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 .
DETAILED ACTION
2. The election filed 10/24/2025 in response to the Office Action of 06/25/2025 is acknowledged and has been entered.
Applicant has elected Group I, claims 1-10, 12-15 and 18-21, drawn to an immuno-suppression refractory protein or polypeptide comprising the amino acid residue sequence of SEQ ID NO: 3, wherein one, two, or three amino acid residues in said sequence are substituted with an amino acid residue different than shown in SEQ ID NO: 3, wherein the one, two, or three substituted amino acid residues reduce or eliminate binding of the immuno-suppression refractory protein or polypeptide to an immuno-suppressive protein, relative to the immuno-suppression refractory protein or polypeptide without the one, two, or three amino acid substitutions.
Additionally, Applicant has elected an antibody containing a light chain according to SEQ ID NO: 6 and a heavy chain comprising SEQ ID: 8 as species of antibody.
Because applicant did not distinctly and specifically point out any supposed errors in the restriction requirement, the election has been treated as an election without traverse. See MPEP 818.03(a).
3. Claims 1-10, 12-15 and 18-21 are currently under prosecution.
Priority
4. Applicant’s claim under 35 U.S.C. §§ 119(e) and/or 365(c) for benefit of the earlier filing date of applications is acknowledged.
Improper Markush Grouping Rejection
5. Claim 5 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 § 706.03(y).
The Markush grouping of antibodies recited in claim 5 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: because the antibodies do not share a “single structural similarity”.
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.
Claim Rejections - 35 USC § 112
6. 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.
7. 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 12 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 pre-AIA the applicant regards as the invention.
Claim 12 is indefinite because claim 12 recites “the amino acid residue sequence of SEQ ID NO: 3 for CD20”. This recitation renders the claims indefinite because it is unclear what it means. Is “the amino acid residue sequence of SEQ ID NO: 3 binds to CD20, or the amino acid residue sequence of SEQ ID NO: 3 of CD20”? It is submitted that the claim cannot be unambiguously construed and therefore fail to delineate the metes and bounds of the subject matter that is regarded as the invention with the requisite clarity and particularity to permit the skilled artisan to know or determine infringing subject matter.
9. The following is a quotation 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.
10. The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
11. Claims 1-4, 6-8, 10, 12-15 and 18-21 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
This is a “written description” rejection.
The considerations that are made in determining whether a claimed invention is supported by an adequate written description are outlined by the published Guidelines for Examination of Patent Applications Under the 35 U.S.C. 112, para. 1, ``Written Description'' Requirement (Federal Register; Vol. 66, No. 4, January 5, 2001; The 2015 Written Description Workshop materials; hereinafter “Guidelines”).
These guidelines state that rejection of a claim for lack of written description, where the claim recites the language of an original claim should be rare. Nevertheless, these guidelines further state, “the issue of a lack of written description may arise even for an original claim when an aspect of the claimed invention has not been described with sufficient particularity such that one skilled in the art would recognize that the applicant has possession of the claimed invention” (Id. at 1105). The “Guidelines” continue:
The claimed invention as a whole may not be adequately described if the claims require an essential or critical feature which is not adequately described in the specification and which is not conventional in the art or known to one of ordinary skill in the art. This problem may arise where an invention is described solely in terms of a method of its making coupled with its function and there is no described or art-recognized correlation or relationship between the structure of the invention and its function. A lack of adequate written description issue also arises if the knowledge and level of skill in the art would not permit one skilled in the art to immediately envisage the product claimed from the disclosed process.
With further regard to the proposition that, as original claims, the claims themselves provide in haec verba support sufficient to satisfy the written description requirement, the Federal Circuit has explained that in ipsis verbis support for the claims in the specification does not per se establish compliance with the written description requirement:
Even if a claim is supported by the specification, the language of the specification, to the extent possible, must describe the claimed invention so that one skilled in the art can recognize what is claimed. The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement. The disclosure must allow one skilled in the art to visualize or recognize the identity of the subject matter purportedly described. Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997). See also: University of Rochester v. G.D. Searle & Co., 69 USPQ2d 1886 1892 (CA FC 2004).
Thus, an original claim may provide written description for itself, but it must still be an adequate written description, which establishes that the inventor was in possession of the invention.
Claims are drawn to a polypeptide comprising one, two, or three amino acid residues of SEQ ID NO: 3 are substituted.
In this instance, the claims are directed to a genus of polypeptide comprising one, two, or three amino acid residues of SEQ ID NO: 3 are substituted. Thus, claims encompass a genus of structural variants of the polypeptide SEQ ID NO: 3, which need not have or retain the specific activity or function of the polypeptide of SEQ ID NO: 3.
Given the fact that the claims are drawn to a genus of structural variants of the polypeptide SEQ ID NO: 3, which have no particular function or activity, there is no correlation between any one particularly identifying structural feature and any one particularly identifying functional feature. Consequently, it is submitted that the skilled artisan could not immediately envision, recognize or distinguish at least a substantial number of the polypeptides to which the claims are directed.
Although the specification SEQ ID NO: 3, SEQ ID NO: 3 is not reasonably representative of the plurality of structural variants of the polypeptide SEQ ID NO: 3. This is largely because the polypeptides have substantially varied structures and need not have any particular function or activity.
Guidelines states, “[p]ossession may be shown in a variety of ways including description of an actual reduction to practice, or by showing the invention was ‘ready for patenting’ such as by disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention” (Id. at 1104). “Guidelines” further states, “[f]or inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus” (Id. at 1106); accordingly, it follows that an adequate written description of a genus cannot be achieved in the absence of a disclosure of at least one species within the genus. Moreover, because the claims encompass a genus of structural variants of the polypeptide SEQ ID NO: 3, which vary both structurally and functionally, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. In this instance, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; Applicant has not shown the invention was “ready for patenting” by disclosure of drawings or structural chemical formulas that show that the invention was complete; and Applicant has not described distinguishing identifying characteristics sufficient to show that Applicant was in possession of the claimed invention at the time the application was filed.
Turning to a different issue, claims 18-21 are drawn to a method to treat a patient with a disease. However, the specification does not provide any data for treating a patient with a disease.
One ordinarily skilled in the art knows that each disease is an etiologically and/or pathologically distinct disease. Thus, there is no one particularly identifying etiologically and/or pathologically feature that is shared by the members of the genus of disease and any one particularly identifying etiologically and/or pathologically feature that is also shared by at least most of its members, which might permit the skilled artisan to immediately envision, recognize or distinguish at least a substantial number of the disease to which the claims refer.
It is well known that therapeutic art for treating patient is highly unpredictable. Given the unpredictability of therapeutic art and the teachings of the specification, it is clear that it is not possible to predictably extrapolate the claimed invention. Therefore, it is submitted that the claimed treating a patient with a disease is not adequately described with the requisite clarity and particularity to reasonably convey to the skilled artisan that Applicant had possession of the claimed invention as of the filing date of the application.
The Federal Circuit has decided that a patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated. See Noelle v. Lederman, 69 USPQ2d 1508 1514 (CA FC 2004) (citing Enzo Biochem II, 323 F.3d at 965; Regents, 119 F.3d at 1568).
Thus, it is submitted that the instant claims, and the disclosure describing the claimed subject matter, fails to satisfy the written description requirement set forth under 35 U.S.C. § 112, first paragraph.
12. 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 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.
Claim Rejections - 35 USC § 102
13. 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.
14. Claims 1-2, 5-10, 12-15 and 18-21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wilton et al. (US 20140004037, published on 01/02/2014, IDS).
Claims 1-2, 5-10, 12-15 and 18-21 are herein drawn to a polypeptide comprising the amino acid residue sequence of SEQ ID NO: 3, wherein one, two, or three amino acid residues in said sequence are substituted with an amino acid residue different than shown in SEQ ID NO: 3.
The instant specification teaches SEQ ID NO: 3 (residues of rituximab heavy chain); see [0145] of published application.
Wilton et al. teach the heavy chain (SEQ ID NO: 2) sequences of Rituximab, and a variant comprising SEQ ID NO: 2 with one or more of amino acid sequence changes (e.g., N109D); see entire document, e.g., [0005], [0034-0044], Tables 6 and 9.
SEQ ID NO: 2 of Wilton et al. is 100% identical with the instant claimed SEQ ID NO: 3; see below sequence alignment 1.
Although Wilton et al. do not expressly state that the anti-CD20 antibody is an immuno-suppression refractory protein; given that the product of prior art (variants of SEQ ID NO: 2) is structurally indistinguishable from the claimed product (variants of SEQ ID NO: 3), it is expected to have the same function (an immuno-suppression refractory protein). This is because the product of the prior art is materially and manipulatively indistinguishable from the claimed product. Therefore, absent a showing of any difference, the product of the prior art is deemed the same as claimed product. Notably, the Office does not have the resources and facilities for examining and comparing Applicant's product with the product of the prior art in order to establish that the product of the prior art does not have the same effects as the claimed product. In the absence of evidence to the contrary, the burden is upon the applicant to prove that the claimed product is different than that taught by the prior art. See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA, 1977) and Ex parte Gray, 10 USPQ2d 1922 1923 (PTO Board of Patent Appeals and Interferences, 1988 and 1989).
For claim 2, Wilton et al. teach the anti-CD20 antibody (Rituximab) is a full-length antibody; see [0034-0044].
For claims 5 and 9, Wilton et al. teach N109D mutation of Rituximab (see [0005]), which is the same as the instant claimed SEQ ID NO: 8; see below sequence alignment 2.
For claims 6-8, Wilton et al. teach the antibody is an IgG isotype antibody, and Fab; see [0050].
For claims 10 and 12, Wilton et al. teach affinity of site-specific mutations of anti-CD20 antibody; see Example 1.
For claim 13, Wilton et al. teach that Asp109 is positioned at the base of HC-CDR3; see Table 8.
For claim 14, Wilton et al. teach A113Q mutation which is in framework region 4; see [0005].
For claim 15, Wilton et al. teach that isolated nucleic acid vector encoding immunoglobulin heavy or light chains, or both, which comprise the anti-CD20 antibody; see [0006].
For claims 18-21, Wilton et al. teach a method of treating diseases in patients comprising administering to the patient a therapeutically effective amounts of the anti-CD20 antibody, wherein the disease is Non-Hodgkin's lymphoma, or rheumatoid arthritis; see [0008].
Conclusion
15. No claim is allowed.
16. Any inquiry concerning this communication or earlier communications from the examiner should be directed to YAN XIAO whose telephone number is (571)270-3578. The examiner can normally be reached M-F 8-5 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached on 571-270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/YAN XIAO/Primary Examiner, Art Unit 1642
Sequence alignment 1
US-13-354-123-2
Filing date in PALM: 2012-01-19
Sequence 2, US/13354123
Publication No. US20140004037A1
GENERAL INFORMATION
APPLICANT: WILTON, Rosemarie
TITLE OF INVENTION: STABILIZATION OF THE ANTI-CD20 ANTIBODY RITUXIMAB
FILE REFERENCE: 709569
CURRENT APPLICATION NUMBER: US/13/354,123
CURRENT FILING DATE: 2012-01-19
NUMBER OF SEQ ID NOS: 4
SEQ ID NO 2
LENGTH: 451
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Anti-CD20 Antibody Wild Type Heavy Chain Amino Acid Sequence, Rituximab HC
Query Match 100.0%; Score 759; Length 451;
Best Local Similarity 100.0%;
Matches 141; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 AVYYCARSTYYGGDWYFNVWGAGTTVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVK 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 92 AVYYCARSTYYGGDWYFNVWGAGTTVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVK 151
Qy 61 DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 152 DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS 211
Qy 121 NTKVDKKVEPKSCDKTHTCPP 141
|||||||||||||||||||||
Db 212 NTKVDKKVEPKSCDKTHTCPP 232
Sequence alignment 2
US-13-354-123-2
Filing date in PALM: 2012-01-19
Sequence 2, US/13354123
Publication No. US20140004037A1
GENERAL INFORMATION
APPLICANT: WILTON, Rosemarie
TITLE OF INVENTION: STABILIZATION OF THE ANTI-CD20 ANTIBODY RITUXIMAB
FILE REFERENCE: 709569
CURRENT APPLICATION NUMBER: US/13/354,123
CURRENT FILING DATE: 2012-01-19
NUMBER OF SEQ ID NOS: 4
SEQ ID NO 2
LENGTH: 451
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Anti-CD20 Antibody Wild Type Heavy Chain Amino Acid Sequence, Rituximab HC
Query Match 99.8%; Score 2413; Length 451;
Best Local Similarity 99.8%;
Matches 450; Conservative 1; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLQQPGAELVKPGASVKMSCKASGYTFTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLQQPGAELVKPGASVKMSCKASGYTFTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSY 60
Qy 61 NQKFKGKATLTADKSSSTAYMQLSSLTSEDSAVYYCARSTYYGGDWYFDVWGAGTTVTVS 120
||||||||||||||||||||||||||||||||||||||||||||||||:|||||||||||
Db 61 NQKFKGKATLTADKSSSTAYMQLSSLTSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVS 120
Qy 121 AASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 AASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQS 180
Qy 181 SGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLG 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 SGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLG 240
Qy 241 GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY 300
Qy 301 NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRD 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRD 360
Qy 361 ELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 ELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR 420
Qy 421 WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 451
|||||||||||||||||||||||||||||||
Db 421 WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 451