Prior art — US Patent 7364736B2

To identify the most relevant prior art for US patent 7364736B2, I have reviewed the patent text for embedded citations to other patents and published applications. The core of US7364736B2 describes antibodies to osteoprotegerin ligand (OPGL), specifically a fully human monoclonal antibody named αOPGL-1, defined by its heavy chain (SEQ ID NO: 2) and light chain (SEQ ID NO: 4) amino acid sequences, and their variable regions (SEQ ID NO: 13 and SEQ ID NO: 14). The patent also claims fragments, pharmaceutical compositions, and methods of treatment using these antibodies.

For the purpose of identifying "most relevant prior art" under 35 U.S.C. § 102, I will focus on patent citations that teach general methods for producing human or humanized antibodies, or specific antibody fragments, as these are foundational to the claimed invention. Direct anticipation of the specific amino acid sequences of αOPGL-1 (Claims 1, 7, 12, etc.) by these general method patents is highly unlikely, as anticipation requires every element of a claim to be disclosed, either explicitly or inherently, in a single prior art reference. However, these references may anticipate broader claims related to the method of making such antibodies or the form of the antibodies (e.g., single-chain antibodies).

Below are analyses of selected relevant patent citations from US7364736B2:

1. International Publication WO 93/12227

Full Citation: WO 1993/012227 A1.
Publication/Filing Date: Published: June 24, 1993. Filed: December 10, 1992.
Brief Description: This international publication describes transgenic non-human animals, particularly mice, that are genetically engineered to produce human antibodies in response to antigen challenge. These animals contain human immunoglobulin loci and are capable of producing a diverse repertoire of human antibodies. The methods involve the inactivation of endogenous immunoglobulin gene loci and the introduction of human immunoglobulin gene arrays.
Potential Anticipation (35 U.S.C. § 102):
- This publication potentially anticipates the method of producing human antibodies as generally described in the background of US7364736B2, particularly the concept of using transgenic animals to generate human antibodies. The patent US7364736B2 states, "antibodies of the invention are human antibodies prepared, for example, by immunization of transgenic animals capable of producing human antibodies (see, for example, PCT Published Application No. WO 93/12227)." While it doesn't anticipate the specific αOPGL-1 antibody sequences (Claims 1, 7, 12), it could anticipate a broader method claim for generating fully human antibodies if such a claim existed in US7364736B2 without the specificity to OPGL.
- It does not anticipate product claims (e.g., Claims 1, 7, 12) to the specific αOPGL-1 antibody or its sequences, nor the pharmaceutical composition claims (Claims 21, 22), nor the method of treatment claims (Claim 23), as it does not disclose antibodies specific to OPGL.

2. International Publication WO 98/24893

Full Citation: WO 1998/024893 A1.
Publication/Filing Date: Published: June 11, 1998. Filed: December 3, 1997.
Brief Description: This publication focuses on methods and compositions for generating diverse repertoires of human antibodies in non-human animals, such as transgenic mice. It describes the use of yeast artificial chromosomes (YACs) containing human immunoglobulin heavy and light chain gene loci to create transgenic animals capable of producing functional human antibodies. The mice are designed to be deficient in endogenous antibody production, ensuring the generation of human antibodies.
Potential Anticipation (35 U.S.C. § 102):
- Similar to WO 93/12227, this reference describes a fundamental method for generating fully human antibodies, which is explicitly mentioned as a technique that "one may employ" in US7364736B2 for producing its human antibodies. This reference could anticipate broad method claims for generating fully human antibodies, specifically those involving transgenic animals with human immunoglobulin loci.
- It does not anticipate the specific αOPGL-1 antibody (Claims 1, 7, 12), nor compositions (Claims 21, 22), nor treatment methods (Claim 23) of US7364736B2, as it does not disclose an antibody against OPGL or its specific sequences.

3. U.S. Patent 6,180,370

Full Citation: US 6,180,370 B1, "COMPLEMENTARITY DETERMINING REGION-GRAFTED ANTIBODIES HAVING REDUCED IMMUNOGENICITY AND ENHANCED AFFINITY," issued January 30, 2001.
Publication/Filing Date: Issued: January 30, 2001. Filed: June 16, 1998.
Brief Description: This patent describes methods for engineering complementarity determining region (CDR)-grafted antibodies. The invention provides CDR-grafted antibodies designed to reduce immunogenicity while maintaining or enhancing binding affinity, typically by grafting CDRs from a non-human antibody onto human framework regions. It also discloses specific methods for selecting framework region residues that are critical for antigen binding, thereby improving the humanization process.
Potential Anticipation (35 U.S.C. § 102):
- US7364736B2 mentions CDR grafting as a technique: "the complementarity determining regions (CDRs) of the light and heavy chain variable regions of αOPGL-1 may be grafted to framework regions (FRs) from the same, or another, species." This patent, US6180370, discloses the method of CDR grafting to create humanized antibodies. If US7364736B2 included a claim for a generic method of making a humanized antibody by CDR grafting, this patent could anticipate it.
- However, it does not anticipate claims specific to the αOPGL-1 antibody (Claims 1, 7, 12), nor compositions (Claims 21, 22), nor treatment methods (Claim 23), as it does not disclose antibodies against OPGL or its specific sequences. It teaches a method of antibody engineering, not the resulting specific product claimed in US7364736B2.

4. U.S. Patent 4,946,778

Full Citation: US 4,946,778 A, "SINGLE CHAIN ANTIBODIES," issued August 7, 1990.
Publication/Filing Date: Issued: August 7, 1990. Filed: April 25, 1988.
Brief Description: This patent describes recombinant DNA methods for producing single-chain antigen-binding proteins (single-chain antibodies, or scFv). These molecules consist of a heavy chain variable domain and a light chain variable domain, joined by a flexible polypeptide linker, forming a single polypeptide chain that retains antigen-binding specificity.
Potential Anticipation (35 U.S.C. § 102):
- US7364736B2 explicitly states, "Single-chain antibodies are Fv molecules in which the heavy and light chain variable regions have been connected by a flexible linker to form a single polypeptide chain which forms an antigen-binding region. Single chain antibodies are discussed in detail in WO 88/01649 and U.S. Pat. Nos. 4,946,778 and 5,260,203." US7364736B2 also claims "single chain antibodies" and "single chain Fv antibodies" (as stated in the definitions, implying they are also claimed). Therefore, US4946778 would anticipate any broad claim in US7364736B2 directed to a generic "single chain antibody" or "single chain Fv antibody" per se, without requiring specific binding to OPGL or the specific sequences of αOPGL-1.
- It does not anticipate claims specific to the αOPGL-1 antibody (Claims 1, 7, 12), nor compositions (Claims 21, 22), nor treatment methods (Claim 23), as it does not disclose antibodies against OPGL or its specific sequences. It anticipates the form of the antibody fragment, but not its target or specific sequence.

Summary of Relevance:
The prior art selected above (WO 93/12227, WO 98/24893, US 6,180,370, and US 4,946,778) are highly relevant to US7364736B2 because they disclose established methods and antibody formats (fully human antibodies via transgenic animals, CDR grafting, single-chain antibodies) that are explicitly mentioned or implicitly utilized in the context of the US7364736B2 invention. While these references generally do not anticipate the specific sequences of the αOPGL-1 antibody due to the high specificity required for 35 U.S.C. § 102, they could potentially anticipate broader claims related to the method of making human antibodies or the form of antibody fragments if such claims were drafted without the specific OPGL target and sequences.