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 09/08/2023, is acknowledged.
3. Claims 1-20 are pending.
4. Claims 1-20 are objected to for the following reasons
(i) claims 1-3(h)-(i) SEQ ID NOs:71-76 (CDB312) are identical to SEQ ID NOs: 81-86 (CD9B312m1).
(ii) Claims 1-3(J) and (K) SEQ ID NO: 91-96 (CD9B292) are identical to SEID NO: 101-106 (CD9B292m1).
(iii) Claim 2(a)-(b) SEQ ID NO: 4-6 are identical to SEQ ID NO: 14-16,
(iv) SEQ ID NO: 28, 58 and 38, 68, respectively, are identical.
Applicant is required to check the rest of the sequence to make sure that the claims are do not recite identical limitations having identical claim scope.
5. For clarity reasons, it is suggested that the preamble of the claims be changed to “an isolated antibody or antigen binding fragment thereof that specifically binds . . .”
6. The following is a quotation of 35 U.S.C. 112(a) (Pre-AIA 35 U.S.C. 112, first paragraph):
(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.
7. Claims 1-2, 4-5, 7-10, 13-20 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.
Claims 1-2, 4, 5, 7-10 encompass a broad genus of anti-CD79b antibodies comprising less than the required 6 CDRs.
However, there does not appear to be an adequate written description in the specification as-filed of the essential structural feature that provides the recited function of binding CD79b, treating or preventing an autoimmune disease and modulating B cell activation or inhibiting aberrant B cell activation. The Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, ¶ 1 "Written Description" Requirement make clear that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the genus.
The specification discloses 14 anti-CD79b antibodies: CD9B366/ m1, CD9B376/ m1, CD9B378, CD9B164/ m1, CD9B312/ m1, CD9B292/ m1, CD9B1256, CD9B1218 and CD9B1315; which were not random combinations of VH and VL i.e., they had specific VH domain (SEQ ID NO: 7,17, 27, 37, 47, 57, 67, 77, 87, 97, 107, 117, 127, 137) paired with specific VL domain (SEQ ID NO:8, 18, 28, 38, 38, 48, 58, 68, 78, 88, 98, 108, 118, 128, 138, respectively). No other VH or VL domain was provided that binds to CD79b. The specification discloses only 14 species within the instant claim scope. The instant application encompasses (but does not exemplify) 3 VH or VL CDRs modification that binds CD79b. Neither the specification nor the prior art provide VH-CDRs or VL-CDRs capable of binding CD79b. The state of the prior art is such that it is well established in the art that the formation of an intact antigen-binding site of antibodies routinely requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs or hypervariable regions, which provide the majority of the contact residues for the binding of the antibody to its target epitope (Paul, Fundamental Immunology, 3rd Edition, 1993, pp. 292-295, under the heading "Fv Structure and Diversity in Three Dimensions" of record). 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 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 an antibody 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 (Paul, page 293, first column, lines 3-8 and line 31 to column 2, line 9 and lines 27-30). 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 as evidenced by Rudikoff et al (Proc. Natl. Acad. Sci. USA, 79(6):1979-1983, March 1982 (of record)). Rudikoff et al teach that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function.
Neither the specification, nor the prior art provides any examples to support the premise of either the a HCDR or LCDR of the VH/VL would result in antigen binding.
With respect to the recitation an antibody which does not comprise all 6 CDRs of the antibody that is produced by CD9B366/ m1, CD9B376/ m1, CD9B378, CD9B164/ m1, CD9B312/ m1, CD9B292/ m1, CD9B1256, CD9B1218 and CD9B1315, the Examiner directs Applicant's attention to the training material given by Bennett Celsa, Example 2: (Ab genus: modified CDR's) slides 34-40. Example 2 of the Training material which requires that the claims explicitly recite the binding antigen in addition to all 6 CDR regions for fulfillment of the written description requirements under § 112, 1. Slide 39 indicates that a claim encompasses antibodies with 6 intact CDRs as well as a subgenus of antibodies that encompass up to 10% variation (fragments and/or analogs) in the 6 CDRs lacks written description. Slide 40 provide the conclusion that, a single antibody species would not be deemed by one of skill in the art to be representative of a claim that defines an antibody that binds antigen X comprising at least 90% homology to the 6 CDR of the VH and VL chains.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that “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. The invention is, for purposes of the written description inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116.). Consequently, Applicant was not in possession of the instant claimed invention. See University of California v. Eli Lilly and Co. 43 USPQ2d 1398.
Applicant is invited to point to clear support or specific examples of the claimed invention in the specification as-filed.
8. Claims 18-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as containing 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.
The specification does not reasonably provide enablement for methods of treating or preventing an autoimmune disease in a subject comprising administering the claimed CD79b antibodies; wherein the autoimmune disease is Systemic lupus erythematosus (SLE), Sjogren's syndrome (SjS), Rheumatoid arthritis, Autoimmune myopathies, Type I diabetes, Addison disease, Pernicious anemia, Autoimmune hepatitis, Primary biliary cholangitis (PBC), Autoimmune pancreatitis, Celiac disease, Focal segmental glomerulosclerosis, Primary membranous nephropathy, Ovarian insufficiency, Autoimmune orchitis, Dry eye disease, Idiopathic interstitial pneumonias, Thyroid disease (eg Grave's), Systemic sclerosis (Scleroderma), Myasthenic syndromes, Autoimmune Preliminary Amendment encephalitis, Bullous skin diseases, TTP, ITP, AIHA, Anca vasculitis, Myocarditis/dilatory CM, NMOSD, Maternal-fetal alloimmunity, Maternal-fetal autoimmunity, Anti- cardiolipin/antiphospholipid syndrome, Hypergammaglobulinemia, Transplant-associated ID, Multifocal motor neuropathy; methods of modulating B cell activation or inhibiting aberrant B cell activation in a subject comprising administering the claimed CD79b antibodies. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The claims are directed to the treatment of a broad genus of diseases including each and every autoimmune disease with the claimed anti-CD79b antibodies.
The specification does not provide empirical data to show the efficacy of the claimed anti-CD79b antibodies on any disease. No working empirical data demonstrating that the anti-CD79b antibody would treat autoimmune disease including Systemic lupus erythematosus (SLE), Sjogren's syndrome (SjS), Rheumatoid arthritis, Autoimmune myopathies, Type I diabetes, Addison disease, Pernicious anemia, Autoimmune hepatitis, Primary biliary cholangitis (PBC), Autoimmune pancreatitis, Celiac disease, Focal segmental glomerulosclerosis, Primary membranous nephropathy, Ovarian insufficiency, Autoimmune orchitis, Dry eye disease, Idiopathic interstitial pneumonias, Thyroid disease (eg Grave's), Systemic sclerosis (Scleroderma), Myasthenic syndromes, Autoimmune Preliminary Amendment encephalitis, Bullous skin diseases, TTP, ITP, AIHA, Anca vasculitis, Myocarditis/dilatory CM, NMOSD, Maternal-fetal alloimmunity, Maternal-fetal autoimmunity, Anti- cardiolipin/antiphospholipid syndrome, Hypergammaglobulinemia, Transplant-associated ID, Multifocal motor neuropathy.
Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized In re Wands (858 F2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)). The factors most relevant to this rejection are the scope of the claim, the amount of direction or guidance provided, the lack of sufficient working examples, the unpredictability in the art and the amount of experimentation required to enable one of skill in the art to practice the claimed invention.
The specification disclosure does not enable one skilled in the art to practice the invention
without an undue amount of experimentation. The specification lacks empirical data on the in vitro or in vivo efficacy of claimed anti-CD79b antibodies. It is noted that the specification
does not provide exemplification or animal model to treat a subject with anti-CD79b antibodies. There is no correlation on this record between the claimed anti-CD79b antibodies and a practical method of in vivo use in currently available form for subject suffering from autoimmune disease. It is not enough to rely on scientific theories where a person having ordinary skill in the art has no basis for perceiving those studies as constituting recognized screening procedures with clear relevance to methods of in vivo use in humans or animals. There must be a rigorous correlation of pharmacological activity between the disclosed in vitro use and an in vivo or ex vivo use to establish practical methods of in vivo use.
The influence of a scientific theory should depend on its empirical and demonstrable aspects and not its underlying logic. Yet such empirical and demonstrable aspects of the claimed methods with the anti-CD79b antibodies are lacked in the instant specification. It is not
clear that the skilled artisan could predict the efficacy of the anti-CD79 antibodies,
encompassed by the claims. The specification fails to provide empirical data to show that the
claimed method would work in vivo.
The burden of enabling the prevention of a disease (i.e. the need for additional testing) would be greater than that of enabling a treatment due to the need to screen those mammals susceptible to such diseases and the difficulty of proof that the administration of the drug was the agent that acted to prevent the condition. Further, the specification does not provide guidance as to how one skilled in the art would go about screening those patients susceptible to diabetic retinopathy within the scope of the presently claimed invention. Nor is sufficient guidance provided as to a specific protocol to be utilized in order to prove the efficacy of the presently claimed anti-CD79b antibody in preventing autoimmune disease.
The MPEP states that the issue of "correlation" is dependent on the state of the prior art. In other
words, if the art is such that a particular model is recognized as correlating to a specific condition, then it should be accepted as correlating unless the examiner has evidence that the
model does not correlate. Even with such evidence, the examiner must weigh the evidence for and against correlation and decide whether one skilled in the art would accept the model as reasonably correlating to the condition. See MPEP 2164.02.
In re Fisher, 166 USPQ 18 indicates that the more unpredictable an area is, the more specific
enablement is necessary in order to satisfy the statute. One cannot extrapolate the teachings of
the specification to the scope of the claims because the method claims are drawn to treating
autoimmune diseases using the claimed anti-CD79b antibodies. No working empirical data demonstrating that claimed anti-CD79b antibodies would be use in the claimed methods. The specification lacks empirical data on the in vivo efficacy of claimed anti-CD79b antibodies on subjects including human. The experiments in the specification never successfully used anti-CD79b antibodies in treating and preventing autoimmune diseases. Based on the absence of a specific and detailed description in Applicant's specification of how to effectively use the methods as claimed, and absence of working examples providing evidence which is reasonably predictive that the claimed methods are effective for treating autoimmune diseases in a subject, and the lack of predictability in the art at the time the invention was made, an undue amount of experimentation would be required to practice the claimed methods with a reasonable expectation of success. There is no evidence of record that demonstrates that the anti-CD79b antibodies can be used to treat and prevent autoimmune diseases. The specification fails to provide working examples providing evidence which is reasonably predictive that the claimed methods are effective for the prevention and treatment of autoimmune disease. The lack of any
working examples is exacerbated because the invention is in a highly unpredictable art- autoimmune disease - and while the level of skill of in the art may be high, the state of the prior art is that it is in fact unknown and untested what are the underlying molecule and physiologic bases of the therapeutic effects of anti-CD79b antibody in the treatment of autoimmune disease.
Moreover, if the use disclosed is of such nature that the art is unaware of successful treatments
with chemically analogous compounds, a more complete statement of how to use must be
supplied. The scope of the required enablement varies inversely with the degree of predictability
involved, but even in unpredictable arts, a disclosure of every operable species is not required. A
single embodiment may provide broad enablement in cases involving predictable factors, such as
mechanical or electrical elements...However, in applications directed to inventions in arts where
the results are unpredictable, the disclosure of a single species usually does not provide an
adequate basis to support generic claims.” MPEP § 2164.03. "First, although appellants'
specification describes certain in vitro experiments, there is no correlation on this record between
in vitro experiments and a practical utility in currently available form for human or animal
subjects. It is not enough to rely on in vitro studies where, as here, a person having ordinary skill
in the art has no basis for perceiving those studies as constituting recognized screening
procedures with clear relevance to utility in humans or animals" (emphasis added). Ex parte
Maas, 9 USPQ2d 1746.
Reasonable correlation must exist between the scope of the claims and scope of the enablement set forth. In view on the quantity of experimentation necessary the limited working examples, the nature of the invention, the state of the prior art, the unpredictability of the art and the breadth of the claims, it would take undue trials and errors to practice the claimed invention.
9. Claims 3,6, 11-12 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
10 Any inquiry concerning this communication or earlier communications from the examiner should be directed to MAHER M HADDAD whose telephone number is (571)272-0845. The examiner can normally be reached on Monday-Friday from7:00AM to 4:30PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu, can be reached at telephone number 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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March 9, 2026
/MAHER M HADDAD/ Primary Examiner, Art Unit 1644