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
1. Applicant’s election of Group 1, claims 2-8, 10-12, 14, 15 and 16, and the species 1) a deletion at amino acid position 329 (A329) according to EU index numbering as in Kabat, 2) a sequence of amino acid positions 221-447 according to EU index in SEQ ID NO:2, 3) an antibody comprising a heavy chain set forth in SEQ ID NO:2 and a light chain set forth in SEQ ID NO:9 in the reply filed on June 19, 2026 is acknowledged. Because Applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
2. Claims 2-17 are pending.
3. Claims 9, 13 and 17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. An antibody comprising a heavy chain set forth in SEQ ID NO:2 and a light chain set forth in SEQ ID NO:9 is free of prior art. The antibodies of claim 7 were rejoined for consideration.
4. Claims 2-8, 10-12, 14, 15 and 16 are currently under consideration.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). See FIG. 1. Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specification
5. The use of the terms Herceptin and Genentech, which are trade names or marks used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore, the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™,SM, or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Rejections - 35 USC § 112
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.
6. Claims 3 and 6 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.
Regarding claims 3 and 6, the term "preferably" renders the claim indefinite because it is unclear whether the limitation(s) following the term are part of the claimed invention. See MPEP § 2173.05(d).
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.
7. Claim(s) 2-6, 8, 10-12, 14, 15 and 16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 2014/0051834 A1 (Hoffman et al. Feb. 20, 2014), “Hoffman”.
Hoffman teaches an Fc-region fusion polypeptide or Fc-region conjugate comprising a mutation of the amino acid residue at position 329 according to the EU index of Kabat, wherein the mutation is a deletion. See abstract and ¶¶ 0021, 0184, 0185, 0224 and 0284-0287.
Hoffman teaches the Fc region is a human Fc-region of the human IgG1 isotype or of the human IgG4 isotype. See ¶¶ 0025, 00027 and 0044.
Hoffman teaches wild-type human Fc-region of the IgG1 isotype (SEQ ID NO: 42). See ¶¶ 0225. SEQ ID NO: 42 of Hoffman is 98% identical to amino acid positions 221-447 according to EU index in SEQ ID NO: 2. See Appendix.
Hoffman teaches an Fc-region fusion polypeptide or conjugate comprising an Fc-region of an antibody, in one embodiment of a human antibody. See ¶¶ 0280, 0281, 0327 and Example 1.
Hoffman teaches pharmaceutical formulations comprising an Fc-region fusion polypeptide or Fc-region polypeptide conjugate, as described herein, and one or more pharmaceutically acceptable carriers. See ¶¶ 0038, 0252, 0253 and 0412-417.
Hoffman teaches isolated nucleic acid expression vectors for expression of the Fc polypeptides in host cells and methods of using the recombinant host cells to prepare the Fc polypeptides. See ¶¶ 0399-0411.
Regarding claim 14, the kit does not require any components other than the Fc mutant of claim 2. Additionally, Hoffman teaches an article of manufacture containing materials useful for the treatment, and/or prevention of the disorders described above is provided. The article of manufacture comprises a container and a label or package insert on or associated with the container. Suitable containers include, for example, bottles, vials, syringes, IV solution bags, etc. The containers may be formed from a variety of materials such as glass or plastic. See ¶¶ 0447. Thus, the teachings of Hoffman meet the limitations of the claim.
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.
8. Claim(s) 2-8, 10-12, 14, 15 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over US 2015/0104444 A1 (Robblee et al. Apr. 16, 2015), “Robblee” in view of US 2014/0051834 (Hoffman et al. Feb. 20, 2014), “Hoffman”.
Robblee teaches methods for evaluating, identifying, and/or producing (e.g., manufacturing) trastuzumab. See abstract and ¶¶ 0006-0008.
Robblee teaches that the proteins of the invention include Fc fusion proteins containing the Fc region of IgG1. See ¶¶ 0023.
Robblee teaches that the glycoprotein trastuzumab comprises SEQ ID NO: 1 and SEQ ID NO: 2. SEQ ID NO: 1 of Roblee is 99% identical to SEQ ID NO: 27, the only difference being the deletion of proline 329. See Appendix. SEQ ID NO: 2 of Roblee is identical to SEQ ID NO: 34. See Appendix.
Robblee teaches making trastuzumab as a pharmaceutical composition. See ¶¶ 0016, 0020 and 0041.
Robblee teaches nucleic acids that can be used to produce trastuzumab. See ¶¶ 0036.
Robblee teaches combining trastuzumab with other elements to make a kit. See ¶¶ 0042.
Robblee teaches as set forth above but does not teach that the Fc region of trastuzumab contains a deletion of the amino acid at position 329 of the Fc region.
Hoffman teaches as set forth above.
Hoffman additionally teaches that changing the proline residue at position 329 of an antibody heavy chain Fc-region to glycine results in the inhibition of the Fcg RIIIA and FcgRIIA receptor binding and in an inhibition of ADCC and CDC. See ¶¶ 0021. Hoffman teaches that the reduced ADCC and CDC would lead to reduced antibody toxicity. See ¶¶ 069-0391.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of Robblee and Hoffman and delete the amino acid at position 329 of the Fc region of trastuzumab because Hoffman teaches that mutations like substitution and deletion of the amino acid at position 329 of the Fc region can inhibit ADCC and CDC activity and reduce antibody toxicity. One would have been motivated to delete the amino acid at position 329 of the Fc region of trastuzumab to reduce toxic side effects of trastuzumab produced for treating a patient with trastuzumab.
Conclusion
9. No claims allowed.
10. Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER J REDDIG whose telephone number is (571)272-9031. The examiner can normally be reached M-F 8:30-5:30 Eastern Time.
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, Greg Emch can be reached at 571-272-8149. 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.
/PETER J REDDIG/Primary Examiner, Art Unit 1646
APPENDIX
Alignment of SEQ ID NO: 2 with SEQ ID NO: 42 of Hoffman
Title: US-18-558-655-2
Perfect score: 2378
Sequence: 1 QVQLVQSGAEVKKPGSSVKV..........MHEALHNHYTQKSLSLSPGK 447
Scoring table: BLOSUM62
Gapop 10.0 , Gapext 0.5
Searched: 1 seqs, 227 residues
Total number of hits satisfying chosen parameters: 1
Minimum DB seq length: 0
Maximum DB seq length: inf
Post-processing: Minimum Match 0%
Maximum Match 100%
Listing first 50 summaries
Database : US-13-920-190-42.fasta:*
SUMMARIES
%
Result Query
No. Score Match Length DB ID Description
----------------------------------------------------------------------------
1 1209.5 50.9 227 1 US-13-920-190-42 INCRETIN RECEPTOR
ALIGNMENTS
RESULT 1
US-13-920-190-42
Query Match 50.9%; Score 1209.5; DB 1; Length 227;
Best Local Similarity 98.7%;
Matches 224; Conservative 2; Mismatches 0; Indels 1; Gaps 1;
Qy 222 DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVD 281
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVD 60
Qy 282 GVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL-APIEKTISKAK 340
|||||||||||||||||||||||||||||||||||||||||||||||| |||||||||||
Db 61 GVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK 120
Qy 341 GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS 400
|||||||||||||||:|:||||||||||||||||||||||||||||||||||||||||||
Db 121 GQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS 180
Qy 401 DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 447
|||||||||||||||||||||||||||||||||||||||||||||||
Db 181 DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 227
Alignment of SEQ ID NO: 27 with SEQ ID NO: 1 of Robblee
ALIGNMENT:
Query Match 99.6%; Score 2394.5; Length 450;
Best Local Similarity 99.8%;
Matches 449; Conservative 0; Mismatches 0; Indels 1; Gaps 1;
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRY 60
Qy 61 ADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSS 120
Qy 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
Qy 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG 240
Qy 241 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 300
Qy 301 STYRVVSVLTVLHQDWLNGKEYKCKVSNKAL-APIEKTISKAKGQPREPQVYTLPPSREE 359
||||||||||||||||||||||||||||||| ||||||||||||||||||||||||||||
Db 301 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 360
Qy 360 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 419
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 420
Qy 420 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 449
||||||||||||||||||||||||||||||
Db 421 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 450
Alignment of SEQ ID NO: 34 with SEQ ID NO: 2 of Robblee
ALIGNMENT:
Query Match 100.0%; Score 1110; Length 214;
Best Local Similarity 100.0%;
Matches 214; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPS 60
Qy 61 RFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPP 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPP 120
Qy 121 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 180
Qy 181 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 214
||||||||||||||||||||||||||||||||||
Db 181 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 214
Prosecution Insights