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
Applicant’s election without traverse of Group I in the reply filed on 10/20/2025 is acknowledged. Claims 33, 36, 49 and 50 are drawn to a different invention are withdrawn.
Applicant’s election of species of antibody which comprises heavy chain variable region of SEQ ID NO:43 (HC15) and light chain variable region of SEQ ID NO:42 (LC3) in the reply filed on 10/20/2025 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)). However, because the elected specie is free of the prior art and in the interest of compact prosecution, the restriction of species is withdrawn and all species are examined.
Claim Interpretation
Claims 2, 40 and 41-47 recite the name of an antibody heavy or light chain, e.g., HC1, followed by a sequence identifier within parentheses (see rejection under 35 USC 112(b) below). For the purpose of compact prosecution, the claims are being interpreted as requiring that the named antibody necessarily comprises the sequence recited in the claims.
Information Disclosure Statement
The IDS filed 06/05/2023 is a duplicate of the IDS filed 11/18/2022.
Specification
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed.
The following title is suggested: CD40 Antagonist Antibody Variants with Improved Pharmacokinetic Properties
The disclosure is objected to because of the following informalities: At the end of [00103] “100_)” should be “100)”. In row 1 of Table 24, “[Symbol font/0xFF]Chrg” is incorrect.
Appropriate correction is required.
The use of the term Agilent, Chemstation, ShowaDenko (paragraph [0211]), Gibco ([0216]) and GraphPad ([217]), which is a trade name or a mark 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.
Applicant is encouraged to carefully review the specification for additional uses of trade names or marks.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 48 rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 48 depends from cancelled claim 18. Additionally, claim 48 is drawn to “The method of claim…,” while there are no other method claims. Further, there is no previous recitation of a immunosuppressive, immunomodulatory, and/or anti-inflammatory agent, so claim 48 cannot further limit the “said… agent”. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 112(b)
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 2, 40, 41-48 and dependent claims 4, 12, 13 and 37 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.
Claims 2, 40, 41-47 are indefinite because they recite the name of an antibody heavy or light chain, e.g., HC1, followed by a sequence identifier within parentheses. It is unclear whether the limitation in parentheses (i.e., the SEQ ID NO:) following the name is a required part of the claimed invention. It is suggested that if it is, the position of the name and SEQ ID NO: be reversed, that is, that the SEQ ID NO: precede the name in parentheses, e.g., SEQ ID NO:40 (HC1).
Claim 40 recites “said heavy chain variable region comprises”, and list SEQ ID NO:47, 86 or 49; however, these sequences have both the variable region and the heavy chain constant domain 1 (CH1) region (see Table 11). An antibody heavy chain variable region (VH) does not comprise a constant domain. The specification does say ([0083]), “[T]he carboxyl terminus of the variable domain may be linked or fused to the amino terminus of a CH1 domain….” The claim similarly recites “said light chain variable region comprises”, and lists SEQ ID NO:17, 19 or 20; however, these sequences have both the variable region and light chain constant domain (CL). An antibody light chain variable region (VL) does not comprise a constant domain.
Claim 41 is also indefinite for similar reasons. Namely, the SEQ ID NO: comprised by “said heavy chain variable region” (SEQ ID NO:35, 56, 84 or 85) and “said light chain variable region” (SEQ ID NO:17, 19 or 20), comprise more than the variable region. The heavy chain sequences are for the full heavy chain and the light chain sequences are for the full light chain. An antibody variable region does not comprise the hinge and/or constant domain(s) of the full antibody heavy or light chain.
These rejections could be obviated by instead of referring to “said heavy [or light] chain variable region”, for example, ‘said first polypeptide portion’ and ‘said second polypeptide portion’ comprising the respective recited sequences.
Claim 48 is indefinite because it is drawn to a method but has no active method steps.
Prior Art
The prior art made of record and not relied upon is considered pertinent to Applicant's disclosure.
US 11,261,258 B2 (cited in the IDS filed 2/17/2023) and the several other patents which have the same disclosure share Applicant and inventors with the instant application. It shows in Table 10 the sequence of variants of humanized anti-CD40 antibody Y12XX, including Y12XX-hz28. The instant specification states that antibody is also called BMS-986325 and is the antibody upon which the instantly claimed variants are based (([0049]). None of the anti-CD40 antibodies in the patent have the same variable heavy and light chains as the instantly claimed antibodies, though they may vary by a single amino acid. Nevertheless, neither the patent alone nor in combination with the prior art makes the particularly instantly claimed variants obvious. Indeed, the instant specification states in [0223] that, “These data are consistent with the hypothesis that the specific site or location of a mutation to modify a surface charge patch rather than just modifying the total antibody charge, is critical to improving antibody PK.” The data in the instant specification point to the particularity of the amino acids which are substituted and by with what amino acid they are substituted as important in improving the antibody’s pharmacokinetics. Note, BMS-986325 comprises the CDRs of humanized antibody Y12XX-hz28 (Vh-hz14; Vk-hz2) and a human IgG1 Fc domain comprising a lysine at Kabat position 238 (P238K).
WO 2020/106620 A1 (cited in the IDS filed 2/17/2023) has an earlier effective filing date than the instant application and discloses antibody Y12XX-hz28 (see immediately above; Vh-hzl4;Vk-hz2), Y12XX-hz40 (Vh-hzl2;Vk-hz3), and Y12XX-hz42 (Vh-hzl4;Vk-hz3). As with US 11,261,258 above, the sequences of the antibodies of the instant claims are neither disclosed in nor obvious over the antibodies disclosed in the WO document.
Leigold et al. (Clin. Transl. Sci. 12:130-139, 2019, cited in the IDS filed 2/17/2023) discusses antibody modifications to improve pharmacokinetics (PKs). Studies are discussed which improved antibody PK properties by changing the charge of patches of amino acids (p. 132, col. 2, third paragraph). It refers to Bumbaca et al. (J. Biol. Chem. 290:29732-29741, 2015, cited in the IDS filed 2/17/2023), which used an empirical approach based on the high resolution antigen-antibody complex structure available to design variants. While the prior art provides an invitation to try changing antibody protein charge to improve pharmacokinetics, it does not reasonably appear the number and placement of the amino acid changes would have been obvious to lead to the six particular antibody VH/VL pairs of independent claim 2.
Allowable Subject Matter
Claims 2, 40, 41-47 would be allowable if rewritten or amended to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action.
Claims 4, 12, 13 and 37 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Claire Kaufman, whose telephone number is (571) 272-0873. Examiner Kaufman can generally be reached Monday through Friday 7am-3:30pm, Eastern Time.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Vanessa Ford, can be reached at (571) 272-0857.
Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (571) 272-1600.
Official papers filed by fax should be directed to (571) 273-8300. NOTE: If applicant does submit a paper by fax, the original signed copy should be retained by the applicant or applicant's representative. NO DUPLICATE COPIES SHOULD BE SUBMITTED so as to avoid the processing of duplicate papers in the Office.
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Claire Kaufman
/Claire Kaufman/
Primary Examiner, Art Unit 1674
December 10, 2025