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 .
Status of the claims
The Preliminary Amendment filed 12/10/24 is acknowledged and has been entered. Claims 3-15 have been amended. Currently, claims 1-15 are pending and under examination.
Information Disclosure Statement
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.
Specification
The use of the term Tween 20, which is a trade name or a mark used in commerce, has been noted in this application (e.g. page 28, lines 8-12). 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.
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
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.
Written Description
Claims 1-15 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.
The instant claims are directed to a method for determining avid-binding side-products of a bispecific antibody in a sample by use of SPR. The limitation 'avid-binding side-products of a bispecific antibody’ represents a genus and encompasses half antibodies, ¾ antibodies, mismatched light chain species, high molecular weight aggregates and low molecular weight fragments to name a few. However, there is inadequate written description in the instant specification for a method of such broad scope as claimed currently.
In order to fulfill the written description requirements set forth under 35 U.S.C § 112, first paragraph, the specification must describe at least a substantial number of the members of the claimed genus, or alternatively describe a representative member of the claimed genus, which shares a particularly defining feature common to at least a substantial number of the members of the claimed genus, each member correlated with the requisite function, which would enable the skilled artisan to immediately recognize and distinguish its members from others, so as to reasonably convey to the skilled artisan that Applicants have possession the claimed invention. Applicants have not described and established structure-function correlation for a representative number of species within the broad genus of at least the recited ‘avid-binding side-products’ such that the specification might reasonably convey to the skilled artisan that Applicants had possession of the full scope of the claimed invention at the time the application was filed.
The purpose of the written description requirement is ‘to ensure that the inventor had possession, as of the filing date of the application relied on, of the specific subject matter later claimed by him.’ In re Edwards, 568 F.2d 1349, 1351-52, 196 USPQ 465, 467 (CCPA 1978). Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895. A ‘representative number of species’ means that the species which are adequately described are representative of the entire genus. When there is substantial structural variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
A review of the instant specification indicates the following. The specification on page 6 discloses that the side product is a homodimeric antibody which is detecting by SPR. The specification on page 9, lines 25-32 discloses that the correctly assemble bispecific antibody is a heterodimer and the mis-assembled bispecific antibody is a homodimer. The specification on page 12 discloses that the current invention is directed to a method for determining homodimeric antibodies. The examples in the specification all appear to be directed to methods of detecting a homodimer antibody. The specification does not provide data, testing or examples with a showing that any all and all avid-binding side-products are detected by SPR or that any and all side-products provide the unique capability of comprising two or more binding sites to the first antigen and more binding sites to the first antigen than the correctly assembled bispecific antibody. As disclosed by the Applicant on page 2 SPR detection also constitutes a fundamental limitation: since every binding event causes a similar refractive index signal, it is not possible to discriminate different binding events resulting in similar mass changes. The current specification only provides for a homodimer antibody which allows for a determination by SPR and does not provide evidence or data for any and all avid-binding side-products. The only examples utilized in the specification appears to be limited to a homodimeric antibody of the bispecific antibody. The purpose of the ‘written description; requirement is broader than to merely explain how to ‘make and use’, Applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention.
It must be noted that "[t]he applicant must . . . convey to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention." Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64 (Fed. Cir.1991). The invention, is for purposes of the ‘written description’ inquiry, whatever is now claimed.” See page 1117. The specification does not describe the claimed embodiments in sufficient detail to convey to a person skilled in the art that Applicants were in possession of the full scope of the claimed invention at the time of filing. The Written Description Guidelines state: There is an inverse correlation between the level of predictability in the art and the amount of disclosure necessary to satisfy the written description requirement. For example, if there is a well-established correlation between the structure and function in the art, one skilled in the art will be able to reasonably predict the complete structure of the claimed invention from its function. Furthermore, the written description provision of 35 U.S.C § 112 is severable from its enablement provision; and adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. The Guidelines for Examination of Patent Applications Under the 35 U.S.C. 112, paragraph 1, ‘Written Description’ Requirement (66 FIR 1099-1111, January 5,2001) state, ‘[p]ossession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that 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). Moreover, because the claims encompass a genus of variant species, 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. Factual evidence of an actual reduction to practice has not been disclosed in the instant specification, nor has Applicant shown the invention was ‘ready for patenting’. The Guidelines further state, ‘[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). For inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession. Instant claims are viewed as not meeting the written description provision of 35 U.S.C § 112, first paragraph. The specification fails to disclose the detection of any and all avid-binding side-products of a bispecific antibody by the use of SPR and correctly assembled bispecific antibodies.
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 1-15 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1, line 1 the recitation “avid-binding side products” is vague and indefinite because the specification does not provide a definition for the term and the term is not a well know art recognized phrase. No examples of the phrase could be found by the Examiner. Thus, it is unclear what the term encompasses and the metes and bounds of the claim cannot be ascertained. It is recommended but not required to change the “avid-binding side-products” to --a homodimer antibody--.
Claim 14 the recitation “antibody-related homodimeric..” is vague and indefinite. The specification does not provide a definition for the term and it is unclear what the term encompasses. The claim does not make clear how the side-product is related to an antibody. The claim fails to make clear if the applicant intends a property or characteristic of an antibody or if the Applicant intends something else. Please clarify.
Claim 15 the recitation “antibody-related homodimeric..” is vague and indefinite. The specification does not provide a definition for the term and it is unclear what the term encompasses. The claim does not make clear how the side-product is related to an antibody. The claim fails to make clear if the applicant intends a property or characteristic of an antibody or if the Applicant intends something else. Please clarify.
Allowable Subject Matter
Claims 1-15 would be allowable if rewritten or amended to overcome the rejection(s) under 35 U.S.C. 112(a), and 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action. Pippig et al (WO 2020/200941) (submitted in the IDS filed 12/10/24) is considered to be the closest prior art of record. Pippig et al discloses a method to assess the purity of a sample comprising a bispecific antibody with the use of SPR (e.g. page 34). However, Pippig et al does not teach nor suggest i) applying a sample solution suspected to comprise an avid-binding side-product of the bispecific antibody to an SPR surface on which the first antigen has been immobilized with at least 1000 RU to generate an SPR signal, applying thereafter a dissolution solution not comprising a compound binding to the first antigen to the SPR chip and recording the decay of the SPR signal,iii) determining the avid-binding side-product of the bispecific antibody if the decay of the SPR signal determined in step ii) is slower than the decay of the SPR signal determined in step i).
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Reinartz et al (Analyst, June, 1996, Vol. 121, pages 767-771) discloses the study of bispecific antibodies b real-time analysis.
Meschendoerfer et al (Jornal of Pharmaceutical and Biomedical Analysis, 132, 2017, pages 141-147) discloses the detection of bispecific antibodies with SPR (e.g. page 141).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GARY W COUNTS whose telephone number is (571)272-0817. The examiner can normally be reached M-F 7:00-4:00.
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/GARY COUNTS/ Primary Examiner, Art Unit 1678
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