DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicant’s amendment filed on February 12, 2026 is acknowledged.
Claims 2-5, 16-27, 29-36, 38-47, and 51-54 have been canceled.
Claims 55-57 have been added.
Claims 1, 6-15, 28, 37, 48-50, and 55-57 are pending and currently under consideration.
3. In view of applicant’s statement pursuant to 35 U.S.C. 102(b)(2)(c), the previous rejection under 35 U.S.C. 102(a)(2) as being anticipated by Spangler et al. (US 2022/0372098) has been withdrawn.
Applicant states that no later than the effective filing date of claims 48 and 49, the subject matter disclosed in Spangler et al. and the instant application were either owned by the same person or subject to an obligation of assignments to the same person.
4. In view of applicant’s amendment, following rejections are set forth.
5. The specification is objected to as failing to provide proper antecedent basis for the claimed subject matter. See 37 CFR 1.75(d)(1) and MPEP § 608.01(o). Correction of the following is required:
The previous Office Action states:
“Applicant is requested to identify the written support for claim 6, particularly the claimed limitation of “sialic acid 9-phosphate synthase (SAS) or other bottlenecks in a sialic acid biosynthetic pathway”. Applicant is requested to identify the written support for ManNAc analogs appended with the chemical functional groups recited in claims 10-15”.
Applicant asserts that claim 6 has been canceled. But claim 6 is not canceled.
In addition, applicant asserts that the support for claims 10-15 are found in [0051], [0143], [0158], [0191], and FIGS 2 and 6.
However, the instant specification does not have support for unsaturated alkyl or a saturated alkyl as recited in claims 10-15.
As such the objection to the specification has been maintained for the reasons of record.
6. The instant application appears to be in sequence compliance for patent applications containing nucleotide sequence and/or amino acid sequence disclosures, except for the following:
It does not appear that all of the sequences disclosed in the specification as filed are provided with the appropriate SEQ ID NOS. in compliance with the Sequence rules as set forth in 37 CFR 1.821(d).
For example, the polynucleotide sequences disclosed in Tables 2-5 in pages 46-55 in the instant specification does not appear to have SEQ ID NOs.
Applicant is reminded of the Sequence Rules which require a submission for all sequences of 10 or more nucleotides or 4 or more amino acids (see 37 CFR 1.1821-1.1825) and is also requested to carefully review the submitted specification for any and all sequences which require compliance with the rules.
7. 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.
8. Claim 6 is 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 6 recites the limitation "wherein one or more enzymes that modulate sialylation…." in line 1. There is insufficient antecedent basis for this limitation in the claim. Claim 6 is depended upon claim 1 which recites one or more enzyme selected from a group including sialyltransferases not one or more enzyme that modulate sialylation.
9. 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.
10. Claim 49, and newly added claims 55, and 56 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention for the reasons of record.
The amended claim 49 now recites a modified immunoglobulin comprises SEQ ID NOs: 1 and 2. The specification discloses that SEQ ID NOs:1 and 2 are the VH and VL of antibody clone 602, respectively. However, claim 49 does not recite antigen specificity. Thus, while one of skill in the art could make the immunoglobulin VH and VL having the specific amino acid sequences as recited, as discussed in the previous Office Action (mailed on August 12, 2025), the skill in the art would not be able to use the immunoglobulin without knowing the antigen specificity.
Further, newly added claim 55 encompasses an amino acid sequence at least 90% identical to one or more of SEQ ID NO:1-12 or combination thereof. Newly added claim 56 encompass the expression vector encodes a peptide having at least 90% identity to one or more of SEQ ID NOs: 1-12 or combination thereof.
Applicant’s arguments have been fully considered but have not been found persuasive.
Applicant argues that claim 49 has been amended to recite the amino acid sequences for both VH and VL. Thus, applicant asserts that the rejection should be withdrawn.
This is not found persuasive for following reasons:
Contrary to applicant’s assertion, note that claim 49 does not recite antigen specificity. Thus, while one of skill in the art could make the immunoglobulin VH and VL having the specific amino acid sequences as recited, as discussed in the previous Office Action (mailed on August 12, 2025), the skill in the art would not be able to use the immunoglobulin without knowing the antigen specificity.
Newly added claims 55 and 56 recites an amino acid sequence or expression vector encodes a peptide that is at least 90% identical to SEQ ID NO:1-12. In addition, the claims recite one or more of SEQ ID NOs:1-12.
The instant specification does not provide sufficient guidance as to how the skilled artisan would use the various amino acids sequences recited in the instant claims or which amino acids within SEQ ID NOs: 1-12 can be changed. A person skill in the art would not be able to predict which additional CDRs are to be paired together to form a functional antibody with no antigen specificity.
As stated previously, it is well established in the art that the formation of an intact antigen-binding site generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs which provide the majority of the contact residues for the binding of the antibody to its target epitope. The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites. Even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function.
For example, Chiu et al. (Antibodies 2019, 8,55; 1-80) teach that of all of the six CDRs, the VH CDR3 most often has changes in conformation with unbound and bound structures are compared. In addition, differences in the orientation of VL with respect to VH are often seen and the induced-fit mode of binding introduces plasticity into the antigen-binding site, expanding antibody diversity beyond that resulting from amino acid residue changes (e.g. see page 5). Further, Chiu et al. teach that studies conducted with multiple institutes in predicting CDRs structure do not appear to yield reliable results (e.g. see 1.2.6. Antibody Modeling in page 6).
Sela-Culang et al. (Frontiers in Immunology, 2013, Vol. 4, Article 302, pages 1-13) shows that each CDR has its own unique amino acid composition different from the composition of other CDRs (e.g. see right col. in page 5). In addition, Sela-Culang et al. teach that each CDR has a unique set of contact preferences, therefore, favoring certain amino acids over others (see lines spanning pages 5-6). Sela-Culang et al. also teach that many attempts to isolate and design individual antigen-binding CDR or CDR derived peptides have failed and it is possible that a CDR on its own may not fold to the same conformation as in the context of the entire Fab crucial for antigen binding (e.g. see first full paragraph in the left col. in page 7).
Therefore, it is unlikely that the one or more amino acid sequences of SEQ ID NOs: 1-12 disclosed as the amino acid sequences for VH or VL, which contain not all CDRs (e.g. only three CDRs from either heavy chain or light chain and without reciting the antigen specificity) would enable one of ordinary skill in the art to make and use such sequences that are at least 90% identical to SEQ ID NOs: 1-12 and without VH and VL pair.
The specification provides insufficient direction or guidance regarding how to use the single chain immunoglobulin without the pairing VH or VL and without the antigen the immunoglobulin would bind. Undue experimentation would be required to produce the invention commensurate with the scope of the claim. Moreover, there is insufficient guidance and direction in the specification to show which amino acids within the SEQ ID NOs: 1-12 can be mutated. For example, the specification discloses SEQ ID NO:5 is the amino acid sequences for F5111 and M4-M6 heavy chain and SEQ ID NO:7 is the amino acid sequence of antibody 7M1 heavy chain (e.g. see page 61 of the specification as-filed). There is no disclosure to combine SEQ ID NOs: 5 and 7. A skill in the art would not have be enabled to combine SEQ ID NOs: 1-12 in random orders as encompassed by the instant claims.
In view of the quantity of experimentation necessary, the limited working example, the unpredictability of the art, the lack of sufficient guidance in the specification, and the breadth of the claims, it would take undue trials and errors to make and use the claimed amino acid sequence or a peptide having at least 90% identity to one or more amino acid sequence comprising SEQ ID NOs: 1-12 or combination thereof.
11. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
12. 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.
13. Claims 1, 28, 37, 48, and 50 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Co et al. (US 2003/0054497, reference on IDS) for the reasons of record.
The previous Office Action mailed on August 12, 2025 states:
“Co et al. teach an engineered protein comprising a modified amino acid sequence that is an N-glycan consensus sequence Asn-X-Ser and a method of producing the engineered protein by introducing the consensus sequence into the polynucleotide sequence of the parent protein followed by expressing the protein (e.g. see claims 1-6). Co et al. further teach a modifed cell containing a polynucleotide encodes a mutant antibody that is glycosylated (e.g. see claims 18-29). Co et al. teach working examples of producing the engineered protein that is a humanized anti-CD33 antibody by modifying the genes encoding the antibody, insert them into an expression vector and transfected the vector into Sp2/0 host cells (e.g. see [0063]-[0064]). Co et al. further teach engineered antibody contains Asn-Ser-Ser site that is a recognition sequence for N-linked glycosylation and shows that the antibody is N-glycosylated (e.g. see [0066]-[0068]). Given that the engineered antibody produced is N-glycosylated, the host cell Sp2/0 host cells would contain enzymes N-acetylglucosaminyltransferase in order to achieve the N-glycosylation. Co et al. further teach that the anti-CD33 antibody can be administered to treat cancer (e.g. see [0051])”
Applicant’s arguments have been fully considered but have not been found persuasive.
Applicant argues Co et al. teach modification in the variable domain that change the pattern of glycosylation in the V region while the instant application discloses genetic modification in the host production cells that builds the expression of key proteins involved in glycoprotein production that are lacking in wild type CHO cells or knocks out in [0008]. Applicant further asserts that Co et al. does not teach engineering host cells and sialylation of protein. Thus, applicant asserts that the rejection should be withdrawn.
This is not found persuasive for following reasons:
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., modification to express key protein in CHO cells and sialylation of protein) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Here, the instant amended claim 1 recites a method of producing a modified host cells for producing engineered protein or peptide comprising:
transfecting host cells with an expression vector encoding the protein or peptide comprising one or more genetic mutations that encodes for one or more primary amino acid sequences modified to produce new sites of glycosylation, and
the host cell comprises one or more enzymes selected from N-acetylglucosaminyltransferase, sialyltransferases, Neu5Ac tranporters, thereby producing a modified protein peptide.
The independent claim 1 and the dependent claims in this rejection do not exclude that the genetic mutation from the variable domains, but only require that “one or more genetic mutations encode for one or more primary amino acid sequences modified to produce new sites of glycosylation”. Further, the claims also require the host cell that express one or more enzymes including N-acetylglucosaminyltransferase.
Co et al. teach engineering anti-CD33 antibody from the parent (primary amino acid sequences) to comprise new modified amino acid sequences allowing for glycosylation (e.g. see claims 1-6). Co et al. further teach a modified cell host cell Sp2/0 containing a polynucleotide encodes the mutant anti-CD33 antibody that produces the antibody that is N-glycosylated. Given that the engineered antibody produced is N-glycosylated, the host cell Sp2/0 host cells would contain enzymes N-acetylglucosaminyltransferase in order to achieve the N-glycosylation. Co et al. further teach that the anti-CD33 antibody can be administered to treat cancer (e.g. see [0051]).
Therefore, the reference teachings anticipate the instant claims.
As such, applicant’s arguments have not been found persuasive.
14. Claims 1, 6-15, 28, 37, 48, and newly added claim 57 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gerngross (US 2006/0177898).
The previous Office Action mailed on August 12, 2025 states:
“Gerngross teaches a method of producing a genetically engineered host cell transfected with an expression vector encoding a protein comprising an Fc region comprising one or more mutations wherein the Fc comprises complex N-glycoside-linked sugar chains (e.g. see [0020], [0048], and claims 100-115). Gerngross further teach that the engineered host cell comprises enzymes N-acetylglucosaminyltransferase (e.g. see [0049] and Example 2), sialyltransferase (e.g. see Example 4), and Golgi specific transporters such as CMP-N-acetylneuramic acid (e.g. see [0067]). Gerngross teaches providing sugar nucleotide precursors to the Golgi apparatus including UDP-GlcNAc transporters, GDP-fucose transporter, UDP-galactose transporter or CMP-sialic acid transporter, which are required for the transfected enzymes. CMP-sialic transporter that facilitates the sialyltransferase is considered a hexosamine analogs without evidence to the contrary. Gerngross teach that the engineered host cells are yeast cells and filamentous fungi that does not contain UDP-N-acetylglucosamine (e.g. see [0008]). Gerngross taches IgG antibody produced by the methods, such IgG would have the N-glycan consensus sequence in the Fc region wherein the N-glycan is attached (e.g. see [0004] and claim 116)”.
In addition, Gerngross teaches engineered host cells comprises N-acetylglucosamineinyltransferase, and sialytransferase (e.g. see Examples 2 and 4).
Applicant’s argument shave been fully considered but have not been found persuasive.
Applicant argues that Gerngross does not teach all enzymes taught by applicant including sialic acid 9-phosphate synthase (SAS), enzymes that modulate sialic acid metabolic flux, high flux ManNAc analogs. Therefore, applicant asserts that the rejection should be withdrawn.
This is not found persuasive for following reasons:
Contrary to applicant’s assertion that Gerngross does not teach all enzymes including SAS, note that the only claim recites SAS is claim 6 that recites “wherein one or more enzymes that modulate sialylation comprises sialic acid 9-phosphate synthase (SAS) or other bottlenecks in a sialic acid biosynthetic pathway”.
While Gerngross does not teach SAS, Gerngross provides diagram of human N-glycosylation pathway showing enzymes upstream of sialyltransferase such as β1,4-galactosetransferase that produces precursors for sialyltransferase (e.g. see FIG. 1B). Given that these enzymes upstream of sialyltransferase provide substrates for sialic acid synthesis, they would be considered bottlenecks in the sialic acid biosynthetic pathways without evidence to the contrary.
Regarding high flux ManNAc analogs recited in instant claim 11, Gerngross teaches genetically modified host cell that expresses exogenous enzyme that trims N-glycans such as Man8GlcNAc2 to yield Man5GlcNAc2 in endoplasmic reticulum or Golgi, and Man5GlcNAc2 is a substrate for further glycosylation reactions that produce a finished N-glycan that is similar to that formed in mammals (e.g. see [0036]). Given that Gerngross teaches converting Man8GlcNAc2 to Man5GlcNAc2, the Man5GlcNAc2 would be a high flux of ManNAc analog.
As such, applicant’s arguments have not been found persuasive.
15. Claims 1, 6, 12-14, 28, 37, 48, and newly added claim 57 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Braddock et al. (The FASEB Journal 2019, April 1, supplement 801.1, pages 1-4) for the reasons of record.
Braddock et al. teach a recombinant fusion protein consisting of the extracellular domain of Ectonucleotide pyrophosphatase Phospodiesterase-1 (ENPP-1) fused with the Fc domain of IgG1, wherein the ENPP-1 consists of additional N-glycan consensus sequence (e.g. see page 1). Braddock et al. further teach that the fusion protein is produced in CHO cell line stably transfected with human alpha 2, 6,-sialytransferase and incubated the cell with
N-acetylmannosamine or ManNAc high flux precursor of sialic acid (e.g. see paragraph spanning pages 1-2). It was known in the art that CHO cell comprises N-acetylglucosaminyltransferase.
Applicant’s arguments have been fully considered but have not been found persuasive.
Applicant argues that Braddock et al. is silent with respect to enzymes disclosed by applicant and also do not teach a host cell specifically engineered to produce the proteins disclosed by applicant. As such, applicant asserts that the rejection should be withdrawn.
This is not found persuasive for following reasons:
Contrary to applicant’s assertion, Braddock et al. teaches CHO cells modified for producing an engineered ENPP-1-Fc of IgG1 fusion protein that contains genetic mutations for additional new site for N-glycosylation (e.g. see pages 1-2). Braddock et al. further teaches a method of recombinantly producing the fusion protein by culturing the CHO cells modified genetically to produce the fusion protein and stably transfected with human alpha-2,6-sialytransferase. As such, the teachings of Braddock et al. anticipate the instant invention.
16. No claim is allowed.
17. 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.
18. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHUN DAHLE whose telephone number is (571)272-8142. The examiner can normally be reached Mon-Fri 6:30am-4:00pm.
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, Misook Yu can be reached at 571-272-0839. 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.
/CHUN W DAHLE/Primary Examiner, Art Unit 1641
Prosecution Insights