG TTC AGA GGA GCT GGA CCA GGC CGG GTT TTA
ATC TAC AAT CAA CGC CAA GGC CCT TTC CCC CGG GTA ACA ACT GTT TCA GAC
ACT ACA AAG AGAAACAACATG GAC TTT TCC ATC CGC ATC GGT AAC ATC ACC
CCA GCA GAT GCC GGC ACC TAC TAC TGT ATT AAG TTC CGG AAA GGG AGC CCC
GAT GAC GTG GAG TTT AAG TCT GGA GCA GGC ACT GAG CTG TCT GTG CGC GCC
AAA CCC TCT GCC CCC GGA GGT AGT GGC GGA GGT AGT GGC CTA ATC CCA ATT
ATA GTT GGT GCT GGT CTT TCA GGC TTG ATT ATC GTT ATA GTG ATT GCT TAC
GTA ATT GGC AGA AGA AAA AGT TAT GCT GGA TAT CAG ACT CTG TAA
However, Liu teaches SEQ ID NO:2 which comprises the transmembrane domain and intracellular domain of LAMP-2B and which comprises 100% homology to instantly claimed SEQ ID NO:3 across those domains (as detailed supra). LAMP-2B is a well-known protein for which the various domains have been mapped as evidenced by Ramratnam and Tang which evidences the portion of LAMP-2B corresponding to the transmembrane domain (Pg. 12, middle para.). As Liu teaches SEQ ID NO: 2 comprising the transmembrane domain and intracellular region, a skilled artisan would have been able to easily derive the nucleic acid sequence of LAMP-2B which corresponds to the transmembrane domain and which would share 100% homology with instantly disclosed SEQ ID NO: 4. Therefore, A skilled artisan would have been motivated to engineer a fusion protein comprising only the LAMP-2B transmembrane domain corresponding to instant SEQ ID NO: 4 and would have had a reasonable expectation of success because Liu teaches that the fusion protein comprising LAMP-2B can comprise at minimum only the LAMP-2B transmembrane domain or a portion thereof and maintain functional ability.
PNG
media_image3.png
468
920
media_image3.png
Greyscale
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Leonard et al. (US 2017/0087087 A1, hereafter “Leonard’).
With regard to claim 11, as detailed supra, Leonard teaches a plasmid comprising an engineered targeting fusion protein comprising the C-terminal fragment of LAMP-2B and provides SEQ ID NO: 24 (corresponding to RRKSYAGYQTL) as the amino acid sequence of the C-terminus of LAMP-2B (Para. [0030], [0031], claim 6) as well as the nucleic acids encoding the proteins. Leonard also teaches that the fusion protein comprising a modified LAMP-2B protein can comprise an engineered glycosylation motif (Para. [0017], [0151], Example 5 Para. [0166]) which is a GNSTM sequence (SEQ ID NO: 38) (Para. [0027], [0151], [0166], claim 7), which is considered to reasonably read on SEQ ID NO: 11 (see also search report dated 08/28/2026, SEQ ID NO: 11, .rapbm file, result 1). Leonard teaches that inclusion of a glycosylation motif serves to protect the peptide fused to LAMP-2B from degradation and enhances delivery (Para. [0144]). Further, Leonard discloses that the fusion protein may also include a portion of the transmembrane domain (Para. [0031]) and provides SEQ ID NO: 21 as the sequence of full length LAMP-2B protein (Para. [0030], [0053]). SEQ ID NO: 21 as taught by Leonard shares 100% homology to instantly claimed SEQ ID NO: 4 comprising the transmembrane domain of LAMP-2B (See search results dated 08/28/2026, SEQ ID NO: 4 .rapbm file, result 16, duplicate 48). This is considered to reasonably read on a nucleic acid sequence having 70% or more homology with a nucleic acid sequence of SEQ ID NO: 4.
PNG
media_image4.png
344
784
media_image4.png
Greyscale
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention, to use a fusion protein which includes the transmembrane domain of LAMP-2B (i.e., a nucleic acid sequence having 70% or more homology with a nucleic acid sequence of SEQ ID NO: 4) as well as a nucleic acid sequence comprising a GNSTM glycosylation motif having SEQ ID NO: 11 with a reasonable expectation of success. A skilled artisan would have been motivated to use a fusion protein including a nucleic acid having SEQ ID NO: 4 as Leonard teaches that the fusion protein can comprise the transmembrane domain as well as the C terminus and provides SEQ ID NO: 21 for reference of LAMP-2B. Further, Leonard teaches that inclusion of a GNSTM glycosylation motif (i.e., SEQ ID NO: 11) provides protection for degradation and improved delivery for peptide fused the LAMP-2B proteins (Para. [0144]). One having ordinary skill in the art would have had a reasonable expectation of success as Leonard clearly contemplates inclusion of the transmembrane domain of LAMP-2B in the fusion protein and teaches that glycosylation is beneficial for delivery of peptides.
Note that the successful cloning and sequencing of the cDNA encoding a known protein is obvious, and thus unpatentable, if (1) there was some suggestion or motivation in the prior art to clone the cDNA, and (2) there was a “reasonable expectation of success,” based on "detailed enabling methodology" in the prior art. Ex parte Kubin, 83 U.S.P.Q.2d (BNA) 1410 (B.P.A.I. 2007), aff'd, 561 F.3d 1351 (Fed. Cir. 2009).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERIN V PAULUS whose telephone number is (571)272-6301. The examiner can normally be reached Mon-Fri 8 AM-5 PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Doug Schultz can be reached at 571-272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ERIN V PAULUS/Examiner, Art Unit 1631
/ARTHUR S LEONARD/Examiner, Art Unit 1631
Prosecution Insights